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Mental Health

Episodes

Posted on April 2nd 2022 (about 3 years)

Darya Rose talks about her 10 day silent retreat.

Posted on April 2nd 2022 (about 3 years)

In this clip, Dr. Ashley Mason describes what drives insomnia and how the condition can be treated.

Posted on April 2nd 2022 (about 3 years)

In this clip, Dr. Ashley Mason describes how mindfulness, a cognitive behavioral strategy, can help mitigate harmful behaviors like overeating and smoking.

Topic Pages

  • Omega-3 fatty acids

    Omega-3 EPA/DHA integrate into neuronal membranes, modulating fluidity, neurotransmitter signaling and neuroinflammatory pathways implicated in depression and mood regulation.

  • Salmon roe

    DHA and EPA in salmon roe attenuate neuroinflammation, stabilize neuronal membranes, and modulate serotonergic signaling, supporting mental health.

News & Publications

  • 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

  • Cold-water immersion has surged in popularity, with ice baths and cold showers touted as shortcuts to better health. Advocates claim it improves mood, sharpens focus, and speeds up recovery. A recent study found that while cold exposure temporarily increased inflammation, it reduced stress 12 hours later, improved sleep, and reduced sick days.

    Researchers conducted a systematic review and meta-analysis of 11 studies involving more than 3,100 healthy adults investigating the effects of cold-water exposure on mental and physical health markers, including mood, stress, immunity, inflammation, and sleep quality. Participants in the various studies took cold showers or ice baths at temperatures between 7°C (45°F) and 15°C (59°F) for at least 30 seconds.

    The analysis revealed that inflammation spiked immediately after immersion and stayed elevated for an hour. Interestingly, stress levels dropped 12 hours later but remained unchanged at other time points. Cold exposure did not immediately boost immune function, but a separate analysis linked cold showers to a 29% drop in sickness absence. Participants reported better sleep and overall well-being but no changes in mood.

    These findings suggest that cold-water immersion may offer short-term stress relief and potential immune benefits, with highly time-dependent effects. The effects of cold exposure may be due to hormesis—a compensatory defense response that conditions the body against future stressors. Learn more in Aliquot #97: Thermal Stress, Part II: Unveiling the Power of Cold Exposure on Health and Performance

  • 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.

  • 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.

  • Anxiety disorders affect millions of adults each year, and emerging evidence suggests that diet influences symptoms. Oxidative stress likely contributes to anxiety, but antioxidants may help counteract its effects. A recent study found that people with severe anxiety consumed fewer antioxidants than those without anxiety and that increasing antioxidant intake substantially reduced anxiety symptoms.

    Researchers first compared the daily antioxidant intake of adults with and without severe anxiety. Then, they carried out an interventional study, providing 40 adults with severe anxiety with an antioxidant-rich beverage daily for six weeks to assess changes in anxiety levels. The beverage contained 15 grams of green tea (containing polyphenols and tannins), 3 grams of cinnamon powder (containing cinnamaldehyde and proanthocyanidins), and three lemon slices (containing flavonoids and vitamin C).

    They found that people with severe anxiety had considerably lower daily antioxidant intake than those without. However, after six weeks of higher antioxidant intake, participants experienced a substantial reduction in their anxiety levels.

    This was a small study, but its findings suggest that dietary antioxidants play a role in managing anxiety, potentially offering a simple, nutrition-based lifestyle approach to reducing anxiety symptoms. Learn about other lifestyle strategies for managing anxiety in Aliquot #8: Lifestyle interventions for depression and anxiety.

  • Cold exposure offers surprising health benefits, and emerging evidence suggests that whole-body cryotherapy enhances wellness and even improves sleep. A recent study found that five days of daily cryotherapy improved mood, reduced anxiety, and enhanced sleep quality in healthy young adults.

    The study involved 20 physically active young adults who underwent five consecutive days of cryotherapy sessions and five consecutive days of no cold exposure. The cryotherapy sessions lasted five minutes in a chamber cooled to -90°C (-130°F). Researchers used actimetry, brain activity recordings, and self-reported questionnaires to measure the participants' sleep patterns. They also assessed their mood, anxiety, and heart rate variability during the nights following each condition.

    Participants who underwent cryotherapy reported a 9% improvement in subjective sleep quality, with women benefiting the most. The cryotherapy sessions also increased slow-wave sleep, the most restorative sleep phase, by an average of seven minutes per night. No substantial changes were observed in heart rate variability or other sleep parameters.

