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Depression

Depression featured article

Depression is a neuropsychiatric disorder characterized by negative mood, loss of interest in doing things, and metabolic, hormonal, and immune disturbances that can degrade a person's quality of life and increase their risk of disease and death. The World Health Organization estimates that approximately 322 million people – more than 4 percent of the global population – currently live with depression, the most common mental health disorder worldwide. Between 2005 and 2015 (the most recent years for which robust meta-analyses are available), the number of people living with depression worldwide increased by more than 18 percent. It is estimated that only one-third of people struggling with depression receive treatment.

Clinicians diagnose depression as major depressive disorder based on a set of diagnostic criteria including one of two primary symptoms – depressed mood (e.g., sadness, irritability) and/or anhedonia (i.e., loss of interest or pleasure in...

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Episodes

intestinal permeability

Intestinal Permeability: the Bacterial link to Aging, Brain Barrier Dysfunction & Metabolic Disorder

Posted on May 30th 2022 (about 3 years)

Dr. Patrick's keynote: compromised intestinal barrier affects human health—cardiometabolic function, neurological health, behavior, and more.

sauna

Sauna Benefits Deep Dive and Optimal Use with Dr. Rhonda Patrick & MedCram

Posted on April 13th 2022 (about 3 years)

MedCram co-founder Kyle Allred discusses sauna's exercise mimetic, anti-inflammatory, mood-elevating, and detoxifying properties in this episode.

depression

Aerobic exercise alters tryptophan and kynurenine metabolism (beneficial for depression)

Posted on April 9th 2022 (about 3 years)

In this clip, Dr. Patrick explains how intense exercise beneficially alters tryptophan and kynurenine metabolism in a way that may benefit depression.

Topic Pages

  • Aerobic exercise

    Aerobic exercise mitigates depressive pathophysiology via hippocampal BDNF upregulation, monoaminergic enhancement, HPA-axis normalization, and anti-inflammatory cytokine shifts.

  • Berberine

    Preclinical studies indicate berberine alleviates depressive-like behaviors by inhibiting monoamine oxidase and upregulating BDNF/TrkB signaling.

  • Cold exposure

    Acute cold exposure elevates central norepinephrine and beta-endorphin, potentially ameliorating depressive states via augmented monoaminergic signalling.

  • Creatine

    Creatine augments brain phosphocreatine stores, enhancing ATP buffering and mitochondrial function, which can ameliorate bioenergetic deficits observed in depression.

  • Depression

    Major depressive disorder involves dysregulated monoaminergic neurotransmission, neuroinflammation, HPA-axis hyperactivity, and impaired neuroplasticity driving persistent low mood.

  • Omega-3 fatty acids

    Omega-3 EPA/DHA modulate neuronal membrane fluidity, monoaminergic receptor function, and inflammatory signaling, mechanisms hypothesized to alleviate depressive symptoms.

  • Red light therapy (photobiomodulation)

    Transcranial red-near-infrared photobiomodulation activates cortical cytochrome-c oxidase, boosting ATP and neurotrophic signaling, countering depressive pathology.

  • Sauna

    Sauna-induced whole-body hyperthermia may ameliorate depression by lowering pro-inflammatory cytokines and recalibrating hypothalamic-pituitary-adrenal stress responsiveness.

  • Whole-body hyperthermia

    Whole-body hyperthermia elevates core temperature, modulating peripheral cytokines and central serotonergic circuits, thereby attenuating depressive symptoms.

News & Publications

  • Chronic stress inhibits autophagy—the brain's recycling system—but restoring its functionality yields rapid antidepressant effects. pubmed.ncbi.nlm.nih.gov
    Brain Depression Stress Autophagy

    In small doses, stress can sharpen focus and improve resilience, but chronic stress gradually erodes emotional stability, increasing the risk of major depressive disorder. A recent study found that autophagy—the brain’s recycling and housekeeping system—helps maintain emotional stability by removing old or damaged proteins.

    Researchers explored how short-term and long-term stress influenced autophagy in mice and investigated whether antidepressant drugs could restore this process. Employing genetic techniques, the researchers selectively inhibited or enhanced autophagy in a region of the brain called the lateral habenula and then monitored how the animals reacted to stress.

    They found that acute stress activated autophagy, while chronic stress inhibited it. When autophagy ceased functioning properly, stress-related behaviors increased. However, restoring autophagy—even briefly—produced rapid antidepressant-like effects. Drugs commonly used to treat depression also reactivated autophagy in this brain region. Additional experiments indicated that autophagy helps regulate brain cell activity by breaking down excess glutamate receptors, which are often overactive in depression.

    These findings suggest that disrupted autophagy in the lateral habenula plays a central role in how chronic stress contributes to depression. Learn more about autophagy in this episode featuring Dr. Guido Kroemer.

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  • Anti-inflammatory treatments, particularly omega-3 fatty acids and plant-based compounds, effectively reduce depression symptoms in older adults. www.nature.com
    Omega-3 Inflammation Depression Mental Health NSAID Polyphenol

    Inflammation and depression are often linked, particularly in older adults, who tend to experience chronic low-grade inflammation and elevated rates of depression. A recent study found that anti-inflammatory interventions may help reduce symptoms of depression and the risk of developing depression in older adults.

    Researchers conducted a systematic review and meta-analysis of 31 randomized, placebo-controlled trials that assessed the effects of anti-inflammatory therapies on depression in older adults. The various anti-inflammatory agents included omega-3 fatty acids, nonsteroidal anti-inflammatory drugs, and plant-based compounds. The researchers included only trials with at least 20 participants.

    The analysis revealed that anti-inflammatory treatments were more effective than placebos in reducing depression symptoms among older adults. On average, people receiving these treatments exhibited a moderate improvement in symptom severity compared to those taking a placebo. Omega-3 fatty acids and plant-based compounds, such as curcumin and soy protein, appeared particularly beneficial. There was also some evidence suggesting that these treatments might help prevent depression, although the results were not statistically conclusive.

    These findings suggest that targeting inflammation is a promising strategy for managing depression in older adults, especially those with chronic inflammation. Learn more about links between inflammation and depression in Aliquot #36: Inflammation and Depression, part 2

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  • Misaligned sleep patterns and natural sleep preferences increase mental health risk, hinting at the crucial role of sleep timing and chronotype consistency for healthy aging. www.sciencedirect.com
    Sleep Depression Mental Health Anxiety

    The timing of when a person sleeps—not just how long—plays a vital role in mental health, influencing mood, cognitive function, and overall well-being. A recent study found that misalignment between bedtime and natural sleep preferences can increase the risk of mental health disorders like depression and anxiety.

    Researchers identified the chronotype—whether they were morning or evening types—of nearly 74,000 middle-aged and older adults enrolled in the UK Biobank. They tracked sleep patterns using accelerometry and evaluated their sleep and chronotype alignment. They assessed mental health outcomes through standard diagnostic codes.

    They found that morning types who went to bed late had a greater risk of mental health disorders, including depression and anxiety, than those whose sleep timing matched their chronotype. Interestingly, evening types who went to bed early had a lower risk of depression and a trend toward reduced risks of other mental health issues.

    These findings suggest a mismatch between one’s biological preferences and sleep schedule can harm mental well-being. The investigators posited that people should aim to sleep before 1 a.m. for optimal mental health, even if their natural chronotype favors later sleep. Learn more about chronotypes in this clip featuring Dr. Matthew Walker.

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  • Depression symptoms dropped markedly after one 25-milligram psilocybin dose in a study of people with severe treatment-resistant depression. psychiatryonline.org
    Depression Mental Health Drug Psychedelic

    People with severe treatment-resistant depression—those who don’t respond to five or more treatments—often struggle for years, cycling through medications and therapies that fail to provide relief. Standard treatments, including neuromodulation techniques like deep brain stimulation, have limited success and carry considerable risks. A recent study found that a single dose of psilocybin, a psychedelic compound found in certain mushrooms, provided rapid and lasting relief for people with treatment-resistant depression.

    Researchers conducted a 12-week, open-label trial involving 12 adults with severe treatment-resistant depression. Participants received a single 25-milligram dose of synthetic psilocybin and met with therapists before, during, and after the dosing session to help process their experiences. Using a standard depression symptom scale, researchers assessed changes in depression severity at three weeks, with additional assessments up to 12 weeks.

    By week three, the participants' depressive symptoms had dropped markedly, with an average reduction in severity of nearly 16 points on a standard scale. These improvements persisted through week 12. However, participants with post-traumatic stress disorder experienced less benefit, indicating that having more than one neuropsychiatric condition may influence treatment response.

    This was a small study, but the findings suggest that psilocybin, combined with psychological support, could be a powerful tool for people with severe treatment-resistant depression. Larger studies may yield more conclusive results. Learn more about psilocybin in this episode featuring the late Dr. Roland Griffiths.

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  • Repetitive transcranial magnetic stimulation, a non-invasive brain stimulation technique, shows promise in improving brain connectivity and aiding people with treatment-resistant depression. pubmed.ncbi.nlm.nih.gov
    Brain Depression

    Depression is a major public health concern, affecting more than 322 million people worldwide. A hallmark of depression involves reduced activity in specific brain areas and heightened activity in others, impairing brain connectivity. A recent study found that repetitive transcranial magnetic stimulation (TMS)—a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain—improved brain connectivity in people with treatment-resistant depression.

    The study involved 75 participants with treatment-resistant depression who underwent 20 treatment sessions over five consecutive days. Researchers randomly assigned them to three groups: a dual-target group receiving TMS to both sides of the brain, a single-target group, and a control group that received a sham treatment. Each session lasted 22 minutes, with functional magnetic resonance imaging conducted before and after treatment to assess changes in brain activity.

    They found that 47.8% of patients in the dual-target group responded favorably to treatment, compared to 18.2% in the single-target group and just 4.3% in the sham group. The active treatment demonstrated greater effectiveness at the four-week follow-up than the sham. Notably, many participants exhibited low baseline brain connectivity, and higher connectivity predicted better outcomes.

    These findings suggest that dual-target TMS promotes rapid and clinically significant improvements for people with treatment-resistant depression. Lifestyle behaviors, including sauna use and exercise, can help people with treatment-resistant depression, too. Learn more about the role of lifestyle in managing depression in our overview article.

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  • Psilocybin from 'magic' mushrooms offers comparable or enhanced depression relief over traditional SSRIs, improving social functioning and life meaning. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370\(24\)00378-X/fulltext
    Depression Mental Health Psychedelic

    Psilocybin, the active ingredient in “magic” mushrooms, is gaining attention for its potential to treat depression. Traditional treatments like selective serotonin reuptake inhibitors (SSRIs) have been widely used for years, but they carry many risks. A recent study found that psilocybin was comparable to or better than SSRIs in treating depression.

    Researchers assigned 59 people with moderate-to-severe depression to one of two groups. One group received two 25-milligram doses of psilocybin, and the other received a six-week course of escitalopram—a widely prescribed SSRI. Both groups received six months of psychological support. At the end of the trial, the researchers assessed the participants' depressive symptoms.

    They found that both groups experienced lasting reductions in depression severity over six months. However, participants in the psilocybin group had greater improvements in social functioning, connectedness, and life meaning than the escitalopram group.

    The findings from this small study bolster other research demonstrating the beneficial mental health effects of psilocybin. Psilocybin stimulates serotonin receptors in the brain, promoting mood, perception, and thought pattern changes, potentially reducing symptoms of depression. Learn more about psilocybin’s effects on depression in this episode featuring Dr. Rhonda Patrick.

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  • Older adults who used psychedelics exhibited better cognitive function and fewer depressive symptoms than non-users. journals.sagepub.com
    Aging Depression Mental Health Psychedelic

    Psychedelic drugs are hallucinogenic substances that alter cognition and perception, inducing visual and auditory changes and a “heightened state of consciousness.” They have a long history of traditional use in medicine and religion for their perceived ability to promote physical and mental health. A recent review found that older adults who have used psychedelic drugs tend to exhibit better cognitive functioning and fewer depressive symptoms than those who have not.

    The study involved more than 2,500 adults between the ages of 42 and 92. Researchers assessed participants' executive function and episodic memory and enquired about their use of psychedelic drugs, including marijuana, LSD, or other hallucinogens (e.g., PCP, angel dust, peyote, ecstasy, mescaline, or Prozac), in the previous 12 months.

    They found that participants who reported psychedelic use had better executive function but not episodic memory. They also tended to have fewer depressive symptoms.

    Psychedelic drugs primarily act on serotonin receptors, particularly the 5-HT2A receptor, altering perception, mood, and cognition. These changes in brain activity and connectivity may promote neuroplasticity, potentially benefiting overall cognitive function and mental health. Learn more about psychedelic drugs in this episode featuring Dr. Roland Griffiths.

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  • Psilocybin reduces symptoms of depression, especially among people with secondary depression. www.bmj.com
    Depression Mushroom Drug Psychedelic

    Antidepressant use is increasing worldwide, especially in high-income countries. However, roughly 30 percent of people taking the drugs are resistant to their effects. A recent systematic review and meta-analysis found that people with depressive symptoms who took psilocybin were two times more likely to respond to treatment than those not taking the drug.

    Researchers analyzed the findings of randomized clinical trials that evaluated the effects of psilocybin therapy on depressive symptoms. They included nine studies involving 436 patients in their analysis.

    They found that participants taking psilocybin were two times more likely to respond to treatment than those not taking the drug, especially among those with secondary depression, which can arise due to another medical or psychological issue. Participants experienced few adverse effects, and most were mild and transient. Interestingly, those who had used psychedelics before experienced greater symptom relief, possibly due to “expectancy bias” – a phenomenon where a person’s previous experience makes them expect positive results.

    These findings suggest that psilocybin exerts potent antidepressant effects. Although the treatment response was high, the review’s authors graded the quality of the evidence as “low” due to heterogeneity among the studies, including dose and concomitant psychotherapy.

    Psilocybin is a psychedelic compound present in mushrooms. Learn more about the effects of psilocybin and other psychedelic drugs in this episode featuring Dr. Roland Griffiths.

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  • Physical activity promotes better sleep – reducing stress and improving mood. medicalxpress.com
    Exercise Sleep Depression Wearable Technology

    Physical activity and sleep are essential for human health, and some evidence suggests they work synergistically to promote mental and physical wellness. A recent study found that physical activity improves aspects of sleep, reducing stress levels and improving mood.

    Researchers used wearable sensors and smartphone tracking to monitor heart rates, sleep, activity levels, and mood in 82 healthy adults over six months. They found that people who engaged in low-, moderate-, or vigorous-intensity exercise tended to have more NREM (deep, slow-wave) sleep and less REM (dream) sleep than non-exercisers. They also tended to enter REM sleep sooner. These changes in sleep patterns correlated with better mood, higher energy levels, less stress, and an enhanced perception of having restful sleep.

    These findings support a growing body of evidence suggesting that physical activity and sleep are intrinsically linked. They also highlight the emerging role of wearable technology as a valuable tool in sleep research.

    Wearable sensors and smartphones allow people to monitor their health, fitness, activity, sleep, or mood. Often simply called “wearables,” these devices can transmit information to a physician, researcher, or user in real time, facilitating data collection and allowing the wearer to actively participate in tracking and maintaining their health. Learn more about wearables in this episode featuring Dr. Michael Snyder.

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  • Intense exercise is comparable to psychotherapy and drug treatments for depression, study finds. www.ncbi.nlm.nih.gov
    Exercise Depression Anxiety

    Exercise has profound effects on the brain, stimulating the release of neurotransmitters that enhance mood and cognitive functions. Evidence suggests that regular physical activity can promote long-term improvements in mental health, reducing symptoms of depression and anxiety and fostering a sense of well-being. A recent review and meta-analysis found that exercise, especially intense exercise, is comparable to psychotherapy and drug treatments for depression.

    Researchers analyzed the findings of 218 studies comparing the effects of exercise versus standard treatments or placebos on depression. The various trials included more than 14,000 participants and incorporated different exercise modalities.

    The researchers found that physical activities such as walking, jogging, yoga, strength training, mixed aerobic exercises, and tai chi or qigong moderately reduced depression symptoms compared to standard treatments or placebos. Specifically, walking or jogging markedly reduced depression symptoms, with yoga and strength training also demonstrating notable benefits. Mixed aerobic exercises and tai chi or qigong were also beneficial but to a lesser extent. Notably, exercise intensity was directly linked to the magnitude of depression symptom reduction.

    These findings suggest that exercise is comparable to psychotherapy and drug treatments for depression. However, only one of the studies included in the analysis met the highest standards for quality, creating uncertainty regarding the effectiveness of each exercise type. Sauna use, which mimics many of the physiological effects of exercise, improves mood, too. Learn more in this clip featuring Dr. Rhonda Patrick.

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  • Altered serotonin levels in early life impair the development of the brain's prefrontal cortex – essential for higher cognitive functions. news.cuanschutz.edu
    Brain Depression Serotonin Mental Health Development

    Serotonin is crucial for early brain development, influencing how brain cells communicate and form networks. The prefrontal cortex, a brain region vital for complex cognitive tasks, such as decision-making and social interactions, is heavily influenced by serotonin levels during development. A recent study demonstrates that alterations in serotonin levels during early life impair prefrontal cortex development, driving changes in the density and function of dendritic spines, the tiny structures on neurons essential for brain communication.

    Researchers employed advanced imaging techniques to observe how dendritic spines develop and change in young mice. They also manipulated serotonin levels using genetic tools and monitored the resulting changes in spine density and synaptic function, providing insights into how serotonin shapes neural connectivity during critical developmental periods.

    They found that modifying serotonin levels during development induced notable alterations in the structure and functionality of dendritic spines in the prefrontal cortex. These changes were closely associated with the activity of specific serotonin receptors, which are vital for the growth and adaptability of neuronal connections. Furthermore, exposure to fluoxetine (commonly known as Prozac) during early life had similar effects on dendritic spine development, implicating common antidepressants in the complex interplay of serotonin signaling and brain maturation.

    These findings highlight the pivotal role of serotonin receptors in modulating the growth and plasticity of dendritic spines, underscoring their importance in the serotonin-driven development of the prefrontal cortex. Learn how vitamin D and omega-3 fatty acids influence serotonin levels and brain development in this open-access article coauthored by Dr. Rhonda Patrick.

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  • Cold exposure boosts mood and enhances brain connectivity. www.mdpi.com
    Brain Inflammation Depression Cold Stress Norepinephrine

    Cold exposure has long been used to reduce muscle soreness and promote muscle recovery after physical activity. However, evidence indicates that regular cold exposure also improves glucose and lipid metabolism, decreases inflammation, enhances immune function, and improves cognitive performance. Now, findings from a recent study suggest that cold exposure improves mood and increases connectivity between brain networks.

    The study involved 33 men and women who were unaccustomed to regular cold exposure. The participants underwent functional magnetic resonance imaging (fMRI) to assess their brain network connectivity before and after soaking in a cold water (20°C, 68°F) bath. They also reported on their mood before and after the intervention.

    The participants reported feeling more active, alert, attentive, proud, and inspired after the cold exposure. The fMRIs revealed that the participants' positive moods correlated with increased connectivity in the default mode, frontoparietal, salience, and visual lateral networks, regions of the brain that contribute to self-reflection, attention, emotion regulation, and visual processing.

    The findings from this small study suggest that short-term cold exposure improves mood by enhancing brain connectivity in regions associated with mood. These benefits may arise from the effects of norepinephrine, a neurotransmitter involved in vigilance, focus, attention, and mood. Norepinephrine release is one of the most consistent and profound physiological responses to cold exposure. Learn more about cold exposure and the mechanisms that drive its effects in our comprehensive overview article.

