Schizophrenia
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Dr. Rhonda Patrick makes her fifth appearance on the Joe Rogan Experience.
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Nutrition Vitamin D Metabolism Diabetes Telomeres Omega-3 Inflammation Depression DNA Damage Stem Cells Micronutrients Mitochondria Autophagy Autism Schizophrenia Resveratrol Sulforaphane Insulin Blue LightDr. Rhonda Patrick makes her fifth appearance on the Joe Rogan Experience.
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Vitamin D shapes neurodevelopment, influencing the development of dopamine-producing neurons and, ultimately, the risk of schizophrenia. onlinelibrary.wiley.com
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.
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Maternal vitamin D deficiency linked to potential developmental disorders, emphasizing a role in dopamine signaling. neurosciencenews.com
Dopamine is a neurotransmitter best known for its role in motor, motivation, and pleasure control. A new study highlights vitamin D’s influence on dopamine signaling and emphasizes its essential role in the normal development of dopamine-producing cells.
Researchers developed three cell lines to mimic the natural process of embryonic development, during which cells differentiate (specialize) into dopamine-producing neurons. Then they cultured the cells in the presence or absence of vitamin D.
They found that vitamin D participated in neuronal growth and branching, the rearrangement of presynaptic proteins, and the production and release of dopamine. The researchers posited that glial-derived growth factor, a vitamin D-dependent factor that promotes dopamine neuron differentiation, was the mechanism driving these effects.
These findings suggest that vitamin D plays multiple roles in dopamine signaling, with potential implications for neurodevelopmental disorders like schizophrenia, ADHD, and autism. They also underscore the importance of adequate maternal vitamin D status during pregnancy.
Interestingly, vitamin D and omega-3 fatty acids may synergistically work to support neurodevelopment further. Read this open-access peer-reviewed article by Dr. Rhonda Patrick to learn more.
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Estrogen fluctuations may trigger atypical hippocampal working memory function in women with a BDNF genotype present in one in four women. (2017) www.sciencedaily.com
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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Infection-induced interleukin-6 secretion in mice increases the risk for schizophrenia- and autism-like behaviors in offspring. (2007) www.sciencedaily.com
From the article:
It has been known for some time that schizophrenia is more common among people born in the winter and spring months, as well as in people born following influenza epidemics. Recent studies suggest that if a woman suffers even one respiratory infection during her second trimester, her offspring’s risk of schizophrenia rises by three to seven times.
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To prove this, they triggered an artificial immune response in pregnant mice–giving them a faux case of the flu. The trigger they used was a snippet of double-stranded RNA called poly(I:C), which fools the immune system into thinking there has been an infection by an RNA virus.
A single, mid-gestation injection of poly(I:C) creates a strong immune response in a pregnant mouse. When her offspring reach adulthood, they display behavioral and tissue abnormalities similar to those seen in schizophrenia in humans.
Though there might be some disagreement over what it means for a mouse to be schizophrenic, these abnormalities are generally marked by inappropriateness of response and difficulty in coping.
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The team tried injecting the pregnant mice with individual cytokines, rather than with poly(I:C). It turned out that after a single dose of a specific cytokine known as interleukin-6 (or IL-6), a mouse would give birth to offspring who, at maturity, exhibited the familiar schizophrenia- and autism-like behaviors.
To confirm the role of IL-6, Steve Smith, the lead researcher, gave fake colds (poly(I:C)) to two groups of pregnant, IL-6-free mice. One group had received anti-IL-6 antibodies which blocked IL-6; the other consisted of so-called IL-6 knockout mice (mice whose genetic makeup prevents them from synthesizing IL-6). In both groups, offspring grew up normal, showing that IL-6 is necessary for the maternal poly(I:C) treatment to alter fetal brain development and subsequent behavior in the offspring.
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Maternal immune activation during pregnancy is associated with changes in the newborns' stimulus processing and long-term development. (2018) www.sciencedaily.com
From the article:
Blood drawn from mothers during their third trimester was tested for levels of IL-6 and CRP – two proteins that are found at higher levels when the immune system is activated. Peterson’s team also monitored fetal heart rate as an indicator for nervous system development. The team found that CRP did correlate with variability of the fetal heart rate, which is influenced heavily by the nervous system, indicating that maternal inflammation was already beginning to shape brain development.