    These findings from this small study suggest that repeated whole-body cryotherapy is a promising strategy for improving slow-wave sleep and psychological well-being, especially for women. Learn more about cold exposure in our comprehensive overview article.

  • 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.

  • Vitamin D plays a crucial role in the early development of dopamine-producing neurons, shedding light on the potential neurodevelopmental origins of schizophrenia. Abnormalities in dopamine signaling are at the heart of this complex mental health disorder, and a recent study suggests that vitamin D deficiency during pregnancy influences these pathways, increasing the risk of schizophrenia in offspring.

    Researchers examined nerve growth, synapse formation, and dopamine release in various dopamine-producing cells exposed to vitamin D over time. They focused on SH-SY5Y cells—which can mature into dopaminergic (dopamine-releasing) neurons—and other brain cells.

    They found that vitamin D increased neuron outgrowth and branching in dopaminergic cells, enhancing the production and release of dopamine. It also altered the expression and distribution of critical presynaptic proteins involved in dopamine release, further supporting its role in dopaminergic development.

    These findings suggest vitamin D is crucial for developing and maturing dopamine-producing neurons. They provide new insights into how maternal vitamin D levels might influence the risk of schizophrenia in offspring by affecting early dopamine signaling pathways. Evidence suggests that vitamin D synergizes with omega-3 fatty acids to support neurodevelopment. Learn more about this relationship in this peer-reviewed article coauthored by Dr. Rhonda Patrick.

  • Loneliness, a pervasive emotional state that adversely affects mental and physical health, increases the risk of many chronic health disorders, including cardiovascular diseases. A recent study found that loneliness increases the risk of stroke by as much as 56%.

    Researchers analyzed data from the Health and Retirement Study, which included adults aged 50 years or older who were stroke-free at the start. Participants ranked their loneliness on a scale of three to nine, with scores above six considered “high.” Researchers tracked the incidence of stroke among the participants over 10 to 12 years.

    They found that higher loneliness scores at baseline were associated with an increased risk of stroke, with a one-point increase in loneliness score corresponding to a 5% higher likelihood of stroke. Participants with high loneliness scores were 25% more likely to experience a stroke, even after accounting for social isolation without depressive symptoms. Notably, participants with consistently high loneliness over time were 56% more likely to experience stroke than those with consistently low loneliness.

    These findings suggest that chronic loneliness is a major risk factor for stroke, independent of depressive symptoms or social isolation. Addressing loneliness may be crucial for stroke prevention, and regular assessments of loneliness in clinical settings could help identify people at higher risk.

    Interestingly, sleep and loneliness are inherently linked, and poor sleep increases the risk of stroke. Not getting enough sleep triggers the onset of a “loneliness phenotype,” driving people who are sleep-deprived to avoid social interaction. Learn more about the effects of sleep on feelings of loneliness in this clip featuring Dr. Matt Walker.

  • 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.

  • Technology enriches our lives, enhancing communication, improving healthcare, and providing access to vast amounts of information. However, the amount of time we spend on the devices that deliver that technology may be harmful, especially for young children. A recent study found that two hours or more of daily screen time among preschoolers lowers psychological well-being.

    Researchers analyzed data from the 2018-2021 National Survey of Children’s Health, focusing on children aged six months to five years. Primary caregivers reported the children’s daily screen time and provided information about their flourishing and externalizing behaviors – indicators of psychological health.

    They found that over the four-year study period, 50.9 percent of the children had high screen time, defined as one or more hour daily for children aged six months to one year and two or more hours daily for children aged two to five years. The percentage of children with high screen time increased to 55.3 percent during the pandemic in 2020 and was even higher among children living in poverty (60.9 percent). More than two hours of daily screen time was linked to less flourishing and more externalizing behaviors for children aged three to five years.

    Flourishing refers to the presence of positive emotions, relationships, and adaptive functioning. It plays a crucial role in reducing the risk of antisocial behaviors later in life. Externalizing behaviors, such as hyperactivity and aggression, reflect maladjustment to the external environment. They can hinder learning and relationships and may lead to juvenile delinquency and adult violence.

    These findings suggest that excessive screen time may harm psychological well-being in preschool-aged children. Parents and caregivers should be mindful of screen time limits to promote better mental health outcomes for young children. Learn more about the effects of screen time on children and teens in this short video featuring Dr. Rhonda Patrick.

  • Delirium is a sudden and severe state of confusion that can affect attention and cognitive function. It is particularly common in older adults after surgery or hospitalization, increasing their risk of death, institutionalization, and dementia. A 2022 study found that structural integrity of the anterior midcingulate cortex may predict and mitigate the risk of postoperative delirium.