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  • People who cycle to work are less likely to require mental health medications, study finds. academic.oup.com
    Exercise Depression Mental Health Anxiety Mortality

    Regular physical activity can have profound effects on mental health by reducing depression and anxiety. Evidence suggests that cycling to work reduces the risk of premature death from all causes, including cardiovascular disease and cancer. A recent study found that people who cycle to work are also less likely to require mental health medications.

    The study, which took place in Scotland, involved more than 378,000 adult participants living in Edinburgh, Glasgow, and the surrounding areas. Researchers collected data regarding whether the participants cycled to work and if they required a prescription for mental health (anti-anxiety or antidepressant) medications.

    They found that very few commuters cycled to work, with just 4.8 percent of commuters in Edinburgh and 1.85 percent in Glasgow cycling. However, those who did cycle were less likely to have received a prescription for mental health medications than non-cyclists. This difference translated to a 15 percent reduction in mental health prescriptions over five years. Interestingly, men were more likely to cycle and less likely to take mental health medication than women.

    These findings suggest that cycling to work improves mental health and supports public health efforts that encourage commuters who travel shorter distances to consider cycling. Watch this episode in which Dr. Rhonda Patrick talks about her love of cycling for its powerful mood-enhancing effects and describes the compelling science suggesting exercise is a powerful tool for preventing or managing the symptoms of depression and mental illness.

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  • Meta-analysis: Psilocybin therapy yields a threefold likelihood of remission of depression symptoms. www.sciencedirect.com
    Depression Drug Psychedelic

    Nearly 25 million adults living in the United States take antidepressant medications. Unfortunately, 10 to 30 percent of those taking antidepressants are resistant to the drugs' effects. A recent systematic review and meta-analysis found that patients with depression who took psilocybin were more than three times more likely to experience remission than those who didn’t.

    Researchers evaluated the findings of randomized clinical trials and open-label trials that evaluated depression symptoms among patients diagnosed with life-threatening illnesses or major depressive disorder after receiving psilocybin therapy. They included nine studies involving nearly 600 patients in their final analysis.

    They found that participants taking psilocybin were more than twice as likely to have a positive response to therapy than those not taking the drug. They were also more than three times more likely to experience symptom remission.

    These findings suggest that psilocybin exerts potent antidepressant effects when used with psychotherapy. Several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating the symptoms of depression, including exercise, dietary modification, meditation, sauna use, and light therapy. Learn more about these approaches in our overview article on depression.

    Psilocybin is a psychedelic compound present in mushrooms. Learn more about the effects of psilocybin and other psychedelic drugs in this episode featuring Dr. Roland Griffiths.

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  • Psychedelic drugs show potential in easing PTSD and TBI symptoms in military veterans. www.sciencedaily.com
    Brain Depression Anxiety Psychedelic TBI

    Military veterans, especially those engaging in special operations, are at greater risk for developing post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). A recent study found that psychedelic drugs reduce the symptoms associated with PTSD and TBI and improve cognition in special operations veterans.

    The study involved 86 male special operations veterans who had reported experiencing various mental and physical health disorders, including memory/concentration problems, TBI, depression, anxiety, PTSD, sleep problems, anger/rage, and fatigue. Each participant received a single oral dose of ibogaine hydrochloride. On a separate occasion, they received at least three incrementally increasing amounts (totaling 50 milligrams) of 5-MeO-DMT. Before and after each treatment session, they documented their emotional well-being and any other symptoms they experienced.

    The participants reported marked improvements in their PTSD, depression, anxiety, insomnia, and anger symptoms, along with increased life satisfaction, even at six months post-treatment. In addition, their psychological flexibility and cognitive functioning increased, while post-concussion symptoms notably decreased, remaining improved at all follow-ups.

    Participants reported positive changes in attitudes, behaviors, and relationships, and many considered the experience highly meaningful, spiritually significant, and psychologically insightful.

    Ibogaine hydrochloride is a psychedelic drug found in the bark of the Tabernanthe iboga, a shrub native to Central and West Africa. It elicits prolonged effects (beginning 30 minutes to three hours after intake and peaking between 18 and 36 hours), often described as a “waking dream.”

    5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a psychedelic drug obtained from various plants and the glands of the _ Incilius alvarius_ toad. It is a fast-acting, short-duration psychoactive, inducing feelings of awe, visual and auditory hallucinations, and other sensations common with classic psychedelics.

    These findings suggest that psychedelic drugs improve symptoms associated with PTSD and TBI in military special operations veterans. These improvements were still evident at the six-month follow-up when the study ended. It is possible the effects endured even longer. Learn more about the effects of psilocybin and other psychedelic drugs in this episode featuring Dr. Roland Griffiths.

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  • Physical activity reduces depression symptoms by 43 percent, study finds. www.healio.com
    Exercise Depression Anxiety

    Mental health disorders are rising, affecting more than 970 million people worldwide. While lifestyle behaviors can be beneficial in treating these disorders, drugs are often the primary treatment choice. A recent review found that physical activity reduced symptoms of depression by as much as 43 percent.

    Researchers conducted an umbrella review – an analysis that consolidates findings from multiple systematic reviews, providing a comprehensive overview of the existing evidence. Their analysis included 97 reviews, encompassing 1039 randomized controlled trials (128,119 participants) investigating the effects of physical activity on depression, anxiety, or psychological distress.

    They found that various forms of physical activity, including walking, resistance training, Pilates, yoga, and others, reduced symptoms of depression by 43 percent and anxiety by 42 percent, eliciting faster effects than medication. They observed the most pronounced effects in people with depression, pregnant and postpartum women, healthy people, and those with HIV or kidney disease. For people with depression and anxiety, higher-intensity exercise involving bursts of short and mid-duration activities proved more effective than longer-duration exercises.

    These findings demonstrate that physical activity has marked, beneficial effects on mood and may be an effective intervention for many people. The mechanisms that drive these effects likely include increased expression of neurotrophic factors, increased availability of serotonin and norepinephrine, regulation of the hypothalamic-pituitary-adrenal axis, and reduced systemic inflammation. Learn more about some of these mechanisms in this short video featuring Dr. Rhonda Patrick.

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  • Immune cell depletion promotes depression-like behavior, suggesting a role for regulatory T cells in mood stabilization. neurosciencenews.com
    Depression Immune System Anxiety

    Regulatory T-cells, or Tregs, are white blood cells that modulate the body’s immune response. A growing body of evidence points to the role of immune activation in mood disorders, such as anxiety and depression. A new study in mice shows that Foxp3, a transcription factor, influences Treg expression and activity, ultimately influencing mood.

    Researchers depleted the Foxp3-expressing cells in mice and assessed the animals' behavior. They found that Foxp3 depletion caused temporary anxiety and depression-like behaviors due to the activation of inflammasomes, multi-protein complexes that drive the body’s inflammatory response.

    Then, the researchers restored Foxp3-expressing cells in the mice and found that the anxiety and depression-like behaviors improved. They also noted changes in the innate immune system, including increased activity of caspase-1 (a protein that initiates the immune response) and release of interleukin-1β (a pro-inflammatory cytokine) in the brain.

    These findings suggest that Foxp3 plays a causal role in regulating the immune response, which, in turn, can affect the brain’s innate immune system. They also highlight potential mechanisms that may contribute to anxiety and depression. However, this research was conducted in mice, and extrapolating these findings to humans requires further investigation. Learn about some of the underlying mechanisms that drive depression in this short video.

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  • Microglial dormancy in depression challenges conventional understanding centered on inflammation, but highlights the immune cell's crucial role in neu medicalxpress.com
    Brain Inflammation Depression Immune System

    Chronic inflammation is a dominant feature in people who have depression, suggesting that an overactive immune response drives the disease’s symptoms. But a new study demonstrates something counterintuitive in spite of that: Immune cells in the brain called microglia are less active in people with depression, impairing their ability to clear damaged neuronal connections, undermining neurotrophic support, and driving the disease.

    Researchers studied gene expression in the microglia of brain tissues collected during autopsies of 13 people with depression and 10 healthy people. They also examined gene expression of neuronal factors that regulate microglial function.

    They found that the expression of genes in the microglia of people with depression was markedly lower than that of healthy people, especially genes involved in immune responses and phagocytosis (which facilitates the clearance of damaged cells). In addition, the expression of factors involved in immune suppression (CD200 and CD47) was higher.

    These findings suggest that people with depression have a distinct disease-associated microglia gene expression profile that impairs microglia activity. Microglia play critical roles in the development, homeostasis, and diseases of the central nervous system and contribute to neuronal plasticity in the healthy brain. Microglial changes are common features of many neuropsychiatric disorders, including schizophrenia, autism spectrum disorder, and bipolar disorder. Learn more about microglia suppression in depression in this clip featuring Dr. Charles Raison.

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  • Higher protein intake may bolster mood in teens. www.psypost.org
    Diet Depression Development Protein

    According to a new study in teens, higher dietary protein intake improves mood. Adolescent athletes who ate more protein in their diets experienced fewer symptoms of depression.

    The study involved 97 adolescent athletes who reported their depressive symptoms before and after a span of 10 months. About three months into the study period, they completed a three-day diary of their typical dietary intake.

    The food diaries revealed that, in general, the teens ate fewer healthy fats and carbohydrates than recommended, but more sugar than recommended. Their dietary protein intake met recommendations but was typically lower among females than males. Teens that ate higher amounts of protein were less likely to report depressive symptoms than those with lower intake.

    Dietary protein is essential for human health. It provides the building blocks for many biological components, including neurotransmitters in the brain, which play crucial roles in mood, sleep, appetite, and other physiological processes. Although this study did not assess the teens' athletic performance, it’s important to note that protein supports muscle growth and maintenance, ultimately influencing aspects of performance. Learn more about the importance of dietary protein in this episode featuring Dr. Philip Stuart.

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  • Running may be as effective as traditional antidepressant therapies for reducing symptoms of depression. www.sciencedirect.com
    Exercise Brain Depression

    Running may be as effective as traditional antidepressant therapies for reducing symptoms of depression.

    A new study found that running was as effective as traditional antidepressant drugs at reducing symptoms of depression. In addition, people who ran had better physical health than those who did not.

    The study involved 141 people with depression. Participants chose which 16-week therapy intervention they preferred: running at least twice a week with a group (96 participants) or taking traditional antidepressant medication (45 participants). They underwent mental and physical health assessments before and after the interventions.

    The two therapies were comparable in terms of reducing depressive symptoms. However, running therapy improved many aspects of the participants' health, including body weight, waist size, blood pressure, heart rate, and heart rate variability.

    Nearly 25 million adults living in the United States take some form of antidepressant medication. Most antidepressants work by altering the brain’s chemistry to affect mood. Side effects of the drugs include nausea, weight gain, decreased libido, and anxiety, among others. Evidence suggests that antidepressants are only about 20 to 30 percent more effective at reducing symptoms of depression than placebo treatments.

    Exercise boosts the production of molecules that enhance mood and promote mental health. Learn more about the mental health effects of exercise in this video featuring Dr. Rhonda Patrick.

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  • Just two hours of air pollution exposure interferes with regular brain activity. www.sciencedaily.com
    Depression Pollution Blood-Brain Barrier

    Even short-term exposure to air pollution affects brain function, a new study shows. People exposed to diesel exhaust for just two hours had reduced connectivity in areas of the brain associated with attention and focus.

    Researchers exposed 25 healthy adults to diesel exhaust and filtered air for two hours, with a two-week break between each exposure. Before and after the exposures, the researchers measured activity in a region of the participants' brains called the default mode network.

    They found that compared to pre-exposure, participants had reduced connectivity throughout the default mode network of their brains after brief exposure to diesel exhaust. There were no changes in connectivity following exposure to filtered air.

    The default mode network is a collection of interconnected neural structures involved in attention and focus. Disturbances in default mode network connectivity are associated with poor working memory, reduced performance, and work-related productivity losses.

    Sulforaphane, a bioactive compound derived from broccoli – and particularly abundant in broccoli sprouts – promotes urinary excretion of some components of air pollution. Learn more in the clip featuring Dr. Jed Fahey.

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  • Breathing exercises reduce stress and improve mental health. www.news-medical.net
    Depression Stress Meditation Mental Health Anxiety

    Breathwork improves mental health, a new study shows. People who practiced breathwork reported less anxiety, depression, and mental stress, regardless of how frequently they engaged in the practice.

    Researchers reviewed the findings of 12 randomized controlled trials that investigated the effects of breathwork on stress. The breathwork techniques were presented in person, remotely, or via both.

    They found that slow-breathing exercises improved participants' mental health, regardless of how the techniques were presented. Participants who practiced breathwork reported having less anxiety, depression, and mental stress, compared to those who did not practice breathwork. Surprisingly, the researchers didn’t identify a dose-response effect with breathwork, aligning with other findings in which just a single breathwork session reduced anxiety.

    Breathwork is an umbrella term that refers to various breathing exercises and techniques. Evidence suggests that breathwork improves heart rate variability and promotes resilience to stress. People often engage in breathwork as part of general relaxation practices, yoga, or meditation. Learn more about the benefits of meditation in this audio episode featuring Dr. Rhonda Patrick.

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  • Perimenopausal estradiol fluctuations may increase women's sensitivity to social rejection and vulnerability to developing depressive symptoms. (2015) www.sciencedaily.com
    Hormones Depression Stress Mental Health Estrogen

    From the article:

    In addition, the menopausal transition and early postmenopausal period are times of particularly increased vulnerability to depression for women, with rates of MDD [major depressive disorder] and clinical elevations in depressive symptoms doubling or even tripling compared to premenopausal and late postmenopausal rates. A substantial proportion of women–between 26% and 33%–will develop clinically significant depressive symptoms within the context of perimenopausal hormonal flux.

    The common physiological change occurring during the menopausal transition is extreme variability in estradiol concentrations, thus prompting the 12-month placebo-controlled randomized trial evaluating the mood and cardiovascular benefits of transdermal estradiol in perimenopausal women. The findings from the placebo group found that, in general, estradiol variability led to the development of depressive symptoms, as well as greater anger/irritability and feelings of rejection. More specifically, the findings suggest that perimenopausal estradiol fluctuation may increase women’s sensitivity to social rejection, and when this sensitivity is combined with psycho-social stressors such as divorce or bereavement, women are particularly vulnerable to developing clinically significant depressive symptoms. Of note, however, is that the effect of estradiol variability on mood is not the same in all women and, if a severe life stress did not occur, estradiol variability did not lead to depression. Very severe life stresses were defined and included divorce or separation, serious illness of a close relative or friend, significant current financial issues, physical or sexual abuse or assault, significant arrest of self or loved one.

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  • Estrogen protected rats against heart attack-related depression by preventing the production of inflammation-causing chemicals in the brain. (2018) www.sciencedaily.com
    Hormones Heart Disease Depression Estrogen

    From the article:

    Adult female rats without ovaries – mimicking menopause – were compared to adult males and adult females with ovaries. Half of the “menopausal” rats received estrogen supplements while the other half did not. Sex-matched rats without heart failure served as controls. The animals were given several standardized tests to assess depression-like behavior, learning, memory and the ability to experience pleasure. The researchers also took blood samples to measure inflammation levels in the brain (neuroinflammation).

    The male rats, but not the female rats, with heart failure showed signs of depression and brain inflammation compared to their controls. In contrast, the menopausal females displayed higher rates of depression-like behavior than all of the males studied. However, the group receiving estrogen showed no depression – their levels were on par with the control females with ovaries – and no increase in inflammation in brain areas involved in mood and pleasure.

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  • Quality of life in older hypogonadal men may be positively influenced by testosterone substitution. (2020) onlinelibrary.wiley.com
    Hormones Depression Behavior Mental Health Anxiety Genetics Testosterone

    From the publication:

    Testosterone plays a pivotal role in maintaining balance within the multi-dimensional psychological network of mood, behaviour, self-perception and perceived quality of life in men of any age. Apart from classical forms of hypogonadism, low testosterone concentrations can also be seen in older men, described as an age- and comorbidity-driven functional hypogonadism and might relate to depressive symptoms exhibiting a wide array of clinical pictures ranging from dysthymia and fatigue over inertia, listlessness to hopelessness and suicidal thoughts. Also, various traits of anxiety, from unfocussed fear to phobic anxiousness and open panic syndromes, are influenced by testosterone. Correspondingly, anxiolysis is likely to be modulated by testosterone via stress resilience, threat vigilance and reward processing. The steroid modulates pro-active and re-active dimensions of aggression, which has to be seen within the context of gaining or maintaining status. This may also include other strategies impacting the social position: heroic or parochial altruism and non-aggressive paths of assertiveness, such as posture and social vigilance. Independent rather than relationship-associated self-construal and self-esteem influence risk-taking traits under the modulation of testosterone. In addition, the genetic setting of the androgen receptor modulates the role of testosterone in aspects regarding mood and personality. Dimensions of sexuality are rather important in this context, but are not target of this article and covered in another part of this special edition. Overall, the quality of life in older hypogonadal men can be positively influenced by testosterone substitution, as has been demonstrated in large placebo-controlled trials.

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  • Meta-analysis suggests association between testosterone treatment and alleviation of depressive symptoms in men. (2019) jamanetwork.com
    Hormones Depression Mental Health Testosterone

    From the publication:

    To our knowledge, the present meta-analysis is the largest examination to date of the association of testosterone treatment with depressive symptoms in men, including 27 RCTs comprising 1890 men. Replicating and extending previous work, we show evidence for a moderate antidepressant association of testosterone treatment compared with placebo, identifying an effect size of the overall analysis of Hedges g of 0.21.

    […]

    Irrespective of any bias, analysis of potential moderators revealed that dose was a likely moderator, indicating robust effects for dosages higher than 500 mg/wk (Figure 3B). Previous studies failed to detect testosterone dose-response relationships for mood, including for depressive symptoms.

    […]

    Remarkably, initial testosterone status was not a moderator of the effect of testosterone treatment on depressive symptoms. This result contradicts a previously published study showing up to a 3-fold increased incidence of MDD in hypogonadal men.

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  • Antidepressants can affect testosterone and estrogen levels. (2021) www.sciencedirect.com
    Hormones Depression Drug Testosterone Estrogen

    From the publication:

    Firstly, according to the reviewed data from preclinical studies, SSRIs affect to a greater extent, both testosterone and estrogen serum levels compared to the rest of drug classes (Tables 1 and 3). In particular, more than 50% of the reviewed publications report changes in testosterone and estrogen levels after SSRI administration. The same conclusion cannot be drawn from the comparatively fewer studies that investigated other classes of monoaminergic antidepressants. Secondly, data indicated differences between acute and sub-chronic or chronic drug administration on testosterone and estrogen levels. On the one hand, acute antidepressant treatment either decreases or does not affect testosterone and estrogen levels. On the other hand, data from sub-chronic and chronic antidepressant treatment are conflicted, probably due to variable treatment duration and differences in the time and method of sampling. Furthermore, from our reviewed data it appears that testosterone levels are more frequently affected by antidepressants in comparison to estrogen. More specifically, the majority of studies found no changes in estrogen levels following drug administration, whereas the rest of the studies reported either increased or decreased levels of testosterone in both males and females (Tables 1 and 3). Unfortunately, inconsistencies in methods, i.e., inclusion of both sexes, doses, age, duration, and strain, as well as the technical difficulties in measuring low and variable estrogen levels account for the conflicting data and impede any firm conclusions.