When the babies were born, they were given MRI scans in their first few weeks of life, providing researchers a unique view of early neural development and the influence of prenatal factors. Brain imaging revealed a striking finding – significant changes in the communication between specific brain regions correlated with elevated maternal IL-6 and CRP levels. These brain regions are known collectively as the salience network, whose job is to filter stimuli coming into the brain and determine which deserve attention.
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“The salience network sifts through that information and decides what is important and warrants action.” Disturbances in the functioning of this network, as well as various kind of infection and other triggers of a pregnant woman’s immune response, have been linked to development of psychiatric illnesses, such as schizophrenia and autism spectrum disorders.
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The correlations of elevated maternal inflammatory markers were not limited to the newborn period, but continued to persist into toddlerhood. When the babies turned 14 months of age, researchers assessed them for motor skills, language development, and behavior. Following the established Bayley Scales of Infant and Toddler Development-Third Edition, Peterson found significant changes in the scores of toddlers born to mothers with elevated levels of both IL-6 and CRP.
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Higher maternal interleukin-6 (IL-6) levels are associated with changes in the newborn amygdala leading to altered impulse control. (2017) www.sciencedaily.com
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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Blockade of IL-6 receptor improved cognition in patients with schizophrenia. (2016) www.sciencedaily.com
From the article:
After just two intravenous doses in eight weeks of tocilizumab, an immune-suppressing drug regularly prescribed for rheumatoid and juvenile arthritis, study participants had significantly improved cognitive ability, said Dr. Brian J. Miller, a psychiatrist at the Medical College of Georgia at Augusta University.
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Anywhere from 25 to 50 percent of patients may have inflammation in the brain contributing to that dysfunction. Problems range from having trouble remembering important numbers to impairment of executive function that enables them to analyze, organize, and generally manage their lives.
Tocilizumab targets the receptor for IL-6, a protein which helps regulate inflammation that is often elevated in patients with schizophrenia. Higher IL-6 levels also have been correlated with a smaller hippocampus, a center for learning and memory in the brain, as well as experiencing more psychiatric symptoms.
The five study patients did not experience improvement in overall levels of psychiatric symptoms, such as hallucinations and delusions, more classic symptoms of schizophrenia, which were already well-controlled with antipsychotics, Miller said.
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Sulforaphane from broccoli sprouts increase glutathione in the brain by an average of 30% with a 100 micromole per day dose www.sciencedaily.com
Increases of glutathione reverse pattern of brain cell activity associated with schizophrenia:
They used the chemical sulforaphane found in broccoli sprouts, which is known to turn on a gene that makes more of the enzyme that sticks glutamate with another molecule to make glutathione. When they treated rat brain cells with glutathione, it slowed the speed at which the nerve cells fired, meaning they were sending fewer messages. The researchers say this pushed the brain cells to behave less like the pattern found in brains with schizophrenia.
However, the impact of sulforaphane may be broader due to the broader effect of increasing glutathione, including in the hippocampus (region impacted by Alzheimer’s disease):
For their study, published in April 2018 in Molecular Neuropsychiatry, the researchers recruited nine healthy volunteers (four women, five men) to take two capsules with 100 micromoles [17.729mg] daily of sulforaphane in the form of broccoli sprout extract for seven days.
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The researchers used MRS again to monitor three brain regions for glutathione levels in the healthy volunteers before and after taking sulforaphane. They found that after seven days, there was about a 30% increase in average glutathione levels in the subjects' brains. For example, in the hippocampus, glutathione levels rose an average of 0.27 millimolar from a baseline of 1.1 millimolar after seven days of taking sulforaphane.
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Abnormal striatal function may be a promising biomarker for diagnosis and evaluating treatment efficacy in schizophrenia www.eurekalert.org
The researchers showed, for the first time, that striatal dysfunction was effective in distinguishing schizophrenia patients and that such dysfunction was also responsible for poorer antipsychotic response. This may be an important tool for objectively diagnosing and treatment response rather than the current approach, which primarily relies on the “softer” endpoint of patient behavior.
From the article:
The researchers showed, for the first time, that striatal dysfunction was effective in distinguishing schizophrenia patients and that such dysfunction was also responsible for poorer antipsychotic response.
Based on the newly developed biomarker, the researchers extended their research to other neuropsychiatric disorders. They showed that individuals with bipolar disorder also showed striatal dysfunction that overlapped with the dysfunction associated with schizophrenia.
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A new study proposes exercise as a potential primary mode of treatment for mental health disorders. www.sciencedaily.com
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.