    The study involved 93 cognitively normal older adults undergoing elective surgery. Researchers divided the participants into two groups based on their performance on neuropsychological tests: “SuperAgers” (those whose cognitive function was comparable to that of young adults) and those whose cognitive function was typical for their ages. Participants underwent magnetic resonance imaging (MRI) to assess the structural integrity of various brain regions.

    The researchers found that none of the SuperAgers experienced postoperative delirium, whereas 20 percent of the typical older adults did. Those who did not experience postoperative delirium exhibited enhanced structural integrity of the anterior midcingulate cortex.

    The anterior midcingulate cortex is a brain region involved in a wide range of cognitive and motor functions. This critical area grows in response to activities that require considerable effort, such as exercise. Here’s what Dr. Andrew Huberman, our recent interview guest, had to say about it.

    These findings suggest that greater structural integrity of the anterior midcingulate cortex protects against delirium and predicts cognitive resilience in older adults. They also align with other evidence demonstrating that SuperAgers exhibit greater cortical thickness in the anterior midcingulate cortex and lower incidence of Alzheimer’s disease. Learn more about the anterior midcingulate cortex in this episode featuring Dr. Andrew Huberman.

  • Psychosis is a neuropsychiatric condition characterized by a disconnection from reality, often manifesting as hallucinations or delusions. Evidence suggests that lifestyle factors reduce the risk of developing psychosis. A recent study found that using a sauna three or more times a week reduces the risk of psychosis by more than half, regardless of fitness levels.

    Researchers drew on data from the Kuopio Ischemic Heart Disease Risk Factor Study, an ongoing investigation of adult men living in Finland. The researchers assessed the men’s cardiorespiratory fitness and collected information about their weekly sauna use, categorized as low use (fewer than two sessions) or high use (three or more sessions). They identified participants who had been diagnosed with psychosis during a period of about 25 years.

    They found that cardiorespiratory fitness markedly reduced the risk of psychosis, with medium fitness reducing risk by 35 percent and high fitness reducing risk by 25 percent. However, they found that high sauna use reduced the risk of developing psychosis by 50 percent compared to low use, even when they took fitness levels into account.

    These findings suggest that frequent sauna use and medium to high cardiorespiratory fitness independently reduce the risk of psychosis. However, frequent sauna use might lower the risk of psychosis regardless of fitness levels and could be a stronger predictor of reduced psychosis risk than cardiorespiratory fitness.

    Sauna use exposes the body to extreme heat, stressing the body. Heat stress reduces systemic inflammation, oxidative stress, and cortisol levels, which may play roles in the development of psychosis. Learn more about the brain benefits of sauna use in this episode featuring Dr. Rhonda Patrick.

  • While brain aging is an inevitable part of growing older, lifestyle factors, particularly diet, can influence the rate at which this aging occurs. A recent study found that older adults with diets rich in omega-3 fatty acids, antioxidants, and vitamins demonstrate slower brain aging and better performance on cognitive tests.

    Researchers administered cognitive tests and brain imaging scans to 100 healthy older adults. They also measured 13 nutrition-related biomarkers in the participants' blood.

    They identified two brain aging patterns among the participants, with one group exhibiting accelerated aging and the other slower aging. Further analysis revealed that distinct dietary patterns distinguished the two groups. In particular, the intake of specific nutrients positively influenced brain health and cognitive function, including: - Alpha-linolenic acid (an omega-3 fatty acid found in nuts and seeds, such as walnuts and chia) - Eicosapentaenoic acid (an omega-3 fatty acid found in fatty fish, such as salmon) - Lutein (a polyphenol found in green leafy vegetables, such as kale) - Zeaxanthin (a polyphenol found in brightly colored vegetables, such as orange bell peppers and butternut squash) - Vitamin E (found in seeds and nuts, such as sunflower seeds and hazelnuts) - Choline (found in a variety of foods, including eggs and soybeans) These patterns were consistent even when considering the participants' demographics, fitness levels, and body measurements.

    These findings suggest that nutrient-rich diets are critical for maintaining cognitive health and decelerating the brain’s aging process. They also highlight the importance of dietary choices as potential tools to manage and mitigate age-related cognitive decline. Learn about other lifestyle choices that slow cognitive and physical aging in this episode featuring Dr. Rhonda Patrick.