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  • High-dose testosterone treatment increased serotonin transporter binding in transgender people. (2015) www.sciencedaily.com
    Hormones Depression Mental Health Neurotransmitter Testosterone

    From the article:

    As they grow older and as their sex hormone output falls, men suffer more commonly from depression and some studies have already demonstrated a positive effect of testosterone supplementation on the moods of the test subjects. Now, the study led by Rupert Lanzenberger from the University Department of Psychiatry and Psychotherapy has demonstrated for the first time worldwide that testosterone increases the number of serotonin transporters (proteins) in the human brain. These proteins regulate the concentration of serotonin and are also the target for antidepressants.

    Serotonin transporters increased after just four weeks of hormone therapy

    […]

    “The study has shown that testosterone increases the potential binding sites for commonly prescribed antidepressants such as SSRIs in the brain and therefore provides major insights into how sex hormones affect the human brain and gender differences in psychiatric illnesses,” says Siegfried Kasper, Head of the University Department of Psychiatry and Psychotherapy at the MedUni Vienna.

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  • Men with borderline testosterone levels may be at risk for depression. (2015) www.sciencedaily.com
    Hormones Depression Mental Health Testosterone

    From the article:

    The number of men having their testosterone levels checked has increased dramatically. Studies of the possible association between depression and serum testosterone show inconsistent results, and few studies have been published about adult men referred for the management of borderline testosterone.

    Dr. Irwig and his colleagues studied 200 adult men between 20 and 77 years of age whose testosterone levels were borderline (between 200 and 350 nanograms per deciliter).

    […]

    Using a score of 10 or higher on the PHQ-9 [Patient Health Questionnaire 9], 56% of the study participants had significant depressive symptoms, known diagnosis of depression and/or use of an antidepressant. Their rates of depressive symptoms were markedly higher than the 15 to 22% in an ethnically diverse sample of primary care patients and the 5.6% among overweight and obese US adults.

    The population also had a high prevalence of overweight (39%), obesity (40%) and physical inactivity; other than walking, 51% of the men did not engage in regular exercise. The most common symptoms reported were erectile dysfunction (78%), low libido (69%) and low energy (52%).

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  • Low free testosterone levels may be associated with up to a threefold risk of depression in older men. (2008) www.sciencedaily.com
    Depression

    From the article:

    Osvaldo P. Almeida, M.D., Ph.D., F.R.A.N.Z.C.P., of the University of Western Australia, Perth, and colleagues studied 3,987 men age 71 to 89 years.

    […]

    A total of 203 of the participants (5.1 percent) met criteria for depression; these men had significantly lower total and free testosterone levels then men who were not depressed. After controlling for other factors – such as education level, body mass index and cognitive scores – men in the lowest quintile (20 percent) of free testosterone concentration had three times the odds of having depression compared to men in the highest quintile.

    The mechanism by which low hormone levels might affect depression risk has not been identified, but might involve changes in the levels of neurotransmitters or hormones in the brain, the authors note.

    “A randomized controlled trial is required to determine whether reducing prolonged exposure to low free testosterone is associated with a reduction in the prevalence of depression in elderly men,” the authors write.

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  • Testosterone may mediate antidepressant effects via ERK2 signaling, rat study suggests. (2012) www.sciencedaily.com
    Hormones Depression Mental Health Testosterone Neurogenesis

    From the article:

    Compared to men, women are twice as likely to suffer from an affective disorder like depression. Men with hypogonadism, a condition where the body produces no or low testosterone, also suffer increased levels of depression and anxiety. Testosterone replacement therapy has been shown to effectively improve mood.

    Although it may seem that much is already known, it is of vital importance to fully characterize how and where these effects are occurring so that scientists can better target the development of future antidepressant therapies.

    To advance this goal, the scientists performed multiple experiments in neutered adult male rats. The rats developed depressive-like behaviors that were reversed with testosterone replacement.

    They also “identified a molecular pathway called MAPK/ERK2 (mitogen activated protein kinase/ extracellular regulated kinase 2) in the hippocampus that plays a major role in mediating the protective effects of testosterone,” said Kabbaj.

    This suggests that the proper functioning of ERK2 is necessary before the antidepressant effects of testosterone can occur. It also suggests that this pathway may be a promising target for antidepressant therapies.

    Kabbaj added, “Interestingly, the beneficial effects of testosterone were not associated with changes in neurogenesis (generation of new neurons) in the hippocampus as it is the case with other classical antidepressants like imipramine (Tofranil) and fluoxetine (Prozac).”

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  • Aerobic exercise reduces symptoms of anxiety. bmchealthservres.biomedcentral.com
    Exercise Depression Anxiety Blood-Brain Barrier Lactate

    Aerobic exercise – especially high-intensity exercise – reduces symptoms of anxiety, an analysis of 15 studies shows. These anti-anxiety effects endured for several months after cessation of the exercise.

    Reviewers analyzed data from 15 studies that investigated the effects of low- or high-intensity exercise on anxiety symptoms. All the participants in the studies had some degree of anxiety, with their conditions falling on a spectrum that included anxiety disorders, raised anxiety levels, and raised anxiety sensitivity – a condition in which a person feels anxious about the physical symptoms that often accompany anxiety. People on waiting lists for anxiety treatment who did not exercise served as comparisons.

    They found that participants who engaged in both low- and high-intensity aerobic exercise experienced greater improvements in their anxiety than non-exercising people on treatment waiting lists. High-intensity exercise reduced anxiety symptoms more effectively than low-intensity exercise. The various interventions lasted between 10 weeks and six months, with participants exercising three times a week, on average.

    Multiple mechanisms may be responsible for the anti-anxiety effects of exercise. For example, high-intensity exercise promotes the production of lactate, a byproduct of glucose metabolism that participates in the production of neurotransmitters, such as norepinephrine and serotonin. Low norepinephrine and serotonin levels can drive anxiety and the inability to handle stressful situations. Learn more about lactate and its effects on the brain in this episode featuring Dr. George Brooks.

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  • A drop in testosterone levels over time is more likely to result from a man’s behavioral and health changes than by aging, study suggests. (2012) www.sciencedaily.com
    Obesity Aging Hormones Depression Mental Health Sex Testosterone

    From the article:

    On average, testosterone levels did not decline significantly over five years; rather, they decreased less than 1 percent each year, the authors reported. However, when the investigators analyzed the data by subgroups, they found that certain factors were linked to lower testosterone levels at five years than at the beginning of the study.

    “Men who had declines in testosterone were more likely to be those who became obese, had stopped smoking or were depressed at either clinic visit,” Wittert said. “While stopping smoking may be a cause of a slight decrease in testosterone, the benefit of quitting smoking is huge.”

    […]

    Unmarried men in the study had greater testosterone reductions than did married men. Wittert attributed this finding to past research showing that married men tend to be healthier and happier than unmarried men. “Also, regular sexual activity tends to increase testosterone,” he explained.

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  • Testosterone may need to be converted to estrogen in the brain to show anxiety- and depression-inhibiting effects, mouse study suggests. (2015) www.sciencedaily.com
    Hormones Depression Mental Health Anxiety Testosterone Estrogen

    From the article:

    He already knew that testosterone had a protective effect on males, just as estrogen and progesterone do on females. He also knew that most testosterone was converted into estrogen in the brain. What he didn’t know was that those anxiety- and depression-inhibiting effects couldn’t be produced unless the testosterone was first converted to estrogen.

    “There is an enzyme in the brain that ‘mediates’ the conversion of testosterone into estrogen,” Kabbaj said. “We inhibited that enzyme in a specific brain area implicated in the regulation of mood. And when you do that, you lose the antidepressant effect of testosterone. So the conversion is very important.”

    His lab targeted the hippocampus area of the brain, where testosterone acts through what’s known as the MAPK pathway to induce its antidepressant and anti-anxiety effects.

    “But we have to be careful about that pathway,” Kabbaj said, “because it’s also implicated in cellular growth and cancer. Therefore, we’re looking for other pathways that don’t have these effects. It’s complicated. Nothing is ever simple, but we’ll get there.”

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  • In a study of men with low testosterone, 56% of study participants suffered from depression or showed depressive symptoms. (2015) www.sciencedaily.com
    Obesity Sleep Hormones Depression Mental Health Sex Testosterone

    From the article:

    The research, slated to publish online on July 1 in the Journal of Sexual Medicine, involved 200 adult men, aged 20-77, with a mean age of 48 years old, who were referred for borderline total testosterone levels between 200 and 350 ng/dL. Information gathered included demographics, medical histories, medication use, signs and symptoms of hypogonadism, and assessments of depressive symptoms and/or a known diagnosis of depression or use of an antidepressant.

    Depression and/or depressive symptoms were present in 56 percent of the subjects. Furthermore, one quarter of the men in the study were taking antidepressants and that the men had high rates of obesity and low rates of physical activity. The most common symptoms were erectile dysfunction, decreased libido, fewer morning erections, low energy, and sleep disturbances.

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  • Low testosterone levels may be associated with chronic disease, even in men 40 years of age and younger. (2018) www.sciencedaily.com
    Hormones Diabetes Cholesterol Depression Testosterone Triglycerides Blood Pressure Arthritis Cardiovascular

    From the aricle:

    Peterson and team then examined prevalence of nine chronic conditions, including type 2 diabetes, arthritis, cardiovascular disease, stroke, pulmonary disease, high triglycerides, hypercholesterolemia, hypertension and clinical depression.

    The researchers studied the prevalence of multimorbidity, or when two or more of the chronic conditions were present, among three age groups (young, middle-aged and older men) with and without testosterone deficiency. They found that low total testosterone [<300 ng/dL] was associated with multimorbidity in all age groups – but it was more prevalent among young and older men with testosterone deficiency.

    “We also found a large dose-response relationship between the age-specific low total testosterone and moderate total testosterone levels and multimorbidity, even after adjusting for obesity and muscle strength capacity,” Peterson says. “Which means that men should be concerned about declining total testosterone, even if it has not reached a level to warrant a clinical diagnosis (<300 ng/dL [10.4 nmol/L]).”

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  • Higher omega-6:omega-3 ratios may be associated with progressive increases in TNF-α and interleukin-6 levels as depressive symptoms increase. (2007) www.sciencedaily.com
    Omega-3 Inflammation Depression IL-6 TNF-Alpha

    From the article:

    The study, conducted in OSU’s Institute for Behavioral Medicine Research, focused on a group of 43 middle-aged to elderly men and women, nearly half of which were the caregiver spouses of people with Alzheimer’s or other dementias. By including caregivers who typically report greater stress and more depression than similar ad ults who are not caregiving, the researchers could look at how depression and diet might interact to affect inflammation.

    […]

    The analysis showed that participants who had much more omega-6 – compared to omega-3 – fatty acids, and who also were reporting more symptoms of depression, had much higher levels of IL-6 and TNF-alpha, two cytokines which enhance inflammation.

    “The data suggest that higher depression and a poorer diet in terms of omega-3 can work together to promote inflammation. Other researchers have shown that clinically depressed people – those with more severe depression – often have lower omega-3 levels in their blood, and several studies have shown that supplementing diets with omega-3 improves depression,” Kiecolt-Glaser said, although the reason isn’t clear.

    […]

    “This study has shown that even in people who did not take supplements, maybe just a little bit more omega-3, could help reduce their markers for both stress and depression,” Belury said.

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  • Interleukin-6, CRP and triglycerides are likely shared causal risk factors for depression and coronary heart disease. (2019) www.sciencedaily.com
    Brain Heart Disease Inflammation Depression Triglycerides IL-6 CRP

    From the article:

    Together, these results suggest that the link between heart disease and depression cannot be explained by a common genetic predisposition to the two diseases. Instead, it implies that something about an individual’s environment – such as the risk factors they are exposed to – not only increases their risk of heart disease, but at the same time increases their risk of depression.

    […]

    Of these common biomarkers, they found that triglycerides (a type of fat found in the blood) and the inflammation-related proteins IL-6 and CRP were also risk factors for depression.

    Both IL-6 and CRP are inflammatory markers that are produced in response to damaging stimuli, such as infection, stress or smoking. Studies by Dr Khandaker and others have previously shown that people with elevated levels of IL-6 and CRP in the blood are more prone to develop depression, and that levels of these biomarkers are high in some patients during acute depressive episode. Elevated markers of inflammation are also seen in people with treatment resistant depression. This has raised the prospect that anti-inflammatory drugs might be used to treat some patients with depression. Dr Khandaker is currently involved in a clinical trial to test tocilizumab, an anti-inflammatory drug used for the treatment of rheumatoid arthritis that inhibits IL-6, to see if reducing inflammation leads to improvement in mood and cognitive function in patients with depression.

    While the link between triglycerides and coronary heart disease is well documented, it is not clear why they, too, should contribute to depression. The link is unlikely to be related by obesity, for example, as this study has found no evidence for a causal link between body mass index (BMI) and depression.

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  • Stress-induced chronic inflammation is associated with depression and other diseases. (2015) www.sciencedaily.com
    Exercise Brain Inflammation Depression Stress Meditation Mental Health NSAID IL-6 CRP

    From the article:

    The authors found that in addition to being linked to numerous physical health issues, including cancer and diabetes, systemic inflammation is linked to mental health issues such as depression. Among patients suffering from clinical depression, concentrations of two inflammatory markers, CRP and IL-6, were elevated by up to 50 percent.

    Fagundes said chronic inflammation is most common in individuals who have experienced stress in their lives, including lower socio-economic status or those who experienced abuse or neglect as children. Other contributing factors are a high-fat diet and high body mass index.

    […]

    The study also found that depression caused by chronic inflammation is resistant to traditional therapy methods, but can be treated with activities such as yoga, meditation NSAIDS and exercise.

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  • TNF is associated with reversible depression-like phenotype in hamsters induced by chronic nocturnal dim light exposure. (2012) www.sciencedaily.com
    Brain Depression Circadian Rhythm TNF-Alpha

    From the article:

    While hamsters exposed to light at night for four weeks showed evidence of depressive symptoms, those symptoms essentially disappeared after about two weeks if they returned to normal lighting conditions.

    Even changes in the brain that occurred after hamsters lived with chronic light at night reversed themselves after returning to a more normal light cycle.

    These findings add to the growing evidence that suggest chronic exposure to artificial light at night may play some role in the rising rates of depression in humans during the past 50 years, said Tracy Bedrosian, lead author of the study and doctoral student in neuroscience at Ohio State University.

    “The results we found in hamsters are consistent with what we know about depression in humans,” Bedrosian said.

    […]

    Most importantly, hamsters that lived in dim light showed increased expression of the gene that produces tumor necrosis factor.

    […]

    They found that blocking effects of that protein, called tumor necrosis factor, prevented the development of depressive-like symptoms in hamsters even when they were exposed to light at night.

    […]

    However, hamsters that were returned to a standard light-dark cycle after four weeks of dim light at night saw their TNF levels and even their density of dendritic spines return essentially to normal.

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  • RCT suggests that TNF-alpha antagonism may improve depressive symptoms in patients with high inflammatory biomarkers. (2012) www.sciencedaily.com
    Brain Inflammation Depression TNF-Alpha CRP

    From the article:

    Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, including anti-depressant medications and psychotherapy. This study was designed to see whether blocking inflammation would be a useful treatment for either a wide range of people with difficult-to-treat depression or only those with high levels of inflammation.

    […]

    Study participants all had major depression and were moderately resistant to conventional antidepressant treatment. Each participant was assigned either to infliximab or to a non-active placebo treatment.

    When investigators looked at the results for the group as a whole, no significant differences were found in the improvement of depression symptoms between the drug and placebo groups. However, when the subjects with high inflammation were examined separately, they exhibited a much better response to infliximab [TNF inhibitor] than to placebo.

    Inflammation in this study was measured using a simple blood test that is readily available in most clinics and hospitals and measures C-reactive protein or CRP. The higher the CRP, the higher the inflammation, and the higher the likelihood of responding to the drug.

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  • Eating during the day, rather than at night, improves mood. www.sciencedaily.com
    Depression Circadian Rhythm Time-Restricted Eating

    People who regularly keep late hours – for leisure, shift work, or other reasons, such as caring for a newborn – often have misaligned circadian rhythms, placing them at greater risk for depression and anxiety. Research has shown that daytime eating helps realign those rhythms. Findings from a recent study suggest that eating during the day, rather than at night, reduces the risk of depression and anxiety-related disorders.

    The investigators subjected 19 healthy adults (average age, 26 years) to a unique protocol that altered the participants' light exposure, desynchronizing their normal circadian rhythms and mimicking the effects of shift work. During the desynchronized period, half of the participants ate their meals in both the daytime and nighttime, while the other half ate all their meals in the daytime. The investigators monitored the participants' food intake, sleep duration, and depression- and anxiety-like mood levels.

    They found that among participants who ate during both the day and night, depression-like mood levels increased by 26 percent, and anxiety-like mood levels increased by 16 percent. However, participants who ate all their meals during the day did not experience mood changes. Even though the groups' caloric intake, macronutrient intake, physical activity, sleep duration, and eating window duration (12 hours) were identical, eating during the night worsened their moods. As the participants' eating became more misaligned, their symptoms became more severe.

    These findings suggest that restricting mealtimes to daytime hours can offset the mood-altering effects of misaligned circadian rhythms. Learn more about the effects of time-restricted eating on circadian rhythms in this clip featuring Dr. Satchin Panda.

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  • Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014) www.sciencedaily.com
    Brain Heart Disease Diabetes Depression Mental Health IL-6 CRP

    From the article:

    Now, researchers have carried out the first ever longitudinal study – a study that follows the same cohort of people over a long period of time – to examine the link between these markers [cytokines such as interleukin-6] in childhood and subsequent mental illness.

    A team of scientists led by the University of Cambridge studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children – also known as Children of the 90s – taking blood samples at age 9 and following up at age 18 to see if they had experienced episodes of depression or psychosis. The team divided the individuals into three groups, depending on whether their everyday levels of IL-6 were low, medium or high. They found that those children in the ‘high’ group were nearly two times more likely to have experienced depression or psychosis than those in the ‘low’ group.

    […]

    The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. People with depression and schizophrenia are known to have a much higher risk of developing heart disease and diabetes, and elevated levels of IL-6 have previously been shown to increase the risk of heart disease and type 2 diabetes.

    Professor Peter Jones, Head of the Department of Psychiatry and senior author of the study, says: “Inflammation may be a common mechanism that influences both our physical and mental health. It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.”

    […]

    This potential common mechanism could help explain why physical exercise and diet, classic ways of reducing risk of heart disease, for example, are also thought to improve mood and help depression. The group is now planning additional studies to confirm whether inflammation is a common link between chronic physical and mental illness.

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  • Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010) www.sciencedaily.com
    Brain Depression IL-6

    From the article:

    Activation of the immune system caused mice to learn to run less on wheels in their cages – an activity they normally like. The mice resumed their normal activity when the action of interleukin-6, an immune hormone that carries “sickness” signals to the brain, was blocked.

    “Our findings suggest that blocking the action of interleukin-6 might reduce depression symptoms, like fatigue or loss of interest in pleasurable activities, in people who are depressed and who have elevated levels of interleukin-6,” said Simon Sydserff, PhD, a senior research scientist at BrainCells Inc., who conducted the research while with AstraZeneca Pharmaceuticals.

    Scientists previously observed that some people became depressed due to an immune response to illness or stress. Elevated levels of immune hormones like interleukin-6 have been found in some depressed patients who are otherwise healthy.

    Learn more about depression in our overview article.

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  • Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013) www.sciencedaily.com
    Brain Inflammation Depression IL-6

    Psychosocial stress promotes the release of IL-6, potentially driving the development of depression.

    Psychosocial stress, such as that experienced with divorce, discrimination, trauma, or the death of a child, can have profound effects on the human body. For example, evidence indicates that stress alters the immune system, driving inflammatory processes and impairing antiviral responses. Findings from a 2013 study suggest that psychosocial stress promotes the release of interleukin 6 (IL-6), potentially driving the development of depression.

    IL-6 is a pro-inflammatory cytokine that plays an important role as a mediator of fever and the body’s immune response. It is produced by almost all immune cells and is induced in the context of infection, autoimmunity, or cancer. Many physiological processes are influenced by IL-6, including glucose metabolism, blood cell production, neuroendocrine regulation, and fatigue, among others. IL-6 levels are often elevated in people who have depression.

    The investigators conducted their study using mice that had undergone radiation to destroy their bone marrow, compromising their immune function. Then they transplanted bone marrow from mice that exhibited either high or low levels of IL-6 levels in response to stress into the immune-compromised animals. Then they exposed the animals to a social stressor.

    They found that mice that received transplants from those that exhibited high IL-6 levels in response to stress demonstrated more depression-like behaviors than the mice that received transplants from those that exhibited low IL-6 levels. These findings suggest that IL-6 promotes a pro-inflammatory state that promotes depression-like symptoms in response to psychosocial stress. Identifying therapeutic strategies that inhibit IL-6 may benefit people who are vulnerable to the effects of psychosocial stress.

    Interestingly, hyperthermia, such as that experienced with sauna use or hot baths, has been shown to reduce IL-6 levels. Learn more about the beneficial effects of sauna use in our overview article.

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  • Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021) www.sciencedaily.com
    Brain Inflammation Depression Mental Health IL-6

    Microglia and IL-6 drive the negative mood often associated with inflammation.

    People who have certain neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, or stroke, often exhibit low mood. Evidence suggests that inflammation plays a role in the pathogenesis of these neurological disorders and likely influences mood, as well. Findings from a 2021 study suggest that microglia activation drives the low mood often associated with neurological disorders.

    Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.

    The investigators used chemogenetics, a research technique that uses drugs or other chemicals to modulate neural activity, to stimulate microglia activation in the brains of mice. They noted that levels of interleukin-6 (IL-6, a pro-inflammatory cytokine) and prostaglandins (hormone-like molecules that are involved in inflammation) increased in the animals' brains. In addition, the animals exhibited a low mood. Blocking microglia activity restored the animals' positive mood, however.

    These findings suggest that microglia drive the low mood often associated with inflammation and that IL-6 is a prominent player in this process. Learn more about the role of inflammation and mood in this episode featuring Dr. Charles Raison.

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  • Antidepressant effects of omega-3 EPA may occur in the brain even though brain content is low (it is present in microglia and involved in signaling) www.sciencedirect.com
    Brain Omega-3 Inflammation Depression Immune System Behavior

    From the article:

    It was previously assumed that because EPA is extremely low in the brain it did not cross the blood-brain barrier and any therapeutic effects it exerted would be via the periphery. However, more recent studies have established that EPA does enter the brain, but is rapidly metabolised following entry. While EPA does not accumulate within the brain, it is present in microglia and homeostatic mechanisms may regulate its esterification to phospholipids that serve important roles in cell signaling. Furthermore, a variety of signaling molecules from EPA have been described in the periphery and they have the potential to exert effects within the brain. If EPA is confirmed to be therapeutic in major depression as a result of adequately powered randomized clinical trials, future research on brain EPA metabolism could lead to the discovery of novel targets for treating or preventing major depression.

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  • Effective clinical treatment of depression may require addressing underlying loss of blood-brain barrier integrity www.sciencedaily.com
    Brain Depression Blood-Brain Barrier

    From the article:

    The researchers examined blood-brain barrier cells in depressed stressed mice, resilient stressed mice, and control mice. Their observations show that the epigenetic processes that allow the expression of the claudin-5 gene are more readily activated in resilient mice. They also observed that the resilient mice produce less of one of the proteins that inhibit expression of the claudin-5 gene.

    Conversely, depressed stressed mice express more of an enzyme called HDAC1 that triggers a loss of claudin-5. “When a chemical compound is used to block HDAC1, the depressive mice produce more claudin-5 and their social interactions spontaneously increase,” says Professor Ménard.

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  • APOE4 carriers had a 4.92 higher odds of committing suicide in a high air pollution environment (mexico city) www.sciencedaily.com
    Brain Alzheimer's Depression Genetics Pollution

    Air pollution exposure promotes Alzheimer’s disease-related hallmarks in the brains of children.

    Components present in air pollution – a mixture of chemicals, gases, and particulate matter – can cross biological barriers, including the blood-brain barrier. Evidence suggests that children exposed to air pollution exhibit altered brain structure and metabolic function and demonstrate impaired cognitive performance. A 2018 study identified pathological hallmarks associated with Alzheimer’s disease in the brains of children and young adults living in Mexico City, an area known for its high levels of air pollution.

    The primary pathological hallmarks associated with Alzheimer’s disease are amyloid-beta plaques and tau neurofibrillary tangles. Amyloid-beta is a toxic 42-amino acid peptide that clumps together, forming plaques in the brain. Tau is a protein that, when modified via the chemical process of phosphorylation, can form aggregates called neurofibrillary tangles in the brain. Scientists classify the severity of neurofibrillary tangle formation according to the Braak staging system, which ranks severity on a scale of I to VI, with VI being the most severe.

    The investigators examined autopsy-derived brain tissues from 203 subjects living in Mexico City, ranging in age from 11 months to 40 years, to identify the presence of amyloid-beta plaques and tau neurofibrillary tangles. They calculated the subjects' cumulative burden of particulate matter exposure based on their place of residence and noted the subjects' cause of death. They also conducted genotyping to determine whether the subjects were carriers of APOE4, a genetic variant that increases a person’s risk of developing Alzheimer’s disease.

    They found that 99.5 percent of the subjects' brains exhibited abnormally high levels of amyloid-beta and hyperphosphorylated tau, even as early as 11 months of age. Approximately one-fourth of subjects between the ages of 30 and 40 years exhibited stage III or IV neurofibrillary tangles. Subjects who carried the APOE4 variant were at least 23 times more likely to exhibit stage IV tangles. Interestingly, APOE4 carriers were nearly five times more likely to commit suicide than non-carriers.

    These findings suggest that exposure to air pollution in early life increases a person’s risk for developing Alzheimer’s disease. People who carry the high-risk genetic variant APOE4 are at substantially greater risk and may, additionally, be vulnerable to greater suicide risk. Omega-3 fatty acids help maintain blood-brain barrier integrity and may reduce the risk of Alzheimer’s disease in APOE4 carriers. Learn more in this open-access peer-reviewed article by Dr. Rhonda Patrick.

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  • A mitochondrial link to depression: master regulator of mitochondrial biogenesis PGC-1 alpha protects mice from stress-induced depression www.sciencedaily.com
    Exercise Brain Depression Mitochondria

    From the article:

    It was known that the protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity. In this study researchers used a genetically modified mouse with high levels of PGC-1a1 in skeletal muscle that shows many characteristics of well-trained muscles (even without exercising).

    These mice, and normal control mice, were exposed to a stressful environment, such as loud noises, flashing lights and reversed circadian rhythm at irregular intervals. After five weeks of mild stress, normal mice had developed depressive behaviour, whereas the genetically modified mice (with well-trained muscle characteristics) had no depressive symptoms.

    Eliminating the neurotoxic effects of kynurenine:

    The researchers discovered that mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KAT. KATs convert a substance formed during stress (kynurenine) into kynurenic acid, a substance that is not able to pass from the blood to the brain. The exact function of kynurenine is not known, but high levels of kynurenine can be measured in patients with mental illness.

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  • Pharmaceutical maker reports benefits of psilocybin on severe depression. www.forbes.com
    Depression

    Scientific interest in the therapeutic potential of psilocybin – the active ingredient of “magic mushrooms” (which remain illegal in much of the United States, with some exceptions) has increased in recent years. Now, findings presented in a press release from a pharmaceutical maker indicate the compound might be a promising therapy for treatment-resistant depression – albeit with some serious side effects.

    The findings add to a growing, though uncertain, body of research surrounding psilocybin’s effectiveness. While previous work indicates that it might offer a safe and effective alternative to traditional drug therapies for some mental health disorders, flawed features of study design have cast doubt on their conclusions. These include small sample sizes, failure to compare psilocybin to other drugs or placebos, and difficulties with blinding (shielding participants from information about which drug or dosage they are taking).

    The recent trial addresses several of these issues with a sample size of 233 patients with treatment-resistant depression recruited across ten countries in North America and Europe. It also features the crucial element of double-blinding, a procedure that ensures neither the investigator nor the participant knows which treatment or dose is provided. Participants received one of three psilocybin doses: 25, 10, or 1 milligram (treated as an inactive dose, equivalent to a placebo) The study investigators then assessed participants’ depressive symptoms over time.

    As early as two days after taking the highest dose of psilocybin, participants' depression scores markedly improved, an effect that endured up to six weeks. Twelve weeks after treatment, approximately 24 percent of high-dose recipients maintained an improved mental state compared to 10 percent from the “placebo” group.

    These findings offer evidence that psilocybin might help treat severe depression. Nonetheless, the authors flagged several side-effects of high dosage, ranging from mild symptoms, such as headaches, nausea, and fatigue, to rare, but serious, adverse effects, such as suicidal ideations and self-harm. These severe symptoms affected 11 high-dose recipients, compared to just a single patient from the inactive dose group. The observation suggests potential cause for concern, and the FMF team looks forward to these preliminary results being discussed in greater detail in a peer-reviewed publication.

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  • Exposure to air pollution increases depression risk. apple.news
    Depression Pollution

    Depression is a complex neuropsychiatric disorder that affects millions of people worldwide. Although many factors contribute to a person’s risk for developing depression, such as childhood trauma or stressful life events, genetic predisposition for the condition plays a prominent role. Findings from a recent study suggest that air pollution exerts harmful neuropsychiatric effects, especially among people genetically predisposed to depression.

    Air pollution contains myriad toxic substances, including chemicals, gases, and particulate matter – a mixture of solid particles and liquid droplets that may have neurotoxic properties. Exposure to air pollution promotes oxidative stress and increases the risk of developing many chronic diseases, including cardiovascular disease, cancer, hypertension, and diabetes, markedly shortening people’s lives.

    The new study involved 352 healthy adults living in Beijing, China, a city known for its high levels of air pollution and relatively homogeneous population. The investigators determined each participant’s genetic propensity for developing depression – referred to as a polygenic risk score – and tracked air quality near the participants' homes. Participants completed various mental tasks while undergoing brain scans.

    The scans revealed that people who were exposed to air pollution performed poorly on mental tasks. This effect was more pronounced among those who had a higher polygenic risk score for depression as well as those exposed to the highest levels of air pollution. The findings held true even after considering other factors, such as age, sex, and education, which can influence depression risk.

    These findings suggest that air pollution impairs neurocognitive function, especially among people genetically predisposed to depression. They also underscore public health efforts to ameliorate the harmful effects of pollution. Some evidence indicates that dietary components, such as omega-3 fatty acids and sulforaphane (a bioactive compound derived from broccoli), may negate some of the harmful effects of exposure to air pollution. Watch this clip in which Dr. Jed Fahey describes how sulforaphane provides protection from benzene, a carcinogenic compound present in air pollution.

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  • Whole-body hyperthermia improves aspects of mood. www.tandfonline.com
    Depression Sauna

    A growing body of evidence demonstrates that whole-body hyperthermia improves mood and reduces symptoms of depression. The devices used in many hyperthermia studies have not received FDA approval for investigations conducted in the United States, hindering research progress. Findings from a recent study suggest that a commercially available infrared sauna device induces whole-body hyperthermia and improves aspects of mood.

    Traditional saunas are typically wood-paneled rooms heated by infrared or conventional heaters. However, in recent years, single-person tent-like infrared saunas that spare the head from high temperatures have become popular due to their portability, ease of use, and relatively low cost.

    The study involved 25 physically and mentally healthy males and females (average age, 31 years). Participants completed one whole-body hyperthermia session in a Clearlight Sauna Dome until they achieved a core body temperature of 101.3°F (38.5°C) and maintained that temperature for two consecutive minutes. They remained in the sauna for a 30-minute cool-down period, with the heat turned off. Research staff provided the participants with water and applied cool cloths and ice to their head and neck throughout the sessions. Participants completed questionnaires about their mood and affect before the session and one week later.

    The investigators found that participants reported fewer depression symptoms and less negative affect one week after the sauna session, compared to prior to the session. None of the participants experienced any adverse effects from their session, and most reported only minor complaints related to feeling hot or thirsty.

    These findings indicate that sauna use may reduce symptoms of depression and may be accessible via a widely available commercial sauna device. Learn more about this research in this episode featuring Dr. Ashley Mason.

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  • Methyl donor supplements negate harmful effects of high-sugar diet. apple.news
    Brain Depression Anxiety

    Depression and anxiety are neuropsychiatric diseases characterized by neurological dysfunction and poor mental health. Oxidative stress, which is caused by an imbalance in the concentration of reactive oxygen species and antioxidant compounds, may be one driver of neurological damage in the development of depression and anxiety. Findings of a new report demonstrate the ability of methyl donor supplementation to reduce oxidative stress in the brain and relieve depression and anxiety symptoms in rats eating a high-sugar diet.

    Methyl donors (e.g., choline, betaine, folate, vitamin B12) are nutrients that provide a methyl group (one carbon and three hydrogen molecules) for a series of chemical reactions in the body. Methyl donors interact with the methyl carrier, S-adenosyl-L-methionine (SAM) and methylation enzymes to complete the transfer of a methyl group from the donor to a target protein, lipid, or nucleic acid. Methylation of nucleic acids in DNA and ribonucleic acids in RNA is necessary for epigenetic modifications and gene expression. Good dietary sources of methyl donors include egg yolks and soy foods (high in choline); whole grains (high in betaine); green vegetables (high in folate); and meat, dairy, and fortified products (high in vitamin B12).

    Methyl groups may also have antioxidant properties that protect the body from oxidative damage due to environmental stress, such as a high sugar diet, and emotional stress. Previous research has demonstrated the ability of methyl donor supplementation to reduce the metabolic and neuropsychiatric impairments caused by a high sugar diet in rats.

    The investigators fed 21 female rats a standard chow diet with either tap water (7 rats) or drinking water with 23 percent fructose added (equivalent to twice the sugar concentration of most sodas)(14 rats). After 10 weeks, the investigators gave half of the rats in the fructose group methyl donor supplements (i.e., choline, betaine, folate, and vitamin B12). The rats continued the study for an additional eight weeks. The researchers measured the effects of fructose and methyl donors on metabolism, behavior, and brain health.

    A high-fructose diet caused increased weight gain, fasting glucose and triglycerides, and anxiety and depression behaviors compared to a standard diet. A high-fructose diet also increased oxidative damage and lipid peroxidation in the neurons of the hippocampus, a key brain region damaged by depression and anxiety. After eight weeks of methyl donor supplementation, this hippocampal damage was reversed, reducing depression and anxiety behavior. Methyl donor supplementation also normalized glucose, triglyceride, and cholesterol levels among rats consuming a high-fructose diet.

    These results demonstrate the efficacy of methyl donor supplementation to reduce or reverse the promotion of obesity, metabolic disease, and depression and anxiety on a high-fructose diet in rats.

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  • Co-supplementation with magnesium and vitamin D aids weight loss, improves mood, and reduces systemic inflammation. pubmed.ncbi.nlm.nih.gov
    Vitamin D Obesity Inflammation Depression Magnesium IL-6

    For decades, deficiencies in micronutrients such as magnesium and vitamin D have been linked to conditions such as depression and obesity, as well as their associated hallmarks of systemic inflammation. These observations raise questions about whether certain nutritional inadequacies might play a causal role in these conditions and whether supplementation may help regulate symptom severity. Now, a recent randomized double-blind placebo-controlled clinical trial reveals that co-supplementation with magnesium and vitamin D significantly decreases depression scores and body weight in healthy women with obesity.

    The study recruited 102 women with obesity (body mass index, 30–40; ages, 20-45 years) with mild-to-moderate depression and no indication of other health issues such as hormonal dysfunction, autoimmune disease, or diabetes. The study investigators randomly allocated the women to one of four groups to receive varying combinations of a weekly soft gel containing 50,000 international units (IU) of vitamin D, a daily tablet of 250 milligrams magnesium, and/or a placebo. The groups comprised:

    1) Co-supplementation: weekly vitamin D + daily magnesium

    2) Vitamin D only: weekly vitamin D + daily magnesium placebo

    3) Magnesium only: daily magnesium + weekly vitamin D placebo

    4) Control: weekly vitamin D placebo + daily magnesium placebo

    The investigators collected participants’ blood samples at baseline and following eight weeks of supplementation. The samples revealed that while the women on average had adequate baseline serum levels of magnesium and borderline-adequate levels of vitamin D, their health outcomes and biomarkers nonetheless showed the greatest improvements as a result of co-supplementation with both micronutrients. For instance, women who received both magnesium and vitamin D lost more weight over the duration of the intervention compared to all the other groups, in the absence of any observed changes in their dietary patterns. They also showed the greatest average reduction in depression scores over time, although all participants (including controls) exhibited some degree of symptom relief after the eight-week intervention - an observation the researchers attributed in part to the placebo effect.

    The women’s blood samples revealed a similar picture, with co-supplementation outperforming all other conditions (although individual supplementation with either vitamin D or magnesium still yielded significant improvements over controls). For instance, combining magnesium and vitamin D achieved the greatest reduction in plasma levels of pro-inflammatory tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6). It also generated the highest boost in brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT1) – a protein widely known for its involvement in regulating autophagy and longevity-promoting genes.

    These findings reveal that co-supplementation with a weekly 50,000 IU dose of vitamin D and a daily 250 mg of magnesium can aid weight loss, enhance mood, and improve a host of blood biomarkers pertaining to systemic inflammation, brain functioning, and longevity. Moreover, the fact that positive health outcomes can be observed despite an absence of marked micronutrient deficiencies raises the possibility that current medical guidelines on adequate ranges of plasma levels and RDAs for vitamin D and magnesium, respectively, may be insufficiently high for optimal health outcomes.

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  • Depression is associated with muscle loss in older adults. journals.plos.org
    Aging Depression Muscle Dementia

    Sarcopenia, the loss of muscle mass with age, is related to falling, poor oral health, and chronic disease. Sarcopenia is a progressive disorder, but early interventions with diet and exercise may improve health outcomes. Authors of a new report investigated the relationship between sarcopenia progression, depression, dementia, and hypertension.

    Body composition shifts across the lifespan, with a progression toward lower muscle mass and increased fat mass after age of 60. Because fat and muscle participate in whole-body metabolism and hormone signaling, this shift in body composition contributes to the development of age-related diseases. Previous research has reported a link between sarcopenia, cognitive impairment, and depressive symptoms in older Korean men, but research is needed in additional demographic groups.

    The authors collected data from more than 750 adults aged 60 years and older living in Japan. Participants completed surveys to measure depression and dementia status and underwent a physical examination that included the measurement of blood pressure, height, muscle mass, grip strength, and walking speed. The investigators classified participants as having sarcopenia if they had low skeletal muscle index (i.e., the ratio of the muscle in a person’s arms and legs to their height), poor grip strength, and slower walking speed. They defined pre-sarcopenia as having a low skeletal muscle index with normal grip strength and walking speed. Finally, they classified participants with a normal skeletal muscle index as robust.