  • Aggressive behaviors, such as hitting, yelling, or threatening, can cause physical or emotional harm to others. Research indicates that poor nutrition may contribute to these behaviors, suggesting that dietary interventions could be helpful strategies for reducing them. A recent review and meta-analysis found that omega-3s can reduce aggressive behaviors by as much as 28 percent in children and adults.

    Researchers analyzed the findings of 29 randomized controlled trials investigating the effects of omega-3s on behavior. The trials included more than 3,900 participants and involved children and adults of varying ages.

    Their analysis revealed that omega-3s exerted a short-term effect on behavior, with reductions ranging from 16 to 28 percent, regardless of age, gender, baseline diagnosis, treatment duration, or dose. Interestingly, omega-3s reduced reactive aggression (impulsive behavior in response to a perceived threat) and proactive aggression (premeditated to achieve a specific goal).

    These findings suggest that omega-3s positively influence behavior in children and adults and offer a potential strategy for moderating behavior problems in multiple settings, including the community, prisons, and clinics.

    Omega-3 fatty acids are essential for normal brain function, contributing to cell membrane structure, nerve growth, neurotransmitter regulation, and reducing inflammation. Learn more about omega-3s in our comprehensive overview article.

  • Physical exertion and strong emotions activate the body’s stress response, triggering the release of hormones that restrict blood flow to the body’s tissues, including the heart. A 2016 study found that these stressors increase the risk of myocardial infarction (heart attack).

    Researchers conducted a case-control study involving more than 12,000 cases of acute MI among people living in 52 countries. They asked the participants about their physical activities and emotional state in the hours before the onset of symptoms. They estimated the odds of acute MI within one hour of triggers.

    They found that 28 percent of those who experienced an acute MI had engaged in physical activity or were emotionally upset one hour before symptom onset. The likelihood of experiencing an acute MI was 2.31 times higher after physical exertion and 2.44 times higher after emotional upset. However, those who reported both physical exertion and emotional upset were 3.05 times more likely to experience an acute MI within one hour. The increased risk was consistent regardless of the participants' geographical location, sex, baseline physical activity, or age.

    These findings suggest that sudden physical exertion and emotional upset increase the risk of acute MI. However, robust evidence demonstrates that regular physical activity is crucial for preventing cardiovascular disease, including acute MI, especially among inactive people. The authors of this report recommended that clinicians continue to advocate for regular physical exercise and caution patients that intense physical activities could trigger an acute MI in those at risk.

  • Loneliness is a profound emotional and psychological state that can have far-reaching effects on mental health, especially among young people, for whom increases in depression, anxiety, self-harm, and suicidal ideation often accompany their loneliness. A recent systematic review and meta-analysis found that loneliness is more intense among young people with attention deficit hyperactivity disorder (ADHD).

    Researchers analyzed the findings of 23 studies to determine how loneliness levels differed between young people (under age 25) with or without ADHD. Then, they looked at links between loneliness and mental health problems in young people with ADHD.

    They found that young people with ADHD experience considerably higher levels of loneliness than those without. They also found a correlation between loneliness and various mental health problems among young people with ADHD.

    ADHD is a neurobehavioral condition characterized by inattention and/or hyperactive or impulsive behavior. It affects people across the lifespan and influences aspects of their academic, occupational, and social functioning.

    These findings suggest that young people with ADHD are particularly vulnerable to loneliness and the mental health problems that accompany it. Sleep deprivation can contribute to feelings of loneliness, too. Learn more in this clip featuring sleep expert Dr. Matthew Walker.

  • 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.

  • 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.

  • Many older adults have generalized anxiety disorder, a persistent feeling of anxiety or dread that interferes with everyday life. Evidence suggests that physical activity alleviates symptoms of anxiety, but scientists don’t know how much activity is optimal. A recent study found that older adults who engaged in regular physical activity were 47 percent less likely to experience symptoms of anxiety than those who engaged in no activity.

    Researchers drew on data from more than 7,600 older adults enrolled in The Irish Longitudinal Study on Ageing (TILDA). They gathered information about the participants' physical activity levels, worry symptoms, and anxiety levels over ten years. They assessed the participants' activity levels and categorized them as having no, low, medium, or high activity levels.

    They found that participants with high activity levels were 31 percent less likely to develop anxiety than those with no activity. However, participants who engaged in even minimal moderate-intensity physical activity – equivalent to just 10 minutes a day, five times a week – were 47 percent less likely to develop anxiety than those with no activity.

    These findings suggest that even a small amount of physical activity has robust effects on mood in older adults, markedly reducing the risk of developing anxiety. They also align with previous research, which found that older adults enrolled in TILDA who met WHO physical activity guidelines were 63 percent less likely to develop generalized anxiety disorder than those who did not.

    Exercise supports the health of pericytes, tiny contractile cells surrounding the brain’s capillaries that regulate vascular blood flow and maintain blood-brain barrier integrity. Pericytes detach from the blood vessels in aging, driving the pathophysiology of neurological dysfunction, vascular dementia, and mood disorders like anxiety. Learn more in this episode featuring Dr. Axel Montagne.

  • Breathing is an essential and regular process that provides the body with oxygen and removes carbon dioxide. But new research indicates that breathing influences brain function. People who breathed through their noses performed better on memory and emotional expression interpretation tests than when they breathed through their mouths.

    Researchers investigated the relationship between breathing, the brain, and thinking. First, they conducted intracranial electroencephalograms (EEGs) to assess the effects of nasal versus oral breathing in eight people. Then they administered various tests to 107 healthy young people to determine the effects of nasal versus oral breathing on memory and the ability to interpret emotional expressions.

    The intracranial EEGs revealed that when the participants breathed through their noses, their brainwaves in areas related to smell and emotions synchronized with their breathing patterns. However, breathing through their mouths diminished these effects. Similarly, when participants breathed through their noses, they performed better on memory tests. Interestingly, breathwork also influenced their ability to interpret emotional expressions. For example, their ability to interpret fear was faster during inhalation versus exhalation.

    These findings suggest that breathing, especially nasal breathing, has more complex effects on the body than previously understood. They also highlight a novel means to improve cognitive function. Learn about other effects of breathing techniques in this clip featuring Wim Hof.

  • Although vitamin D is best known for its role in bone health, this fat-soluble vitamin participates in many physiological processes, such as blood pressure regulation, immune function, and cell growth. Now, new research shows that vitamin D also supports neurodevelopment. Young children who received supplemental vitamin D were less likely to have neurobehavioral problems later in childhood than those who didn’t.

    Researchers gave 346 infants either low-dose (400 IU) or high-dose (1,200 IU) vitamin D daily from two weeks to two years of age. Then, when the children were between six and eight years old, their parents completed questionnaires regarding their children’s behavior, particularly internalizing behaviors, such as depression, anxiety, and withdrawal. They also collected information about the mothers' prenatal vitamin D status.

    They found that nearly 12 percent of the children on low-dose vitamin D exhibited internalizing behaviors between the ages of six and eight. However, fewer than 6 percent of those on the high-dose vitamin D exhibited internalizing behaviors, even after considering other factors that influence behavior, such as sex, maternal depression, and living in a single-parent household. Notably, 48 children in the low-dose group whose mothers had low prenatal vitamin D levels exhibited more internalizing behaviors than those in the high-dose group, suggesting that vitamin D supplementation in early childhood compensated for low prenatal exposure.

    These findings highlight yet another role of vitamin D in human health. Learn more about vitamin D in our overview article.

  • 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.

  • From the article:

    The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that codes for BDNF [Val66Met genotype] (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.

    The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain’s memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.

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  • 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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  • From the article:

    Misra compared 109 female athletes with exercise-induced menstrual irregularities with 50 female athletes with normal menstrual cycles and 39 female non-athletes. All of the study subjects were 14-25 years old and were in a normal weight range. The young women’s eating behavior and mental health was evaluated with self-report assessments and questionnaires.

    Athletes with irregular periods reported a higher drive for thinness and more mental control over their food intake compared with athletes with regular periods and non-athletes. They also had higher mean body dissatisfaction scores than athletes with regular periods.

    Athletes who had irregular menstrual periods were randomly assigned to receive either estrogen replacement through a patch, at a dose that resulted in estrogen levels seen with normal menstrual cycles; a commonly used combined oral contraceptive pill containing estrogen; or no estrogen for 12 months. Athletes randomized to estrogen replacement as a patch also received cyclic progesterone.

    Over one year, the groups that received estrogen showed reductions in drive for thinness, body dissatisfaction and uncontrolled eating, compared with those who didn’t receive estrogen. The patch was the most effective, leading to significant decreases in body dissatisfaction and uncontrolled eating.

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  • Estrogen may protect women against post-traumatic stress disorder (PTSD), according to findings from a 2017 study. Women are more likely to experience PTSD following a traumatic event if their estrogen levels are low.