    Sarcopenia was associated with increased age and depression severity, but reduced hypertension. Compared to robust participants, those with pre-sarcopenia were more likely to have depression and hypertension. However, sarcopenia was not associated with dementia, which the authors noted may have been due to the small number of participants (only 49) with dementia.

    The authors suggested that future research should explore strategies for management of depression, dementia, and hypertension in the prevention of sarcopenia.

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  • Greater muscle strength reduces depression risk. www.psypost.org
    Exercise Brain Depression Muscle IL-6

    Depression is characterized by mood alterations, such as increased sadness and irritability, and physiological changes, such as decreased sleep, appetite, and sexual desire. Previous research has reported a relationship between increased muscle strength and lower depression risk in older adults. Findings of a recent study detail the relationship between muscle strength and depression risk in young adults.

    Cytokines are proteins that participate in cell-signaling. Pro-inflammatory cytokines are increased in depression and contribute to the dysfunction of neurotransmission, hippocampal neurogenesis, and stress-related nervous system activation. Skeletal muscle cells secrete a number of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-15. A previous study demonstrated a relationship between lower levels of inflammation in adolescents with increased muscle strength and decreased body fat, but the study did not measure depression risk.

    The authors included 600 female participants without depression (average age, 19 years) in their analysis who were part of a larger observational study of physical fitness and health in Chinese college students. Participants completed a survey to measure depression symptoms and a physical exam including the use of a dynamometer to measure grip strength, a proxy for total skeletal muscle strength. The authors collected these measures at baseline and at a one-year follow-up. They classified participants into one of four categories based on the amount of grip strength they gained over the one-year study period.

    At the one-year time point, about 11 percent of participants reported depressive symptoms. Participants who gained the most grip strength over the one-year study period had a 66 percent lower risk of depression compared to participants who gained the least grip strength. Participants with the greatest gains in grip strength tended to be younger and smoke less at baseline than participants with the least gains in grip strength. Finally, gains in grip strength were significantly related to body mass index (BMI) at baseline. Underweight, defined as a BMI less than 18.5, was more common in participants with the lowest gains in grip strength (43 percent), while overweight, defined as a BMI greater than 25, was more common in participants with the greatest gains in grip strength (23 percent).

    The authors concluded that increased grip strength is associated with a lower risk of depressive symptoms in young adults.

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  • Omega-3 fatty acids reduce symptoms of depression. www.kcl.ac.uk
    Omega-3 Depression IL-6

    Depression – a mood disorder that affects 322 million people worldwide – is characterized by profound sadness, anxiety, and physical complaints. People who have depression often have higher levels of systemic inflammation (which can affect brain health) compared to those without depression. Findings from a new study suggest that omega-3 fatty acids reduce symptoms of depression through their anti-inflammatory effects on the brain.

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 fatty acids derived primarily from fish. They exert a wide range of beneficial effects on the human body. Evidence from a clinical trial indicates that omega-3 fatty acids reduce symptoms of depression associated with inflammation.

    Chronic inflammation plays key roles in the development of many diseases, including cancer, cardiovascular disease, and diabetes. Inflammation in the brain impairs neurogenesis, the process of forming new neurons. Impaired neurogenesis negatively influences mood and cognitive function.

    The authors of the study conducted two experiments. In the first experiment, they pre-treated human hippocampal cells with either EPA or DHA and then exposed the cells to interleukin (IL)-1 beta, IL-6, and interferon-alpha – proteins that drive chronic inflammation. They found that EPA and DHA maintained neurogenesis and prevented programmed cell death via the effects of lipid mediators – a class of omega-3 fatty acid byproducts that influence immune health and inflammation.

    In the second experiment, the authors gave 22 people who had been diagnosed with depression either 3 grams of EPA or 1.4 grams of DHA for 12 weeks. They measured lipid mediators in the participants' blood and assessed their depression symptoms. The authors found that the anti-inflammatory lipid mediators increased in the participants' blood. They also noted that the participants' depressive symptoms decreased approximately 64 percent with EPA and 71 percent with DHA.

    These findings suggest that omega-3 fatty acids reduce the inflammation associated with depression and improve depressive symptoms. This was a very small study, however, and did not include a control group. Further research is needed to confirm these findings. Learn more about the role of inflammation in depression in this clip featuring Dr. Charles Raison.

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  • Waking just one hour earlier decreases depression risk. www.sciencedaily.com
    Sleep Depression

    Good sleep habits are important for maintaining good physical and mental health. Epidemiological studies have revealed a decreased risk of major depressive disorder in those who prefer to wake up early and go to sleep early. Authors of a report recently released studied the genetic associations between early sleep/wake preference and depression.

    Depression is a disease with multiple contributing factors that include environmental, lifestyle, and genetic influences. Untangling the web of factors contributing to late sleep preference and depression risk may help identify interventions to treat depression.

    Earlier sleep and wake times align better with typical work and social schedules, increase daily light exposure, and enhance sensitivity to rhythmic changes in brain activity, contributing to a lower risk of depression. While environmental and social factors may dictate a person’s wake and sleep schedule, genetic factors may also play a role in sleep timing preferences.

    The authors performed a genome-wide association study, which is an observational study where researchers look for associations between gene variations called single-nucleotide polymorphisms and disease prevalence. The authors collected genetic data and depression status from over 500,000 participants in the Psychiatric Genomics Consortium and United Kingdom Biobank studies to determine genetic proxies for depression. They also collected genetic and sleep data from over 700,000 participants in the United Kingdom Biobank and 23andMe research studies to determine genetic proxies for sleep time preference. Some participants wore an activity monitor to measure their sleep precisely. The researchers calculated the sleep midpoint (halfway between falling asleep and waking) and used this in their model of genetic data as well.

    Participants with an earlier sleep preference were 23 percent less likely to have depression. This decreased risk was additive for every hour that the midpoint of sleep occurred earlier in the night. That means shifting sleep one hour earlier at night and waking one hour earlier in the morning may decrease depression risk, but shifting the sleep window even earlier may decrease risk even more. The relationship between early or late waking preference and depression was significant for both physician-diagnosed and self-reported depression.

    The authors concluded that the association between genetics, sleep, and depression revealed by their study provides support for sleep interventions in patients with depression.

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  • Microbiome signatures distinguish adults with depression from healthy counterparts. www.the-scientist.com
    Microbiome Depression

    The gut and brain communicate with each other through a bidirectional signaling pathway called the gut-brain axis, which may be dysregulated in depression. Key elements of this pathway are the tens of trillions of bacteria, viruses, and fungi that comprise the intestinal microbiota. Diagnosis of depression relies heavily on clinical evaluation instead of measurement of biomarkers, often leading to misdiagnosis. Authors of a new report aimed to identify which specific microbial and metabolic biomarkers are altered in patients with depression.

    Changes to the microbes that live in the gut or the metabolites that these microbes consume and produce may be responsible for the development and severity of depression. Previous research has demonstrated that transplanting the microbiota of patients with depression into germ-free mice can induce depressive symptoms in these animals.

    The study involved 311 participants between the ages of 18 and 65 years, roughly half of whom had been diagnosed with major depressive disorder. The participants completed testing that included submission of a fecal sample to characterize the gut metagenome (sum of all DNA and RNA) and metabolome (sum of all proteins). They also completed surveys to assess depression severity, diet quality, and lifestyle habits.

    The authors reported large and consistent disturbances in amino acid metabolic metabolism in participants with depression. These disturbances may disrupt the balance of neurotransmitters, such as dopamine, glutamate, and GABA. Most of the bacterial species that were increased in patients with depression belong to the genera Bacteroides, which the authors believe is responsible for the increase in inflammatory markers found in the depression group. The authors also reported an association between select viruses in the gut and metabolites associated with depression.

    Utilizing both metagenomic and metabolic data enabled the authors to identify strong associations between altered amino acid metabolism in the gut and depression. The authors noted that these findings are preliminary and require further investigation in a larger, more diverse sample.

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  • Psilocybin use with therapy is an effective treatment for depression www.hopkinsmedicine.org
    Depression Psychedelic

    Depression affects more than 300 million people globally. Unfortunately, current treatment options are limited in their effectiveness and have side effects that reduce treatment adherence. Emerging research suggests psilocybin may be a safe and effective treatment for depression, with long-lasting results after one to two sessions.

    Psilocybin is the psychoactive compound found in hallucinogenic mushrooms of the Psilocybe genus and others. Recent research has greatly expanded the understanding of psychedelic drugs and their effects on mental illness. For example, ketamine, a short-acting anesthetic with hallucinogenic effects, is available for use in the United States to treat depression, anxiety, and post-traumatic stress disorder. Psilocybin may provide similar benefits with a lower risk of chemical addiction, however.

    Adults with depression who were not taking antidepressant medication were invited to participate in either immediate psilocybin treatment or be placed on an eight-week waitlist for treatment. Twenty-four participants completed the study treatment of two psilocybin sessions with supportive psychotherapy. The authors used a standardized rating scale called the GRID-Hamilton Depression Rating Scale (GRID-HAMD) to measure depression severity.

    One week after psilocybin treatment, participants reported a statistically significant decrease in depression symptoms (average GRID-HAMD score = 8.0, mild depression) compared to those on the waitlist (average GRID-HAMD score = 23.8, very severe depression). This effect remained four weeks post-treatment with participants in the immediate treatment group reporting average GRID-HAMD scores of 8.5 compared to 23.5 in the waitlist group. Nearly three-fourths of all participants experienced a 50 percent or greater reduction in depression symptoms by four weeks following psilocybin treatment.

    Previous research by these investigators has reported similar results in patients with cancer and depression. The authors suggested these findings demonstrate the ability of psilocybin-assisted therapy to produce large, rapid, and sustained improvement in people who have depression.

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  • Aerobic exercise benefits people with depression, especially those whose symptoms are more severe. www.inverse.com
    Exercise Depression

    Depression, often referred to as major depressive disorder in the clinical or research setting, is characterized by profound sadness, fatigue, altered sleep and appetite, and feelings of guilt or low self-worth. Although pharmaceutical treatments for depression are available, many people with depression do not respond to the medications. A new study demonstrates that aerobic exercise benefits people with depression, especially those whose symptoms are more severe.

    Previous research has demonstrated that aerobic exercise reduces depressive symptoms, but scientists aren’t sure what mechanisms drive the improvements. Two areas of interest are reward processing (the brain’s response to rewarding stimuli) and cognitive control (the ability to concentrate and make decisions).

    The intervention study involved 66 young adults (average age, 20 years) who had major depressive disorder. About half of the participants completed an eight-week program of moderate-intensity aerobic exercise, while the remainder completed an eight-week program of light stretching. The authors of the study tracked the participants' depressive symptoms throughout the study and assessed their reward processing and cognitive control before and after the intervention.

    They found that aerobic exercise reduced the participants' depressive symptoms better than light stretching. Neither form of activity had an effect on reward processing or cognitive control. However, participants whose depressive symptoms were more severe and scored high in terms of reward processing were more likely to respond to the aerobic program as opposed to the stretching program.

    These findings demonstrate that incorporating aerobic exercise programs into treatment protocols for people with depression might be beneficial in reducing depressive symptoms. Learn more about the growing body of evidence supporting the use of exercise in preventing and treating depression in this podcast featuring Dr. Rhonda Patrick.

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  • Suicidal behavior linked to Val66Met genetic variant which reduces BDNF activity www.sciencedaily.com
    Brain Depression Behavior BDNF

    From the article:

    After pooling results from 11 previous studies and adding their own study data involving people with schizophrenia, CAMH scientists confirmed that among people with a psychiatric diagnosis, those with the methionine (“met”) variation of the gene had a higher risk of suicidal behaviour compared to those with the valine variation.

    […]

    “Our findings may lead to the testing and development of treatments that target this gene in order to help prevent suicide,” says Dr. James Kennedy, director of CAMH’s Neuroscience Research Department. “In the future, if other researchers can replicate and extend our findings, then genetic testing may be possible to help identify people at increased risk for suicide.”

    As the low-functioning BDNF met variation is a risk factor for suicidal behaviour, it may also be possible to develop a compound to increase BDNF functioning, Dr. Kennedy says.

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  • Consumption of probiotics and prebiotics has beneficial effects on the gut-brain axis and mental health. www.sciencedaily.com
    Gut Microbiome Depression

    The gut-brain axis, a bidirectional signaling pathway between the gastrointestinal tract and the nervous system, is a critical component of mental health. Key elements of this pathway are the tens of trillions of bacteria, viruses, and fungi that comprise the intestinal microbiota. A recent review suggests that consuming probiotics and prebiotics has beneficial effects on the gut-brain axis and mental health.

    Probiotics are live microbes that, when consumed in the diet or in supplemental form, confer a health benefit to the host. Prebiotics are food components that support the maintenance of a healthy microbiota and create an environment that is conducive to its survival. Prebiotic fermentation by gut microbiota produces short-chain fatty acids, including lactic acid, butyric acid, and propionic acid.

    The authors of the review selected seven studies for their analysis. Each of the studies investigated the efficacy of probiotics and/or prebiotics in treating anxiety and/or depression.

    Their analysis revealed that the participants in the studies showed significant improvements in their anxiety and/or depressive symptoms. Furthermore, participants who had common comorbidities associated with their mental health conditions (such as irritable bowel syndrome), saw additional benefits due to the purported beneficial effects of probiotics/prebiotics on gut health. The authors noted several limitations of the various studies, including sample sizes, study durations, and the failure to assess long-term effects and remission risks.

    These findings suggest that probiotics and prebiotics have beneficial effects on mental health. Larger, more comprehensive studies are needed to confirm their usefulness.

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  • Plasma levels of BDNF lower in women with history of suicide attempts. www.sciencedaily.com
    Brain Depression BDNF

    Suicide is a major public health concern, claiming the lives of nearly 800,000 people worldwide each year. A history of a suicide attempt is a robust predictor of a future attempt. Findings from a 2017 study suggest that plasma levels of BDNF are a marker for suicidality.

    BDNF is a protein that plays critical roles in the creation and functioning of neurons and the ability of synapses to strengthen or weaken over time. Low BDNF levels are associated with an increased risk for depression.

    The participants in the study included 34 women with a history of suicide attempt and 39 without (average age, 33 years). The women were matched based on age, ethnicity, family income, body mass index, and cigarette smoking history. The authors of the study assessed the women’s mental health history and current status and took blood samples to determine BDNF levels.

    Thirty (88 percent) of the women who had attempted suicide had a lifetime history of major depressive disorder. Of these, 14 (40 percent) met the criteria for current major depressive disorder. The women with a history of suicide attempt had lower levels of BDNF than women without a history of suicide – a difference that was maintained even after taking into account other potential psychiatric or demographic factors. The authors of the study posited that lower BDNF levels represent a trait-like biochemical indicator of suicide risk and might be relevant for suicide prevention.

    Other biochemical indicators of suicide have been identified, as well. For example, markers of accelerated extrinsic aging have been observed in the blood of suicide completers. Age acceleration is a phenomenon that occurs when an individual’s epigenetic age exceeds their chronological age. Learn more about epigenetic aging in this overview article.

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  • Bipolar disorder patients experience generalized impaired cellular resilience and broad reductions in BDNF that may contribute to the disease www.sciencedaily.com
    Brain Depression Stress BDNF

    From the article:

    Effective neuronal plasticity also depends on neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in bipolar disorder patients and has been suggested as a hallmark of bipolar disorder. Indeed, some studies have shown that the levels of BDNF in the serum of bipolar disorder patients are reduced whenever patients undergo a period of depression, hypomania, or mania. Other studies have shown that regardless of mood state, bipolar disorder patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in bipolar disorder patients that may contribute to the pathophysiology of the disease.

    Immediate early genes:

    Immediate early genes (IEGs) are a class of genes that respond very rapidly to environmental stimuli, and that includes stress. IEGs respond to a stressor by activating other genes that lead to neuronal plasticity, the ability of brain cells to change in form and function in response to changes in the environment. Ultimately, it is the process of neuronal plasticity that gives the brain the ability to learn from and adapt to new experiences.

    One type of protein produced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment.

    […]

    in a previous study done by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found repressed in the brain of bipolar disorder patients, suggesting that when facing a stressor, the EGR3 in bipolar disorder patients does not respond to the stimulus appropriately. Indeed, bipolar disorder patients are highly prone to stress and have more difficulties dealing with stress or adapting to it if compared to healthy individuals. What the research group is now suggesting is that both EGR3 and BDNF may each play a critical role in the impaired cellular resilience seen in bipolar disorder, and that each of these two genes may affect each other’s expression in the cell. “We believe that the reduced level of BDNF that has been extensively observed in bipolar disorder patients is caused by the fact that EGR3 is repressed in the brain of bipolar disorder patients. The two molecules are interconnected in a regulatory pathway that is disrupted in bipolar disorder patients,”

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  • Seasonal variation in Nrf2 antioxidant pathway influence winter depression-like behavior in fish. neurosciencenews.com
    Depression Sulforaphane NRF2 Traditional Medicine

    Seasonal affective disorder (SAD) is a form of depression that is influenced by seasonal changes in weather and daylight. It commonly occurs in the dark, cool days of winter but can occur during other times of the year, as well. Approximately 10 percent of people worldwide experience SAD. A new study suggests that seasonal variation in the Nrf2 antioxidant pathway regulates winter depression-like behavior in fish.

    Nrf2 (short for nuclear factor erythroid 2-related factor 2) is a cellular protein that regulates the expression of antioxidant and stress response proteins. Nrf2 functions within a biological pathway called Keap1-Nrf2-ARE, where it switches on the transcription of various cytoprotective proteins that protect against oxidative damage triggered by injury and inflammation.

    The authors of the study exposed medaka, a type of fish that exhibits seasonal SAD-like differences in its behavior to either summer- or winter-like conditions. Then they examined the metabolites produced in their brains. They found evidence that winter-like conditions altered levels of 68 metabolites, some of which are associated with depression. In particular, winter-like conditions reduced levels of glutathione, a powerful antioxidant compound produced by the body’s cells. Glutathione helps prevent inflammation, a key driver in depression.

    Then the study authors analyzed gene expression in the fish and found that winter-like conditions altered signaling pathways that are implicated in depression, including Nrf2. Results of a chemical screen indicated that celastrol, a plant-based compound commonly used in traditional Chinese medicine, activated Nrf2 signaling, which in turn induced the activity of Nrf2 target genes, including glutathione.

    These findings demonstrate that celastrol could be beneficial in treating some of the symptoms associated with seasonal depression by switching on the activity of antioxidant pathways such as Nrf2. Interestingly, sulforaphane, an isothiocyanate compound derived from broccoli, is the most potent naturally occurring inducer of Nrf2 activity. Watch this clip featuring sulforaphane expert Dr. Jed Fahey in which he describes the importance of the Nrf2 pathway.

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  • Vitamin C rapidly improves emotional state of acutely hospitalized patients [1 in 5 in acute-care have scurvy levels of vitamin C] www.sciencedaily.com
    Vitamin C Inflammation Depression Immune System

    Vitamin C, which has previously been shown in some studies to reduce inflammatory markers in conditions like rheumatoid arthritis, may improve emotional state of acutely hospitalized patients.

    From the article:

    Patients administered vitamin C had a rapid and statistically and clinically significant improvement in mood state, but no significant change in mood occurred with vitamin D, the researchers discovered. […] About one in five acute-care patients in our hospital have vitamin C levels so low as to be compatible with scurvy,“ added Hoffer.