    The study involved 239 women who had been diagnosed with PTSD. Because methylation turns on or off the activity of genes, researchers analyzed methylation patterns in the women’s DNA to see how estrogen influenced gene activity.

    They found that estrogen levels were associated with DNA methylation across the women’s genomes. In particular, estrogen influenced the activity of a gene called HDAC4, which plays important roles in memory and fear processing. Women who carried certain variants of HDAC4 exhibited an impaired ability to deal with and recover from a traumatic event. They also had stronger connections in regions of their brains involved in fear learning.

    PTSD is a neuropsychiatric disorder that may occur in people who have experienced or witnessed a traumatic event. As many as 3 million people living in the United States will be diagnosed with PTSD each year.

    These findings demonstrate that estrogen influences a woman’s risk of developing PTSD and suggest that estrogen may be useful as a therapeutic measure following exposure to a traumatic event. Some evidence suggests that psychedelic drugs may be useful in treating PTSD. Learn more in this clip featuring Dr. Roland Griffiths.

  • From the article:

    The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification of DNA that is usually a sign of genes that are turned off.

    […]

    “We knew that estrogen affects the activity of many genes throughout the genome,” […] “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”

    That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning.

    On top of that, experiments with female mice showed that the HDAC4 gene was activated in the amygdala while the mice were undergoing fear learning, but only when estrogen levels in the mice were low.

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  • 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.

  • 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.

  • 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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  • 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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  • 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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  • 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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  • 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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  • Sleep deprivation reduces testosterone levels in young men.

    Just one week of sleep deprivation reduces young men’s testosterone levels by as much as 15 percent, according to a 2011 study. Missing out on sleep worsened the young men’s mood and overall energy levels, too.

    In the study, 10 young, healthy, college-age men got a good night’s sleep for three nights, and then they got just five hours per night for eight nights. Researchers monitored their sleep and collected blood samples from the men every 15 to 30 minutes throughout the last day of each sleep protocol.

    They found that getting five hours of sleep a night for just one week drastically reduced the men’s testosterone levels – by as much as 10 to 15 percent. Testosterone levels began to plummet in the afternoons and continued to drop until late at night. The men also experienced marked reductions in their overall energy levels and moods.

    Roughly one-third of working adults in the United States get fewer than six hours of sleep every night – a problem linked with a variety of acute and chronic health conditions, including an increased risk of colds, high blood pressure, diabetes, heart attack, heart failure, and stroke. Evidence suggests that poor sleep reduces sex drive.

    The findings from this study suggest that getting even a few nights of poor sleep alters testosterone, energy levels, and mood in young, healthy men. Learn about other effects of sleep deprivation in this clip featuring Dr. Matthew Walker.

  • 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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  • From the article:

    Yale enrolled the largest number of participants at any one site (84 of 790) for these double-blind, placebo-controlled trials that investigated the efficacy of testosterone gel for multiple outcomes, including sexual function, physical function, and vitality.

    The researchers found that men who received testosterone therapy for one year, versus those on placebo, saw significant improvements in sexual function, including sexual activity, sexual desire, and erectile function.

    […]

    While participants enrolled in the trial that assessed physical function did not see significant improvements in their walking ability – as measured by an increase of 50 meters or more in their distance walked in 6 minutes – an increase was found when all study participants were evaluated. In addition, men enrolled in the vitality trial saw modest benefits in terms of improved mood and fewer depressive symptoms.

    While the results were somewhat mixed, Gill noted an overall benefit that had not been seen in previous studies. “One way of interpreting the results across trials is a global impression of change,” he said. “We found that testosterone improved men’s impression that their sexual desire, walking ability, energy level, and overall health were better.”

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  • From the article:

    “We discovered that higher levels of interleukin-6, an inflammatory marker, were associated with changes in the neonatal amygdala in terms of its anatomy and connectivity. Furthermore, our subsequent findings showed that these changes were also associated with lower impulse control at 2 years of age,” explains Prof. Buß. “We therefore conclude that a link exists between higher levels of maternal inflammatory markers and an increased risk of psychiatric disorders that are commonly associated with impaired impulse control.” Animal models have shown that infections and inflammation in the pregnant animal lead to both changes in offspring brain development and behavior. Epidemiological studies also support the findings of this study, suggesting that maternal infections and other clinical phenotypes associated with increased interleukin-6 concentrations (such as obesity) during pregnancy increase the risk of psychiatric disorders such as schizophrenia and autism.

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  • 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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  • To optimize children’s physical, social, and emotional well-being, the American Academy of Pediatrics (AAP) recommends that children eat plenty of fruits and vegetables, limit screen time, and regularly engage in physical activity. Findings from a recent study suggest that meeting the guidelines for physical activity and screen time is related to greater executive function in toddlers.

    Executive functions are defined as neurocognitive processes that influence working memory, flexible thinking, and self-control. People with lower executive functioning are more likely to exhibit low academic performance, poor physical health, financial difficulties, and substance dependence than those with higher executive function.

    The study involved 356 toddlers (24 months old) enrolled in the STRONG Kids2 study, an ongoing investigation into how individual biology interacts with the family environment to promote healthy eating habits in young children. The children’s parents completed questionnaires about their child’s diet, physical activity, and daily screen time.

    The investigators found that toddlers that met the AAP guidelines had greater executive function and self-control. They also showed greater evidence of emergent metacognition – the emerging awareness and understanding of their own thought processes, an essential component of the learning process. Toddlers who were physically active every day showed the highest levels of emergent metacognition. Taken together, these findings suggest that less screen time and more physical activity help children develop executive functioning skills.

  • 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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  • 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.

  • IL-6 may drive inflammation in neuropsychiatric disorders.

    Neuropsychiatric disorders are the leading cause of disability among people living in the United States, accounting for nearly 20 percent of all years of life lost to disability and premature death. Evidence suggests that brain inflammation is a key player in neuropsychiatric disorders, the effects of which may be bidirectional. A recent study identified potential links between inflammation and structural alterations in regions of the brain implicated in neuropsychiatric disorders.

    The brains of people with neuropsychiatric disorders exhibit a range of abnormal structural alterations, but researchers don’t fully understand what drives these abnormalities. One possible player is interleukin-6 (IL-6), a cytokine that can cross the blood-brain barrier, increasing the barrier’s permeability and promoting brain inflammation. In turn, this inflammation can impair synaptic pruning, a natural process that occurs in the brain between early childhood and adulthood and eliminates extra synapses. Inappropriate synaptic pruning is associated with some neuropsychiatric disorders, including schizophrenia and autism.

    The investigators searched for evidence of potential causality in the association between inflammatory cytokines and altered brain structure using Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Using data from more than 20,000 adults enrolled in the UK Biobank study, the researchers looked for associations between genetic variants that influence levels of interleukin-6 (IL-6, a pro-inflammatory cytokine), as well as other inflammatory factors. and changes in gray matter volume in specific areas of the brain. They also examined postmortem brain tissue to assess gene expression in the brain areas of interest.

    They found that genes that influence the production of pro-inflammatory molecules, especially IL-6, are strongly linked with brain structure in the temporal and frontal regions of the brain, areas of the brain commonly implicated in neuropsychiatric disorders. The postmortem analyses revealed that the overproduction of these pro-inflammatory genes is associated with disorders such as epilepsy, cognitive disorder, schizophrenia, psychotic disorder, and autism spectrum disorder.

    These findings suggest that pro-inflammatory pathways, especially those associated with IL-6, are essential for normal brain structural development and IL-6 elevation may drive structural alterations implicated in neuropsychiatric disorders. Evidence suggests that heat stress reduces symptoms associated with depression, a type of neuropsychiatric disorder. Learn about a clinical trial that is investigating the benefits of heat stress in this episode featuring Dr. Ashley Mason.

  • Serious neuropsychiatric disorders increase the risk of dying from cardiovascular disease.

    People who have serious neuropsychiatric disorders, such as bipolar disorder, schizophrenia, or schizoaffective disorder, are more likely to die of premature causes than their peers, often as much as 10 to 20 years earlier. Findings presented in a recent report suggest that people with serious neuropsychiatric disorders have an increased risk of dying from cardiovascular disease.

    Cardiovascular disease is a large class of diseases that involve the heart or blood vessels, including stroke, hypertension, thrombosis, heart failure, atherosclerosis, and others. A principal driver of cardiovascular disease is inflammation. Interestingly, robust evidence indicates that inflammation and neuropsychiatric disorders are also linked, and the two demonstrate a bidirectional relationship. For example, people who have depression tend to have high levels of systemic inflammation, and depression induces chronic activation of the immune system, driving inflammation.

    The authors of the report analyzed the medical records of nearly 600,000 people between the ages of 18 and 75 years. They calculated the participants' 10-year and 30-year cardiovascular disease risk using the atherosclerotic cardiovascular disease risk score for adults aged 40 to 75 years and the Framingham risk score for adults aged 18 to 59 years, respectively. They also identified participants who had been diagnosed with a serious neuropsychiatric disorder and collected participants' demographic data.