    Vitamin C, which concentrates in immune cells called neutrophils and lymphocytes at concentrations 50 to 100-times greater than plasma, play an important role in generating the so-called oxidative burst used by these cells to attack invading bacteria.

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  • Athletes who play indoor sports at risk for vitamin D deficiency. www.sciencedaily.com
    Depression Vitamin B12 Vitamin A Dairy

    Vitamin D is an essential nutrient that is involved in multiple physiological processes. Inadequate vitamin D status is associated with poor bone health, impaired immune function, and increased risk for depression. Approximately 70 percent of people living in the United States are vitamin D deficient. A recent study found that athletes who participate in indoor sports may be at high risk for vitamin D deficiency.

    Although vitamin D is available in small quantities in food, the primary source of vitamin D is via endogenous synthesis. This process occurs in a stepwise manner that starts in the skin following exposure to ultraviolet light and continues in the liver and kidneys, where the vitamin’s active form is made. Since ultraviolet light is required for vitamin D synthesis, reduced exposure to the sun or having dark-colored skin impairs vitamin D production. Plasma concentrations of vitamin D are considered optimal at 50 ng/mL or above; sufficient at 30 ng/mL to 50 ng/mL; and insufficient at less than 30 ng/mL.

    The study involved 20 male and female collegiate basketball players (average age, 20 years) of varied races and ethnicities. The majority of the players (60 percent) self-reported as African American. The authors of the study collected blood samples to determine the players' vitamin D status, assessed their body composition, and measured their skin pigmentation. The participants completed questionnaires about their sun exposure, winter travel to sunny locations, and sunscreen use.

    Then the authors allocated the players to receive one of three daily doses of vitamin D for five months, based on whether their vitamin D status was optimal (no supplementation), sufficient (5,000 IU), or insufficient (10,000 IU). Two of the participants had vitamin D concentrations in the optimal range, five in the sufficient range, and 13 in the insufficient range. More than 90 percent of those identified as insufficient had dark or olive skin tone.

    At the end of the five-month study period, one of the athletes in the non-supplemented group remained in the optimal range but the other athlete dropped to the sufficient range. Of the athletes taking the 5000 IU dose, 75 percent remained in the sufficient range, but 25 percent dropped to the insufficient range. Of those taking the 10,000 IU dose, 23 percent remained in the insufficient range, 69 percent moved into the sufficient range, and one moved into the optimal range.

    These findings suggest that collegiate athletes who play indoor sports may be at risk for vitamin D deficiency. Furthermore, high dose supplementation with 10,000 IU of vitamin D daily may be beneficial in improving vitamin D status for most players, but it falls short for some.

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  • Mental stress and lifestyle can predict lifespan. www.eurekalert.org
    Diet Aging Depression Blood Pressure Dairy

    The average life expectancy of people living in the United States is roughly 79 years. Several factors influence how long a person lives, however, such as diet, physical activity, and smoking. A new study suggests that mental stress shortens life expectancy by nearly three years.

    Mental stress can affect the immune, digestive, cardiovascular, sleep, and reproductive systems, eliciting a wide range of symptoms, including headaches, sleeplessness, sadness, anger, or irritability. Prolonged stress can promote continued strain on the body, contributing to serious health problems, such as heart disease, high blood pressure, diabetes, and other illnesses, including mental disorders such as depression or anxiety.

    The study was based on data drawn from cross-sectional health surveys conducted every five years in Finland, spanning a 20-year period between 1987 and 2007 and including approximately 35,000 adults. The study participants were generally healthy and were between the ages of 25 and 74 years. The authors of the study conducted a statistical analysis of death rates using a model that included risk factors commonly associated with longevity, such as socioeconomic background, medical history, lifestyle, lifestyle satisfaction, and biological risk factors.

    They found that some factors decreased the risk of premature death such as eating fruits and berries daily or almost daily (15 percent lower), having a higher level of education (10 percent lower), or frequent engagement in leisure-time physical activity (25 percent lower). Factors that increased risk included smoking (67 percent higher) or having diabetes (100 percent higher), both of which correlated to nearly seven years' shorter lifespan. Having high levels of stress decreased lifespan among men by nearly three years.

    To learn more about the harmful effects of stress, watch this clip featuring Dr. Elissa Epel in which she describes how stress can modulate telomere length, a marker of aging.

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  • Excess visceral fat promotes inflammation and drives cognitive decline. www.eurekalert.org
    Brain Obesity Depression Neurons Protein Metabolic Syndrome NLRP3 Visceral Fat

    Visceral fat – body fat that is stored in the abdominal cavity in close proximity to important internal organs such as the liver, pancreas, and intestines – plays a central role in the interrelationship between obesity and systemic inflammation. Excess visceral fat, often referred to as central or abdominal obesity, is a strong predictor of age-related cognitive decline. A new study in mice demonstrates that having excess visceral fat may impair cognition by activating the NLRP3 inflammasome and promoting the release of interleukin-1 beta (IL-1β).

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. Cryopyrin, also known as NLRP3, is a protein that drives the formation and activation of the NLRP3 inflammasome.

    Interleukin-1 beta is a proinflammatory protein present in many cells. NLRP3 inflammasome-driven release of IL-1β activates microglia, the brain’s resident immune cells. Microglia serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and harm.

    The authors of the study first determined that mice lacking the gene for NLRP3 did not experience visceral fat-induced brain inflammation and cognitive decline. They also determined that when visceral fat from normal, obese mice was transplanted into these mice, they exhibited higher levels of IL-1β in their hippocampus, an area of the brain associated with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation.

    To understand the effects of IL-1β on brain function, the authors of the study fed the mice a high- or low-fat diet for 12 weeks and then assessed the animals' capacity to navigate a water maze. The mice that ate the higher-fat diet experienced greater difficulties negotiating the water maze, compared to those that ate the lower-fat diet. Examination of the animals' brains revealed that the mice that ate the high-fat diet (as well as those that received the fat transplants) had weaker synapses between the neurons involved in learning and memory.

    These findings suggest that chronic inflammation driven by excess visceral fat may contribute to cognitive decline by promoting the release of IL-1β and increasing inflammation. Inflammation drives other aspects of brain dysfunction, including those associated with depression. Watch this clip in which Dr. Charles Raison discusses how a pro-inflammatory environment can contribute to the risk of depression.

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  • Antidepressant discontinuation triggers agitation, headaches, and flu-like symptoms. www.businessinsider.com
    Depression

    Nearly 25 million adults living in the United States take some form of antidepressant medication. Most antidepressants work by altering the brain’s chemistry to affect mood. Side effects of the drugs include nausea, weight gain, decreased libido, and anxiety, among others. A recent review suggests that antidepressant medication cessation is challenging for most people and may carry some risks due to discontinuation syndrome.

    Discontinuation syndrome is a phenomenon that occurs with either abrupt or tapered antidepressant drug cessation. A recent study found that more than half of people taking antidepressants report having some difficulty – sometimes severe – when attempting to stop taking the drugs. Typical symptoms of discontinuation syndrome include flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. These symptoms, which vary from drug to drug and between individuals, typically appear within a few days of drug tapering or cessation and last two or more weeks.

    The authors of the review suggested that physicians may prescribe these drugs without considering the potential side effects or without informing patients about the difficulties associated with drug cessation. They also presented a proposed schedule for tapering antidepressant drugs that varied according to drug class and brand.

    Several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating the symptoms of depression (including treatment-resistant depression), and include public health interventions, physical activity, dietary modification, meditation, sauna use, and light therapy, among others. Learn more about these approaches in our overview article on depression.

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  • Physical inactivity and sedentary behavior may be early risk factors for depression in adolescence. www.thelancet.com
    Depression

    Depression is the most common mental health disorder worldwide. Data indicate that more than 11 percent of adolescents living in the United States may have depression. Findings from a recent study suggest that low physical activity and high sedentary behavior may be risk factors for depression in adolescents.

    Symptoms of depression often first occur during adolescence, so identifying ways to prevent the condition is important. Physical activity reduces inflammation (a driver of depression) and promotes a wide range of neurogenic and neuroprotective responses that mediate depressive symptoms.

    The study was based on data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, a study of children born in England during 1991 and 1992. The authors of the study looked at associations between the amount of time spent engaging in physical activity (light, moderate, or vigorous) or sedentary behavior in 4,257 participants who exhibited depressive symptoms at 18 years of age. They measured the teens' activity levels with accelerometers at three separate time points (12, 14, and 16 years of age) to monitor changes in activity levels that typically occur during adolescence. The participants completed questionnaires about their mood to assess depressive symptoms.

    The data revealed that light activity decreased and sedentary behavior increased throughout adolescence, and these changes in activity levels were associated with increased depressive symptoms at the age of 18 years. The teens who had high or average sedentary behavior levels between the ages of 12 and 16 years had significantly more symptoms of depression compared to those who were more active. In fact, for every additional hour of sedentary behavior per day, participants exhibited an 8 to 11 percent increase in their depression symptoms score at 18 years. Conversely, every additional hour of light activity per day was associated with an 8 to 11 percent decrease in depression score.

    These findings suggest that interventions targeted at increasing physical activity and reducing sedentary behavior among teens may reduce the risk of developing depression. Watch this video in which Dr. Rhonda Patrick talks about her love of cycling for its powerful mood-enhancing effects and describes the compelling science that suggests exercise is a powerful tool for preventing or managing the symptoms of depression and mental illness.

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  • Lithium may halt progression of Alzheimer’s disease. www.mcgill.ca
    Alzheimer's Depression Salt

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. It is the most common form of dementia, affecting nearly 50 million people worldwide. One of the primary pathological hallmarks of Alzheimer’s disease is the progressive accumulation of amyloid-beta plaques in the brain. A new study in a mouse model of Alzheimer’s disease demonstrates that low-dose lithium may halt the progression of the disease by decreasing amyloid-beta plaque accumulation.

    Lithium is a drug commonly used to treat bipolar disorder and drug-resistant depression. A microdose form of lithium, called NP03, consists of lithium encapsulated in a water-in-oil microemulsion. It is absorbed in the mouth to facilitate uptake and increase bioavailability. NP03 delivers doses of lithium that are up to 400 times lower than typical formulations.

    The study involved transgenic mice that develop Alzheimer’s disease and its characteristic amyloid-beta plaque formation and cognitive impairments. The authors of the study gave the mice NP03 (40 micrograms of lithium per kilogram of body weight) five times a week for 12 weeks, to span the timeframe in which the mice would have amyloid-beta accumulation. They assessed the animals' ability to perform memory tasks and then measured levels of amyloid-beta and proinflammatory molecules in the animals' brains.

    They found that NP03 improved cognitive performance, reduced amyloid-beta burden, and reduced markers of neuroinflammation and cellular oxidative stress in the mice. These findings suggest that a microdose lithium formulation may be beneficial in reducing amyloid-beta burden in the later stages of Alzheimer’s disease progression.

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  • Yoga increases brain levels of the neurotransmitter GABA to reduce symptoms of depression. www.bumc.bu.edu
    Depression Meditation Breathing Technique

    Yoga is an ancient Indian practice that engages the mind and body through physical poses, breathing techniques, and meditation. Robust scientific evidence has demonstrated that yoga benefits both mental and physical health. A new study suggests that yoga decreases symptoms of depression by increasing brain levels of gamma-aminobutyric acid.

    Depression is a mood disorder characterized by profound sadness, altered sleep patterns, and feelings of guilt or low self-worth. It is the most common mental health disorder worldwide, affecting more than 265 million people.

    Gamma-aminobutyric acid (GABA) is a neurotransmitter produced in the brain that inhibits neural activity. Low levels of GABA are associated with increased symptoms of depression.

    The study involved 28 people between the ages of 18 and 65 years old who had depression. A variety of diagnostic tools and self-reports assessed the participants' mental health, depressive symptoms, and suicide risk. Prior to being randomized to either a low-dose or high-dose Iyengar yoga intervention group, the participants underwent magnetic resonance spectroscopy (MRS) scanning to assess GABA levels.

    The low-dose group engaged in two 90-minute yoga sessions and three 30-minute homework sessions per week. The high-dose group engaged in three 90-minute yoga sessions and four 30-minute homework sessions per week. At the end of the 12-week intervention, the participants underwent a second scan, engaged in a 90-minute yoga session, and then underwent a third scan.

    The participants in both the low-dose and high-dose groups reported that their depression symptoms improved. The MRS data revealed that participants who engaged in the low-dose yoga intervention exhibited significant increases in GABA levels between the first and third scans and between the second and third scans. The increased GABA levels were short-lived, however (lasting less than eight days after completing a yoga session), suggesting that yoga sessions should be regular and often to prevent symptoms of depression.

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  • Sleep duration may influence children's mental health. warwick.ac.uk
    Sleep Depression Mental Health

    Sleep is critical for our mental and physical well-being. Sleep deprivation increases our risk of developing many chronic illnesses, including cardiovascular disease, kidney dysfunction, hypertension, diabetes, stroke, obesity, and depression. More than a third of all adults living in the United States report regular short sleep duration. Data from a recent study suggest that children are particularly vulnerable to sleep deprivation.

    The American Academy of Pediatrics recommends that children between the ages of six and 12 years should sleep nine to 12 hours every night for optimal health. Inadequate sleep in children is associated with poor mental and physical health.

    The authors of the study analyzed structural MRI data from more than 11,000 children between the ages of nine and 11 years who were enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. They also assessed the children’s cognitive performance and mental health status. The parents of the children in the study provided information about their child’s sleep duration by answering the question, “How many hours of sleep does your child get on most nights?”

    The study revealed that children who had shorter sleep duration were more likely to experience depression and anxiety and were more likely to exhibit impulsive behavior and poor cognitive performance. The association between poor sleep and depression persisted and were observed at the one-year follow-up. In addition, the volume of the orbitofrontal cortex, prefrontal and temporal cortex, precuneus, and supramarginal gyrus regions of the sleep-deprived children’s brains were lower than children who received adequate sleep.

    These findings underscore the importance of adequate sleep for proper brain function, especially in the developing brain.

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  • High and low exercise intensity elicit different effects on brain function. www.iospress.nl
    Exercise Brain Depression Lactate

    An abundance of scientific data demonstrates that regular exercise improves overall physical health. Findings from a new study demonstrate how different exercise intensities influence brain function.

    The study involved 22 young men (average age, 27 years) who exercised regularly. Each of the men completed questionnaires and underwent tests to assess their mood, mental health, and cognitive function. Then the men engaged in either low or high intensity exercise (relative to each individual’s fitness level) on a treadmill for 30 minutes, with the two exercise periods separated by several days. The low-intensity exercise was performed at 35 percent under the lactate threshold (the point at which an increase in blood lactate concentration of 0.4 mmol/l above the baseline is observed). The high-intensity exercise was performed at 20 percent above the lactate threshold.

    Although both forms of exercise improved the men’s reported moods, resting state functional magnetic resonance imaging provided insights into how the different exercise intensities influenced brain function. Whereas low-intensity exercise activated brain networks involved in cognition control and attention processing, high-intensity exercise activated networks involved in mood.

    These findings support other data indicating that exercise benefits brain health and suggest that exercise may be a promising modality for use in improving cognitive function and in treating mood disorders.

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  • Decreasing the insulin signaling pathway and the TOR pathway increased lifespan of worms by 500 percent. www.eurekalert.org
    Aging Depression Insulin Protein

    The insulin and insulin-like signaling (IIS) pathways and the target of rapamycin (TOR) pathway are critical elements of the aging process. Findings from a new study suggest that decreasing the activity of these highly conserved pathways markedly increases the lifespan of worms.

    The IIS pathways are involved in maintaining glucose homeostasis. They facilitate the uptake of glucose into fat and muscle cells while inhibiting gluconeogenesis – the production of glucose in the liver. These pathways are dysregulated in obesity and type 2 diabetes.

    The TOR pathway senses amino acid concentrations and regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. It integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids and plays a key role in mammalian metabolism and physiology. The pathway is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers.

    The study focused on altering the activity of orthologs of these pathways (called DAF-2 and RSKS-1) in C. elegans, a type of nematode worm, which is often used in aging studies. The authors of the study introduced double mutations in the worms to block the activities of DAF-2 and RSKS-1 and conducted genome-wide translational state analysis to identify genes associated with the worms' lifespan.

    Knocking DAF-2 and RSK-1 elicited a synergistic effect that increased the lifespan of the worms by 500 percent, suggesting that regulation of these two pathways is integral to the aging process in worms. Watch this clip for learn more about the evidence that altered growth hormone and insulin signaling may improve healthspan in humans, too.

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  • Students who smoked were two to three times more likely to develop depression than students who never smoked. www.eurekalert.org
    Depression

    People who have depression often engage in harmful lifestyle behaviors such as overeating, drug abuse, or smoking. In fact, some research indicates that depression is one of the strongest contributors to cigarette smoking, especially among college students. Findings from a new study suggest the converse – that smoking may cause depressive symptoms.

    The study involved more than 2,100 male and female college students (average age, 20 years) at two universities in Serbia. The students completed questionnaires about their socio-demographic status, lifestyle behaviors, and mood. Statistical analysis revealed that students who smoked were two to three times more likely to have depression compared to students who never smoked.

    The authors of the study suggested that the mechanisms that drive this association may be related to the effects of nicotine on neurotransmitters in the brain and subsequent alterations in mood.

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  • Higher physical activity halves risk of depression in a large study of more than 395,000 adults. www.sciencedirect.com
    Exercise Depression Neurons Aerobic

    Exercise and other forms of physical activity elicit a wide range of beneficial health effects. Findings from a large study in Sweden suggest that physical activity reduces the risk of depression.

    The observational study involved more than 395,000 people who were followed over a period of 21 years. The study participants were either skiers who partook in Vasaloppet, an annual long-distance cross-country ski race held annually in Sweden (physically active), or non-skiers (physically inactive). Vasaloppet skiers typically exercise a minimum of four hours weekly and have a high level of physical fitness.

    The findings indicated that physical activity was associated with a 50 percent lower risk of developing depression during a 10-year period compared to physical inactivity. Adjustments for age, sex, and education did not alter the results.

    Some have suggested that the association between higher level of physical activity and lower risk of depression might be an artifact of reverse causation. For example, people with depression – especially those whose condition is undiagnosed – might be less likely to engage in physical activity. However, Mendelian randomization studies and data from molecular, genetic, and interventional trials suggests that the relationship is indeed causal.

    Check out our in-depth video covering exercise and depression, including data from randomized controlled trials, Mendelian randomization trials, mechanistic studies, and even ideal exercise parameters.

    An easy take-home message: Aerobic exercise at 70 to 80 percent of maximum heart rate for 40 minutes or more may be critical for boosting brain-derived neurotrophic factor (BDNF) – a growth factor that controls and promotes the growth of new neurons.

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  • Depression and suicide linked to air pollution www.theguardian.com
    Brain Depression Behavior Pollution

    Air pollution contains a myriad of toxic substances. Exposure to air pollutants is associated with poor health outcomes and increased risk of disease. Findings from a recent review and meta-analysis suggest that high concentrations of particulate matter in air pollution may increase the risk of developing depression.

    Depression is the most common mental health disorder worldwide, affecting approximately 322 million people – more than 4 percent of the global population. Between 2005 and 2015, rates of depression increased by more than 18 percent, and public health experts predict that by the year 2020, depression likely will rank second in the global burden of disease.

    Particulate matter in air pollution is a mixture of solid particles and liquid droplets. Some evidence suggests that exposure to particulate air pollutants accelerates aging.