    They found that both the 10‐year and 30-year cardiovascular risk among participants with serious neuropsychiatric disorders was higher than among participants without, even after taking age, sex, race, and ethnicity into account. The primary contributors to the increased risk were higher body mass index and smoking. Participants with bipolar disorder were more likely to have higher 10-year risk; those with schizoaffective disorder were more likely to have higher 30-year risk.

    These findings suggest that having a serious neuropsychiatric disorder increases the risk of cardiovascular disease, and this risk is evident in early adulthood. Check out our overview articles to learn how lifestyle habits that reduce inflammation, such as aerobic exercise, sauna use, and cold exposure, may reduce cardiovascular disease risk and improve mental health status.

  • Roughly half of the world’s population lives in urban areas, far removed from the natural environment. Evidence indicates that people who live in urban areas are at greater risk for mental health disorders, such as depression. Findings from a new study suggest that walking in nature reduces ruminative thinking and decreases activity in parts of the brain associated with mental illness.

    Ruminative thinking – dwelling on ideas (especially stressors) to excess – is a common feature of mental illness. Rumination can set in motion a cascade of hormonal and physiological responses that harm mental and physical health. A major player in the body’s response to rumination is a biological pathway that starts in the brain’s hypothalamus with the release of corticotrophin-releasing hormone, which drives the stress hormone system and has a direct effect on many parts of the body, including the brain, gut, and DNA.

    Spending time in nature is associated with a variety of beneficial effects on mental and physical health. For example, some research indicates that walking in forested areas, sometimes referred to as “forest bathing,” improves immune function, likely due to beneficial bioactive compounds produced by trees and inhaled by walkers. Other research has identified dose-dependent improvements in health following natural experiences.

    The study involved 38 mentally healthy men and women living in a large urban area. Half of the participants took a 90-minute walk in a natural area where native plants, animals, and birds were in abundance. The other half took a 90-minute walk in an urban area where there were busy streets and heavy traffic. To rule out any physiological effects of exercise on brain health and function, both groups wore monitors to measure their heart rate and respirations. After their respective walks, participants underwent magnetic resonance imaging (MRI) studies of their brains, with emphasis on the subgenual prefrontal cortex, an area of the brain involved in emotional regulation and reward mechanisms. They also completed a questionnaire in which they rated their ruminative tendencies.

    The MRI studies revealed that after the participants walked in a natural area, their subgenual prefrontal cortex showed less activity. Those who walked in the urban area showed no changes in this region of the brain. Participants who walked in the natural area also reported less ruminative thinking after the walk, but those who walked in the urban area did not. The monitors revealed that the walks were equal in distance and exerted no physiological effects on the walkers.

    These findings suggest that spending time in the natural environment benefits brain health and reduces ruminative thinking, underscoring the importance of public health measures to increase natural spaces within urban areas. If natural areas are not easily accessible, meditation offers another means of reducing ruminative thinking. Learn more about the benefits of meditation in this episode featuring Dr. Rhonda Patrick.

  • 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.

  • “Pharmacological restoration of ASM to the normal range improves pathology in AD mice The ASM-mediated lysosomal/autophagic dysfunction in AD prompted us to examine possible therapeutic implications of this pathway. To decrease ASM in APP/PS1 mice, we undertook pharmacological inhibition using amitriptyline-hydrochloride (AMI) for 4 mo (Fig. 9 A). AMI is a known inhibitor of ASM that can cross the blood–brain barrier. At 9 mo of age, AMI-treated APP/PS1 mice exhibited decreased ASM activity compared with vehicle-treated mice (Fig. 9 B). Other sphingolipid metabolites were not changed (Fig. 9 C). Aβ levels were decreased in the AMI-treated APP/PS1 mice compared with the nontreated littermates.”

    “ASM activity is known to be increased by environmental stress and in various diseases, and is elevated in AD patients (He and Schuchman, 2012). One downstream consequence of increased ASM is elevated ceramide, contributing to cell death, inflammation, and other common disease findings. Although elevated ASM is known to occur in AD, the cellular mechanisms that link ASM and AD have not been fully characterized. The data presented here suggest a previously unknown role of ASM in the down-regulation of lysosomal biogenesis and inhibition of lysosome-dependent autophagic proteolysis. The findings also establish proof of concept for ASM inhibitor therapy in AD.”

  • 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.