    The authors of the review conducted a meta-analysis of 14 studies involving more than 680,000 participants living in North America, Europe, and Asia. They found that as concentrations of particulate matter increased, the risk of depression and suicide increased. Specifically, for every 10 microgram per cubic meter increase in particulate matter that is 2.5 microns or less in width, the risk of depression increased by 19 percent and risk of suicide increased by 5 percent.

    The mechanisms that drive these links may be related to increased oxidative stress and neuroinflammation as a consequence of exposure to air pollutants. These findings point to the need for improving air quality and monitoring at-risk groups living in areas where air quality is poor.

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  • Effects of hyperthermic baths on depression, sleep, and heart rate variability in patients with depressive disorder www.ncbi.nlm.nih.gov
    Depression Heat Stress Antioxidant Protein

    Depression is a mood disorder characterized by profound sadness, cardiovascular dysfunction, altered sleep patterns, and feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. Roughly a third of people who have depression fail to respond to antidepressant drugs. Findings from a clinical trial suggest that hyperthermic baths may reduce some of the symptoms associated with depression.

    Hyperthermia, a state of elevated core body temperature, stresses the body, activating molecular mechanisms that mitigate protein damage and aggregation and activate endogenous antioxidant, repair, and degradation processes. Whole-body hyperthermia is a therapeutic strategy used to treat various medical conditions, including cancer, fibromyalgia, and others. Hyperthermic baths – immersion in very hot water (40°C, 104°F) – offer a means to achieve hyperthermia.

    The randomized two-arm placebo-controlled, eight-week pilot trial involved 36 adults who had moderate depression. Half of the group was randomized to take hyperthermic baths, while the control group received a sham, low-lux green light exposure. Participants received the treatments twice weekly for four weeks.

    The hyperthermic baths involved immersion in 40°C water with the participant’s head out. Participants stayed in the water to the point of discomfort, with a target duration of 30 minutes. These 20 to 30-minute hot water baths typically increased the participants' core body temperature by approximately 1.7°C (3°F). Upon exiting the bath, the participants were wrapped in warm blankets and hot water bottles and kept warm for another 30 minutes.

    At the end of the trial, the participants who received the hyperthermic bath treatment demonstrated clinically significant improvements in measures of depressive symptoms that lasted up to four weeks after the baths were discontinued. They also exhibited improvements in sleep quality. No changes in heart rate variability were noted, however. These findings suggest that hyperthermic baths may be beneficial in treating the symptoms of depression.

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  • More than half of people suffer withdrawal effects when trying to come off antidepressants www.psypost.org
    Depression

    Depression is the most common mental health disorder worldwide. Approximately 13 percent of people over the age of 12 years living in the United States take prescription drugs to treat their symptoms of depression. Findings from a recent study indicate that many people who stop taking antidepressant drugs experience withdrawal symptoms.

    Withdrawal effects of antidepressant cessation can be mild to very severe. Symptoms include anxiety, dizziness, irritability, nightmares, nausea, “brain zaps” (electric shock sensations), and a return of depressive symptoms.

    The study’s findings were based on data gathered in an online survey of more than 800 people from 31 countries who had tried (successfully or unsuccessfully) to stop taking their antidepressants. More than half (55 percent) of the people surveyed said they experienced some difficulty in trying to quit taking the drugs. Nearly two-thirds (61 percent) reported experiencing withdrawal effects, and nearly half of these (44 percent) were described as severe. Fewer than 1 percent reported having been advised by their physician to expect withdrawal symptoms.

    These findings point to the need for providing appropriate advice to patients regarding tapering off antidepressant medications as well as the need for offering support as patients do so.

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  • Ketamine disrupts memories to help heavy drinkers cut back www.sciencemag.org
    Depression

    Addictive disorders such as alcohol abuse are often underpinned by maladaptive memories that link environmental stimuli (such as the smell and taste of an alcoholic beverage) with the feelings associated with the reward, for example. New research in the field of neuroscience demonstrates that ketamine may help reduce addictive behaviors by interfering with the formation of maladaptive memories – effectively “rewriting” them.

    Ketamine is a drug used in human and veterinary medicine to promote loss of consciousness. It is also a widely used recreational drug, commonly known as “K” or “special K.” It acts as a tranquilizer and induces a hallucinogenic, dissociative state. The FDA recently approved a nasal spray form of ketamine as a treatment for depression.

    The study involved 90 men and women living in the United Kingdom (UK) who were heavy drinkers – consuming roughly five times the recommended amount of alcohol each week per UK standards – but did not have an alcohol abuse disorder. After viewing images of beer (which promoted the urge to consume beer) the participants received an injection of ketamine or saline (a placebo). Ten days after the injection, those who received the ketamine (versus placebo) reported drinking fewer drinks and less often, an effect that lasted up to nine months post-injection. Their pre-drink anticipated enjoyment reduced as well.

    These findings suggest that interfering with the formation of maladaptive memories via the administration of ketamine may be a useful strategy for addressing addictive behaviors such as alcohol and substance abuse.

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  • Yoga increases the volume of a brain region involved in learning and memory and changes several brain regions involved in emotional regulation. www.sciencedaily.com
    Brain Depression Vegetarian Aerobic Breathing Technique

    The benefits of physical activity, especially aerobic exercise such as running, swimming, or cycling, have positive effects on brain health and function. A recent review suggests that yoga has similar effects on the brain.

    Yoga is an ancient Indian practice that engages the mind and body through physical poses, breathing techniques, and meditation. It incorporates aspects of mindfulness not commonly present in other forms of exercise.

    The authors of the review focused on 11 cross-sectional, longitudinal, or intervention studies examining the effects of yoga on the brain’s structures, function, and blood flow based on MRI, functional MRI, and SPECT (single-photon emission computed tomography). They found that yoga had beneficial effects on the hippocampus, amygdala, prefrontal cortex, cingulate cortex, and the default mode network. These areas of the brain play critical roles in memory processing, emotional control, and decision making.

    The authors identified a few confounders in their review. People who practice yoga are more likely to be physically active, non-obese, and well-educated. They are also more likely to follow vegetarian or plant-based diets. These lifestyle behaviors have been shown to have beneficial effects on brain health.

    Overall, however, the findings from this review suggest that exercise interventions like yoga may be a useful strategy to mitigate age-related changes within the brain associated with memory loss and cognitive decline.

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  • Inflammation may play a causal role in diminishing certain cognitive functions. www.birmingham.ac.uk
    Brain Inflammation Depression Protein

    Inflammation is a critical element of the body’s immune response that involves the activity of immune cells, cell-signaling proteins, and pro-inflammatory factors. Chronic inflammation, which occurs on the cellular level in response to toxins or other stressors, is implicated in the development of many chronic illnesses, including cancer, cardiovascular disease, and diabetes. Findings from a new study indicate that inflammation may be a factor in the “brain fog” that commonly accompanies chronic illness.

    The double-blinded placebo-controlled study involved 20 young men (average age, 24 years) who were injected with either a typhoid vaccine or saline. The purpose of the vaccine was to induce mild, transient inflammation, which was confirmed by the participants' blood levels of interleukin-6, a pro-inflammatory molecule.

    Six hours after the participants received their injection, three measures of their brain activity – alerting, orienting, and executive control – were assessed via electroencephalogram (EEG). The EEG results indicated that the participants' capacity for staying alert in preparation for a task was diminished post-vaccine but their other brain activities were unaffected. These findings point to a causal link between inflammation and diminished brain function and may explain why people who suffer from chronic disease often complain of difficulty concentrating or carrying out tasks.

    Interestingly, other studies have used methods similar to those used in this study to show that inflammation plays a causal role in depression. To learn more about the role of inflammation in depression, check out the FMF topic page on depression. Read the whole article or skip to the section on inflammation.

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  • Increased physical activity may significantly reduce the risk of depression, even among people who are genetically predisposed to depression. www.sciencedaily.com
    Exercise Depression Aerobic

    Approximately 322 million people – more than 4 percent of the global population – currently live with depression, the most common mental health condition worldwide. Scientific evidence indicates that roughly one-third to one-half of the risk for developing depression is due to genetic influences. A new study suggests that physical activity may reduce the risk of developing depression, even among people who are genetically predisposed to the condition.

    The study was based on genomic data and lifestyle surveys collected from the electronic health records of nearly 8,000 people enrolled in a large healthcare system in the United States. Findings from the study indicated that for every additional four hours of physical activity per week – roughly 35 minutes per day – the risk of having a new episode of depression were reduced by 17 percent. The protective effects of physical activity against depression were observed with both high- and low-intensity activities, including aerobic exercise, dance, yoga, and stretching.

    The FMF team put together a video covering the clinical and mechanistic evidence explaining why exercise may help prevent and treat depression. The video also presents evidence from Mendelian randomization studies showing that people who are genetically predisposed to depression are not less likely to engage in physical activity.

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  • Running associated with lower all-cause, cardiovascular, and cancer mortality. bjsm.bmj.com
    Exercise Cancer Heart Disease Depression Aerobic Cardiovascular

    Public health experts recommend that people get at least 150 minutes of moderate to vigorous physical activity, such as walking, running, or cycling, each week for optimal health. Running, in particular, is associated with improved aerobic fitness and cardiovascular function. A recent meta-analysis found that running, even for short periods, reduced the risk of mortality from all causes, especially cardiovascular- and cancer-related deaths.

    The authors of the study analyzed data from 14 studies of six prospective cohorts involving more than 230,000 people. The cohorts were followed over a span of 5 to 35 years. The data were adjusted for sociodemographic factors, other physical activity besides running, body fatness, health status, and unhealthy lifestyle habits such as smoking, alcohol consumption, and poor diet.

    They found that running was associated with a 27 percent lower all-cause mortality, 30 percent lower cardiovascular mortality, and 23 percent lower cancer mortality. Even the smallest amount of time spent running (less than 50 minutes per week) was linked to a significant reduction in all-cause mortality.

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  • A new study proposes exercise as a potential primary mode of treatment for mental health disorders. www.sciencedaily.com
    Exercise Depression Schizophrenia

    A new study proposes exercise as a potential primary mode of treatment for mental health disorders ranging from anxiety, depression to schizophrenia, and acute psychotic episodes.

    This small trial included ~100 patients in the medical center’s inpatient psychiatry unit and included a 60-minute structured exercise and nutrition education programs into their treatment plans. The psychotherapists surveyed patients on their mood, self-esteem, and self-image both before and after the exercise sessions to gauge the effects of exercise on psychiatric symptoms.

    Approximately 95% of patients had improved mood after exercise.

    There have been several other intervention studies showing that exercise improves mood in people with depression, improves psychosis in people with schizophrenia, and improves anxiety. The hope of this new study is that psychiatric facilities will incorporate exercise programs as a part of therapy.

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  • A single dose of psilocybin enhanced creative thinking, empathy, and subjective well-being in participants for up to seven days after use. www.tandfonline.com
    Depression Psychedelic Neurons

    A new study finds that a single dose of psilocybin enhanced creative thinking, empathy, and subjective well-being in participants for up to seven days after use.

    There have been multiple studies that have now found psilocybin appears to have a positive effect on well-being and improve symptoms of depression possibly through its effects on the serotonin receptor. Animal studies have shown that psilocybin increases neurogenesis which is the growth of new neurons in certain brain regions. Interestingly, serotonin is also linked to neurogenesis.

    I’m no expert in this field but I did interview the expert on psilocybin, Dr. Roland Griffiths. He has conducted several controlled trials on psilocybin ranging from its effects on depression to addiction. He talks in depth about how this compound can have varying effects based on dose.

    If you are interested in learning more about this research check out the episode with Dr. Griffiths.

    Episode: https://www.foundmyfitness.com/episodes/roland-griffiths

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  • A pro-inflammatory diet including fast food, processed food, and refined sugar is associated with a 40% increased risk of depression. www.clinicalnutritionjournal.com
    Inflammation Depression Protein

    A pro-inflammatory diet including fast food, processed food, and refined sugar is associated with a 40% increased risk of depression according to a meta-analysis of 11 studies.

    It is always difficult to establish causality with associative studies. With respect to inflammation and depression, there have been some studies establishing causality. For example, healthy individuals injected with proinflammatory cytokines exhibit depressive symptoms compared to those injected with a placebo.

    Moreover, inflammation can be clinically monitored by well-known biomarkers for systemic inflammation, making it amenable to potentially tracking therapeutic success: the risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein.

    To learn more about the role inflammation plays in depression, check out the animated video we put together on the role inflammation plays in depression.

    Read more
  • A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling papers.ssrn.com
    Brain Obesity Depression Saturated Fat Protein

    Obesity is associated with an increased risk of depression. The aim of the present study was to investigate whether obesity is a causative factor for the development of depression and what is the molecular pathway(s) that link these two disorders. Using lipidomic and transcriptomic methods we identified a mechanism that links exposure to a high-fat diet (HFD) in mice with alterations in hypothalamic function that lead to depression. Consumption of an HFD selectively induced accumulation of palmitic acid in the hypothalamus, suppressed the 3´, 5´-cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and increased the concentration of free-fatty acid receptor 1 (FFAR1). Deficiency of phosphodiesterase 4A (PDE4A), an enzyme that degrades cAMP and modulates stimulatory regulative G-protein (Gs)-coupled G protein-coupled receptor signaling, protected animals either from genetic- or dietary induced depression phenotype.

    These findings suggest that dietary intake of saturated fats disrupts hypothalamic functions by suppressing cAMP/PKA signaling through activation of PDE4A. FFAR1 inhibition and/or an increase of cAMP signaling in the hypothalamus could offer potential therapeutic targets to counteract the effects of dietary or genetically induced obesity on depression.

    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3188483

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  • Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila | eLife elifesciences.org
    Aging Metabolism Depression

    Abstract: Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging remains to be understood. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila, we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state. We show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis diminishes the pro-lifespan benefits mediated by PRCs-deficiency, transgenic increase of glycolytic genes in wild-type animals extends longevity. Together, we propose that epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging and that stimulation of glycolysis promotes metabolic health and longevity.

    Discussion: Aging is a complex process that can be regulated by a network of multiple mechanisms. It has been well-established that enhancing NAD+ biogenesis promotes healthy lifespan (Anderson et al., 2002; Balan et al., 2008; Mills et al., 2016). As noted, supplementation of NAD+ precursors profoundly elevates energy metabolism by increasing the expression of genes in the TCA cycle as well as glycolysis in C. elegans (Mouchiroud et al., 2013), and promotes glucose metabolism with increased flux through pentose phosphate and glycolytic pathways in mice on a high-fat diet (Mitchell et al., 2018). Therefore, it would be interesting to test whether the life-benefit effects of NAD+ might be through at least in part by the activation of glycolysis. Intriguingly, while declining intracellular NAD+ and thus increased NADH/NAD+ ratio correlate with aging (Zhu et al., 2015), our experiments in Drosophila demonstrate that increased ratios of GSH/(GSH +GSSG) and NADH/NAD+ due to enhanced glycolytic activities may provide a simple but effective way to retard aging. The oxidative phosphorylation, although produces more ATP than glycolysis, can yield intracellular ROS. The accumulation of ROS is the leading proposed cause of decline in cellular function and integrity in aging (Balaban et al., 2005). Thus, modulating H3K27me3 may reprogram bioenergetic decline during aging, which in effect reduces cellular damage and deterioration. Importantly, mammalian glycolytic genes have also been shown as PRCs targets (Brookes et al., 2012). Future investigations, including in-depth comparative analysis of PRCs and glycolytic pathway in the aging process in both flies and humans, may harness common operative mechanisms that modulate metabolic homeostasis and healthy longevity. Given the reversible nature of epigenetic pathways, this study proffers a tempting strategy against age-associated physiological decline and disease.

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  • Maternal sugar consumption, particularly from sugar-sweetened beverages, was associated with poorer childhood cognition including non-verbal abilities www.sciencedaily.com
    Brain Depression Pregnancy Development Sugar Intelligence

    Maternal sugar consumption, particularly from sugar-sweetened beverages, was associated with poorer childhood cognition including non-verbal abilities to solve novel problems, poorer verbal memory, poorer fine motor, and poorer visual-spatial/visual-motor abilities in childhood.

    The study also found that substituting diet soda for sugar-sweetened soda during pregnancy was also linked to negative effects. However, children’s fruit consumption (but not fruit juice) had beneficial effects and was associated with higher cognitive scores.

    As with any observational study, it is difficult to establish causation. However, the data was adjusted for a variety of other health and socioeconomic factors which does strengthen the data.

    Here is the long list of the health/lifestyle factors that the data were adjusted for: maternal age, pre-pregnancy BMI, parity, education, smoking status during pregnancy, maternal prenatal fish intake (the mean of the first and second trimesters), household income at enrollment, and the child’s sex and race/ethnicity,child’s birth weight, maternal marital status, intelligence, depression during pregnancy, pre-pregnancy physical activity levels, Western or prudent dietary pattern (calculated without fruits and sugar beverages), breastfeeding duration, paternal age and education, and HOME-SF score.

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  • Interlinking the kynurenine pathway, obesity, depression, and inflammation. www.ncbi.nlm.nih.gov
    Abstract Obesity Inflammation Depression

    [Abstract]

    Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity.

    This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases.

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  • Depression may be treated by lowering inflammation. www.telegraph.co.uk
    Inflammation Depression Protein

    The risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein (inflammatory biomarker). Inflammation is caused by a variety of factors including emotional/social stress, poor diet, sedentary lifestyle, poor sleep, and more. While it’s very possible (likely?) that there may be more going on with depression than just inflammation, I believe it’s an incredibly useful lens through which to look at promising avenues to treat or prevent it. We may find in years to come that measuring inflammation may also be useful as a way to track the therapeutic success of a whole lifestyle intervention intended to treat an important biological root cause. Inflammation isn’t just an important component (seemingly) of mental health, however… it’s also an important source of DNA damage, which is a fundamental mechanism of aging itself. This is one reason why it shouldn’t surprise us that lower inflammation is also associated with longer lifespan, prolonged physical function and also cognitive abilities in old age. In fact, it has been suggested that inflammation may be the most important driver of successful longevity that actually increases in its importance with advancing age. My team put together a short animated video explaining how inflammation plays a causal role in depression. I hope you check it out and perhaps we will also find that it’s also visually interesting enough to reach a wider, interested group of people. Animated video: https://www.youtube.com/watch?v=fqyjVoZ4XYg

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  • Brain inflammation found to be 30% higher in people suffering with obsessive-compulsive disorder. www.eurekalert.org
    Brain Omega-3 Inflammation Depression Immune System Anxiety Iron

    There’s very good evidence for systemic inflammation being implicated in mental disorders more generally, but also depression specifically. See the FoundMyFitness video entitled “The Underlying Mechanisms of Depression” to learn about some of the interesting experiments establishing the connection between immune dysfunction and symptoms of depression.

    This study, however, seems to suggest that people with obsessive-compulsive disorder actively have 30% higher brain-related inflammation.

    FTA:

    A chemical dye measured the activity of immune cells called microglia, which are active in inflammation, in six brain areas that play a role in OCD. In people with OCD, inflammation was 32 per cent higher on average in these regions. Inflammation was greater in some people with OCD as compared to others, which could reflect variability in the biology of the illness. […] Another notable finding from the current study - a connection between resisting compulsions and brain inflammation - provides one indicator. At least nine out of 10 people with OCD carry out compulsions, the actions or rituals that people do to try to reduce their obsessions. In the study, people who experienced the greatest stress or anxiety when they tried to avoid acting out their compulsions also had the highest levels of inflammation in one brain area. This stress response could also help pinpoint who may best benefit from this type of treatment.

    In light of the fact that we now know the body’s immune system is afforded direct access to the brain via a network of lymphatic vessels in the meninges, it puts managing systemic inflammation in a whole new light.

    While we may be a long way away from finding a “cure” for people suffering from these disorders, it does make multi-pronged inflammation reduction approaches that much more appealing.

    This could possibly include…

    … and yes, possibly targetted drugs as well. The point is, by establishing inflammation as a missing link in these disorders it opens up a lot of different possible “treatments” that might have a cumulative effect! Interesting times.

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  • Daily tea consumption (green, black or oolong) was associated with a 50% reduced risk of cognitive decline. www.sciencedaily.com
    Brain Alzheimer's Aging Depression Dementia Caffeine Antioxidant Dairy

    Daily tea consumption (green, black or oolong) was associated with a 50% reduced risk of cognitive decline and a 86% lower risk in people genetically predisposed (ApoE4 gene) for Alzheimer’s disease.

    The mechanism for the cognitive benefit is unclear and may include catechins, theaflavins, thearubigins and L-theanine which are all anti-inflammatory and have antioxidant activity. However, caffeine itself cannot be ruled out as a contributing factor as well.

    While this data is an association and does not prove causation, the data was adjusted for many different factors that affect health and it still found the 50% and 86% reductions. The health factors that were adjusted for in the analysis included age, gender, education, smoking, alcohol consumption, body mass index, hypertension, diabetes, heart diseases, stroke, depression, ApoE4, physical activity, social and productive activities, vegetable and fruit consumption, fish consumption, and daily coffee consumption.

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  • People with the highest fiber intake had ~80% greater chance of living long & healthy life out of all other dietary factors looked at. www.sciencedaily.com
    Gut Aging Microbiome Inflammation Depression Immune System Carbohydrates

    other factors including total carbohydrate intake, glycemic index, glycemic load, and sugar intake. Successful aging was defined as including an absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases including cancer, coronary artery disease, and stroke.

    The gut is a major source of inflammation and also the major regulator of the immune system. Fermentable fiber feeds the beneficial bacteria in the gut which then prevents them from being forced to cannibalize the gut barrier (which causes inflammation) and it allows them to produce signaling molecules (short chain fatty acids) which make the immune system better. Also, many foods that contain fiber such as vegetables and fruits also have many important micronutrients and other plant compounds that play a role in successful aging. For more on the importance of fiber in successful aging watch my interview with the authors of The Good Gut, Drs. Justin and Erica Sonnenburg: https://youtu.be/gOZcbNw7sng

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  • The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system journals.cambridge.org
    Abstract Brain Depression Stress Behavior Mental Health Cannabinoid Dairy

    Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1–selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation. These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.

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  • [TIMELINE] Joe Rogan Experience #502 with Dr. Rhonda Patrick www.foundmyfitness.com
    Omega-3 Depression Insulin Fatty Liver Vitamin A Isothiocyanates Antioxidant Protein Dairy Blood Sugar Metabolic Syndrome Myrosinase

    This is the full minute-by-minute timeline for JRE #502. Click here to watch the video on YouTube.

    • 00:02:42 - Starts off by talking about kappa opioids and dynorphin and how you feel stress right before important events
    • 00:04:24 - Joe talks about how great you feel after a competition (fight)
    • 00:05:35 - Talks about how capsaicin in spicy food also induces a release of endorphins via dynorphin agonization
    • 00:06:22 - Briefly mentions sauna/hyperthermic conditioning article featured on 4-Hour Workweek
    • 00:06:45 - Description of hormesis and how this is part of the mechanism of action for things like EGCGs in green tea and polyphenols in fruit.
    • 00:07:50 - Joe brings up that Rhonda suggested mycotoxin might be hormetic previously, Rhonda clarifies this was entirely and highly speculative. Includes jazz hands.
    • 00:08:45 - Joe mentions that his best decisions are made after a good workout. He does not trust his judgment if he has not got a good workout in.
    • 00:09:15 - Discussion of exercise and how it grows new brain cells (neurogenesis) via the BDNF pathway and how the growth of new brain cells allows you to forget other memories.
    • 00:11:20 - Joe mentions how people in highschool that never left your small hometown sometimes remember stuff you don’t. Get out of the small town, highschool friends. Make new memories.
    • 00:12:00 - Talks about how amygdala activation from either extreme excitement or fear increases episodic memory.
    • 00:12:15 - Talks about her new paper and how serotonin plays a role in brain function/dysfunction, behavior, and episodic memory.
    • 00:13:38 - Joe brings up MDMA burnout and suggests serotonin’s role in episodic memory may be why the MDMA/roller burnout stereotype exists
    • 00:15:00 - Explanation of what receptor down-regulation is and why it adds enormous complexity to understanding the effects of drugs, like SSRIs.
    • 00:16:27 - Discussion of “Serotonin Syndrome.”
    • 00:17:22 - Most serotonin is actually made in the gut, not the brain.
    • 00:17:44 - Discussion of how the genes that convert tryptophan to serotonin found in the gut (TPH1) and in the brain (TPH2) are show a characteristic nucleotide sequence known as a “Vitamin D Response Element” that seems to indicate, for the most part, that Vitamin D represses the production of serotonin in the gut (TPH1) and increases serotonin in the brain (TPH2). This is the subject of Rhonda’s most recent academic paper: “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”
    • 00:18:45 - Serotonin made in the gut has been shown to cause gastrointestinal inflammation by activating T cells and causing them to proliferate. Knocking out TPH1 in a mouse model of colitis ameliorates the inflammation associated with the disorder.
    • 00:21:55 - Theoretical vitamin D mechanism may play a role in the development of autism by depriving developing foetus of serotonin that serves as an “early brain morphogen” when mothers are deficient in vitamin D.
    • 00:23:45 - Autism appears to be developing early in utero (during pregnancy) and seems to show indications of being at least partially related to environment.
    • 00:24:00 - Estrogen can activate TPH2 in lieu of Vitamin D and thus may explain why autism is predominantly found in males.
    • 00:24:30 - Gut inflammation is common among autistics.
    • 00:24:45 - Explains 5-HTP bypasses the normal tryptophan hydroxylase (TPH) conversion, and because of that it can be converted into serotonin more rapidly… but (hypothetically) too soon and in the gut instead of the brain.
    • 00:25:35 - Tryptophan gets transported into the brain in order to be converted into serotonin by tryptophan hydroxylase (TPH2) but competes with BCAAs for transport into the brain, which are transported preferentially.
    • 00:25:55 - Tryptophan is less abundant of an amino acid than branch chain amino acids like leucine in protein.
    • 00:26:55 - Joe asks Rhonda if T cell activation/proliferation in the context of TPH1 has relevance for AIDS.
    • 00:28:00 - Joe relates how “New Mood” (Onnit’s product) was originally called “Roll Off.”
    • 00:30:30 - Joe quips that it was recently experimentally validated in mice that DMT is produced in the pineal glands of mice during sleep, goes on to talk about speculation that near death experiences relating to altered perception from endogenous DMT release.
    • 00:35:10 - Plays a video of a jaguar eating hallucinogenic plants.
    • 00:37:20 - Talks about monoamine oxidase
    • 00:38:40 - Merits of “theoretical papers” (like “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”)
    • 00:39:37 - 70% of population is vitamin d deficient. Segways to awesome infographic created by @tjasonwright which covers a ton of the basic facts about vitamin D.
    • 00:43:02 - BaadBobby’s Dad turned Joe onto TA-65. TA-65 has been shown to increase telomere length, but theres a guy who sued the company producing it. Anecdotally, BaadBobby’s dad had improvements in eyesight.
    • 00:45:00 - Explanation of what telomeres are.
    • 00:48:50 - Special enzyme telomerase rebuilds telomeres, but it’s found mostly only in stem cells… and more importantly: cancer cells. Cancer cells hijack this telomerase normally reserved for stem cells to live forever. Strangely… Mice, unlike humans, actually express telomerase in all of their cells and don’t have telomere shortening.
    • 00:50:10 - Werner’s syndrome involves excessive telomere shortening.
    • 00:53:33 - Explains how aging is a function of DNA damage and discusses DNA damage assay (test) that Rhonda performs.
    • 00:55:30 - Obesity link to increased DNA damage.
    • 00:56:50 - Talks about TA-65’s active ingredient in a study was shown to genuinely increase telomerase activity and length of telomeres.
    • 00:58:22 - TA-65 study showed a 40% increase in telomere length in white blood cells in some humans studied.
    • 00:58:44 - Second study on TA-65 using special mouse model from well-known lab also showed re-activation of telomerase, and even began reversing aging of their tissues. Mice notably did not get cancer. Reinforces findings of first study.
    • 01:01:30 - Still concerned TA-65 could encourage the growth of pre-cancerous cells.
    • 01:02:00 - Joe brings up alkalizing diet for cancer prevention (he’s a skeptic).
    • 01:03:05 - Bad bacteria in gut is affected by pH.
    • 01:06:20 - Joe brings up argument that sugar consumption affects growth of cancer.
    • 01:07:50 - Explains because cancer cells become glycolytic which is why people fixate on sugar as a potential cancer cell.
    • 01:08:40 - Rhonda mentions that taking away glucose, but allowing continued presence of glutamine allowed cancer cells to keep growing in vitro.
    • 01:09:50 - Folic acid needed in the absence of cancer because you need it to build new DNA – but this is a problem if you do have a cancer because it can be a bad thing for the same reasons (folic acid needs to produce DNA because cancer cells are highly proliferative).
    • 01:12:00 - Glucosinolates are cleaved into isothiocyanates by myrosinase which is de-activated by heat. Isothiocyanates are potent anti-cancer agents. Recent anti-kale stuff is, in a way, anti-isothiocyanates. Additionally, if you boil kale and de-activate myrosinase you’re actually decreasing the amount of isothiocynates by removing myrosinase.
    • 01:14:00 - Kale thyroid stuff is probably only relevant if you’re very deficient in iodine – probably better to continue getting your isothiocyanates for cancer preventative reasons rather than sweating this stuff.
    • 01:16:35 - Rhonda mentions tumor suppressor genes, which are activated by hormesis (good stress triggered by things like isothiocyanates).
    • 01:19:20 - Joe brings up Dave Asprey’s take on boiling kale to remove oxalic acid.
    • 01:20:10 - Spinach that was either raw, boiled, fried, or frizzled and found that raw and boiling doesn’t affect absorption, but it did very modestly affect minerals in kidneys if raw… didn’t seem to cause kidneys stones (in mice). Probably requires absurd amounts of spinach to cause kidney stones. Just not convinced that it’s bad to eat spinach or kale raw.
    • 01:20:20 - Vegetables do make compounds that are sort of “bad for you” but have a net positive effect because they induce hormesis.
    • 01:24:33 - JRE consensus of #502 –eating raw spinach and kale is good for you.
    • 01:25:10 - Joe throws a curveball by bringing up a documented case of presumed oxalate induced nephropathy (kidney disease) from 1985 to 2010 – only 36 patients documented by paper. Only three patients really suspected that it was caused by raw juicing.
    • 01:27:30 - Discussion of vegetable smoothies begins here – specifically using these powerful blenders which leave the fiber in, not juicing.
    • 01:28:45 - Brock Lesnar allegedly ate nothing but meat, got diverticulitis.
    • 01:29:07 - Putrefying bacteria make nasty smelling hydrogen sulfide farts, use sulfate as source of energy. Needs heme from red meat as a cofactor for creating hydrogen sulfide. Hydrogen sulfide prevents human gut cells from making energy (ATP), and thus causes break-down of gut-mucus barrier.
    • 01:32:25 - Brings up episode with Dr. Offitt on Bryan Callen’s podcast. Offitt claims vitamins and antioxidants cause cancer.
    • 01:35:20 - Beginning of general debunking of Offitt’s claims.
    • 01:36:05 - Randomized double-blind placebo controlled trials are awesome, but using them for nutrition research and expecting the design to perform as effectively is misguided.
    • 01:37:30 - Everyone has different levels of vitamins & minerals in their body, but baseline for drugs is always the same: zero. This is an important fundamental difference.
    • 01:42:20 - Years of research has to be published even if results aren’t great, and this requires salesmanship. This affects some of the misleading presentation of research.
    • 01:43:04 - Joe brings up highly publicized and contentious “Enough is Enough” editorial which was covered at length in podcast #459.
    • 01:46:28 - Begin discussion of Vitamin E prostate cancer study (the SELECT trial).
    • 01:47:35 - Comparison of Alpha Tocopherol & Gamma Tocopherol forms of vitamin E. Alpha tocopherol serves predominantly as an antioxidant, gamma tocopherol serves as an anti-inflammatory agent by reducing reactive nitrogen species (also an anti-oxidant activity). Alpha tocopherol doesn’t serve the same anti-inflammatory behavior, and this is important because inflammation is a cancer initiator (among other things), and excessive alpha tocopherol consumption depletes gamma tocopherol from tissues.
    • 01:50:45 - Study on prostate cancer found that alpha tocopherol and selenium didn’t affect cancer incidence at 5-year followup but at 7.5 year follow-up cancer risk for prostate cancer shot up from taking 400 IU of alpha tocopherol (vitamin E) per day. Importantly, what was found at the 5-year followup was that (relative to baseline) gamma tocopherol was depleted from the tissues. Those who weren’t deficient selenium (& were supplementing) that took the 400 IU of alpha tocopherol didn’t experience the increase in prostate cancer incidence.
    • 01:52:05 - One of the proteins selenium is for is important for preventing damage from reactive nitration products. Nitration damage can cause cancer. This is an interesting novel mechanism by which a depletion of gamma tocopherol through a combination of inflammation and an increase in reactive nitratition products might be responsible for the increase cancer incidence found in this study.
    • 01:54:00 - Discussion of vegetable smoothie as a good source of vitamin E, and also natural magnesium (from chlorophyll molecules – this was mentioned in JRE #459)
    • 01:54:45 - Mixed tocopherol Vitamin E supplements exist which aren’t quite as high dose as 10x the RDA (400 IU) like used in those studies.
    • 02:01:18 - RDA for Vitamin D is 600 IU a day. One study showed that 4,000 IU was more appropriate for actually adequately fixing without toxicity in deficient populations. 2000 to 4000 IU of vitamin D is probably a good range except for in cases of severe deficiency.
    • 02:03:18 - Offit lumped omega-3 in with “antioxidants that cause cancer”, but this is misleading given the fact that randomized controlled trials have shown that omega-3 supplementation actually reduces all-cause mortality.
    • 02:03:39 - 1500 IU of vitamin D a day has been correlated to a 17% reduced cancer risk (overall).
    • 02:04:15 - Study based off of self-reported questionaire found that women who took vitamins (supplements) - on a daily basis had the longest telomeres.
    • 02:05:45 - She tries to get all her micronutrients, as much as she can, from her diet including vegetable smoothies, fish, etc. However, in addition to her diet she takes: omega-3 fatty acids, vitamin D, a multi-vitamin which has selenium and other trace elements, iodine, B-complex.
    • 02:06:30 - B vitamin deficiency is less common due to fortification. However, she supplements B vitamins anyway because changes in mitochondrial membrane rigidity that occurs with age alters the binding affinity (as represented by the constant kM) of important proteins needed to generate energy in the form of ATP which are embedded in the mitochondrial membrane. The Ames lab has partly demonstrated, however, that increasing the concentration of B vitamins compensates for these age related changes caused by changes in the confirmation (shape) of the proteins.
    • 02:08:00 - Rhonda increasingly prefers Swanson brand vitamins, but gets omega-3 from nordic naturals.
    • 02:10:00 - B vitamins are probably less dangerous because they’re water soluble (excess is more readily excreted, similar to Vitamin C)
    • 02:11:00 - Plant form of omega-3, ALA, converts to EPA (normally found in fish) fairly inefficiently at a rate of about 5%.
    • 02:12:13 - Microalgae oil is a good alternative to flaxseed oil if you’re trying to meet EPA/DHA needs and avoiding fish oil for one reason or another.
    • 02:13:30 - Omega-3 EPA is a potent anti-inflammatory, and DHA is a really component of your cell membranes – and makes up about 40% of the brain.
    • 02:13:54 - She takes about 6 pills of her omega-3, which amounts to ~3 “servings” of 800mg of EPA, and 600mg of DHA. (2400 and 1800 mg respectively)
    • 02:15:28 - Omega-3 EPA, which can be bought more concentrated for its particular effects, interacts with the arachnidonic acid pathway to reduce inflammation. The arachnicdonic acid pathway is responsible for creating prostaglandins which activate the COX pathway.
    • 02:16:05 - 2 grams of EPA per day has been shown to reduce C-reactive protein (CRP), which is a generalized systemic marker for inflammation but is most well known for its use to asses risk of cardiovascular disease.
    • 02:17:45 - Omega-3 fatty acids are prone to oxidation. Refrigeration helps with this, however. Also check if they go rancid by smell, if smell bad then probably rancid.
    • 02:20:00 - Talks about krill oil. Joe lists off a bunch of points from a Mercola article, and Rhonda points out it’s talking about ordinary effects of omega-3 and suggesting they may not be unique to krill oil.
    • 02:27:29 - Recommends Linus Pauling Institute for good, objective source of supplemental micronutrient reviews.
    • 02:28:35 - Brief mention of WellnessFX as a useful tool for getting a broad spectrum blood test checking for relevant markers for vitamins, minerals, inflammation, etc.
    • 02:31:00 - Whackiness of homepathy discussed. Homeopathy makes use of official sounding measuring system that measures an absurd amount of dilution that actually guarantees that what you’re taking doesn’t actually include the active ingredient the supplement is being marketed for.
    • 02:33:25 - Discusses how emerging research showing wisdom teeth has dental pulp stem cells in them and they offer promise for eventually being used as a source of cells that can be differentiated into things like brain cells. You can bank children’s teeth or adult wisdom teeth. Usually like $625 to “process” a tooth, and around $125/year to store it.
    • 02:36:16 - They can now take fibroblast cells from skin, the sort that you slough off everyday, and add transcription factors to turn them into “pluripotent” stem cells which can turn into brain cells or liver cells.
    • 02:37:35 - Joe brings up study where they took blood of young mice, injected it into old mice, and found the older mice experienced tissue regeneration. Inverse was also true: injecting young mice with old mouse blood increased rate of aging.
    • 02:38:54 - Human “methylome” now being studied which is revealing a specific pattern of methylation in DNA that can be used to actually identify the chronological age of people. Since epigenetics is obviously playing an important role in age, this is another promising area of new inquiry that may eventually reveal how to reprogram our cells to “be younger”. Cancer cells show a methylation pattern that is ordinarily associated with old age and are clustered around areas related to DNA repair, mitochondrial metabolism, antioxidant genes (all areas associated with aging).
    • 02:43:12 - Scientists are now able to take renal cells excreted in urine and turn them into pluripotent stem cells
    • 02:43:45 - Rant about lack of funding in science reducing room for creativity/moonshots.
    • 02:48:40 - Joe brings up new studies showing its possible to create artificial blood for transplant.
    • 02:50:06 - Inactivating insulin growth factor in c. elegans worms doubles their lifespan from about 15 to 30 days.
    • 02:52:40 - Joe asserts (reasonably so) that by age 200 he will most likely be a wizard.
    • 02:55:42 - Joe relates the fact that he’s actually been evacuated twice due to large fires in his neck of the woods of L.A.
    • 02:57:45 - Rhonda begins plug of iPhone app, website, Twitter, and podcast.
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