Posts Tagged serotonin
In general, the term ‘fatigue’ is used to describe any exercise-induced decline in the ability of a muscle to generate force. To identify the causes of fatigue, it is common to examine two divisions of the body that might be affected during exercise. The central component of fatigue includes the many nerves that travel throughout the brain to the spinal cord. The peripheral component predominantly reflects elements in the muscle itself. If there is a problem with either of these components, the ability to contract a muscle might be compromised. For many years, there has been suggestion that central fatigue is heavily influenced by neurotransmitters that get released in the central nervous system (such as dopamine and serotonin). However, little research has been performed in this area.
Serotonin is a chemical that can improve mood, and increasing the amount of serotonin that circulates in the brain is a common therapy for depression. However, serotonin also plays a vital role in activating neurons in the spinal cord which tell the muscle to contract. With the correct amount of serotonin release, a muscle will activate efficiently. However, if too much serotonin is released, there is a possibility that the muscle will rapidly fatigue. Recent animal studies indicate that moderate amounts of serotonin release, which are common during exercise, can promote muscle contractions (Cotel et al. 2013). However, massive serotonin release, which may occur with very large bouts of exercise, could further exacerbate the already fatigued muscle (Perrier et al. 2018).
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. These medications keep serotonin levels high in the central nervous system by stopping the chemical from being reabsorbed by nerves (reuptake inhibition). Instead of using SSRIs to relieve symptoms of depression, we used them in our recent study (Kavanagh et al. 2019) to elevate serotonin in the central nervous system, and then determine if characteristics of fatigue are enhanced when serotonin is elevated. We performed three experiments that used maximal voluntary contractions of the biceps muscle to cause fatigue in healthy young individuals. Our main goal was to determine if excessive serotonin limits the amount of exercise that can be performed, and then determine which central or peripheral component was compromised by excessive serotonin.
WHAT DID WE FIND?
Given that SSRIs influence neurotransmitters in the central nervous system, it was not surprising that peripheral fatigue was unaltered by the medication. However, central fatigue was influenced with enhanced serotonin. The time that a maximum voluntary contraction could be held was reduced with enhanced serotonin, whereby the ability of the central nervous system to drive the muscle was compromised by 2-5%. We further explored the location of dysfunction and found that the neurons in the spinal cord that activate the muscle were 4-18% less excitable when fatiguing contractions were performed in the presence of enhanced serotonin.
SIGNIFICANCE AND IMPLICATIONS
The central nervous system is diverse, and the fatigue that is experienced during exercise is not just restricted to the brain. Instead, the spinal cord plays an integral role in activating muscles, and mechanisms of fatigue also occur in these lower, often overlooked, neural circuits. This is the first study to provide evidence that serotonin released onto the motoneurones contributes to central fatigue in humans.
Kavanagh JJ, McFarland AJ, Taylor JL. Enhanced availability of serotonin increases activation of unfatigued muscle but exacerbates central fatigue during prolonged sustained contractions. J Physiol. 597:319-332, 2019.
If you cannot access the paper, please click here to request a copy.
Cotel F, Exley R, Cragg SJ, Perrier JF. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation. Proc Natl Acad Sci U S A. 110:4774-4779, 2013.
Perrier JF, Rasmussen HB, Jørgensen LK, Berg RW. Intense activity of the raphe spinal pathway depresses motor activity via a serotonin dependent mechanism. Front Neural Circuits. 11:111, 2018.
Associate Professor Justin Kavanagh is a researcher and lecturer at Griffith University. His team explores how the central nervous system controls voluntary and involuntary movement, and he has particular interests in understanding how medications can be used to study mechanisms of human movement.
Dopamine is a chemical found naturally in the human body. It is a neurotransmitter, meaning it sends signals from the body to the brain.
Dopamine plays a part in controlling the movements a person makes, as well as their emotional responses. The right balance of dopamine is vital for both physical and mental wellbeing.
Vital brain functions that affect mood, sleep, memory, learning, concentration, and motor control are influenced by the levels of dopamine in a person’s body. A dopamine deficiency may be related to certain medical conditions, including depression and Parkinson’s disease.
A dopamine deficiency can be due to a drop in the amount of dopamine made by the body or a problem with the receptors in the brain.
The symptoms of a dopamine deficiency depend on the underlying cause. For example, a person with Parkinson’s disease will experience very different symptoms from someone with low dopamine levels due to drug use.
Some signs and symptoms of conditions related to a dopamine deficiency include:
- muscle cramps, spasms, or tremors
- aches and pains
- stiffness in the muscles
- loss of balance
- difficulty eating and swallowing
- weight loss or weight gain
- gastroesophageal reflux disease (GERD)
- frequent pneumonia
- trouble sleeping or disturbed sleep
- low energy
- an inability to focus
- moving or speaking more slowly than usual
- feeling fatigued
- feeling demotivated
- feeling inexplicably sad or tearful
- mood swings
- feeling hopeless
- having low self-esteem
- feeling guilt-ridden
- feeling anxious
- suicidal thoughts or thoughts of self-harm
- low sex drive
- lack of insight or self-awareness
Low dopamine is linked to numerous mental health disorders but does not directly cause these conditions.
The most common conditions linked to a dopamine deficiency include:
In Parkinson’s disease, there is a loss of the nerve cells in a specific part of the brain and loss of dopamine in the same area.
It is also thought that drug abuse can affect dopamine levels. Studies have shown that repeated drug use could alter the thresholds required for dopamine cell activation and signaling.
Damage caused by drug abuse means these thresholds are higher and therefore it is more difficult for a person to experience the positive effects of dopamine. Drug abusers have also been shown to have significant decreases in dopamine D2 receptors and dopamine release.
Diets high in sugar and saturated fats can suppress dopamine, and a lack of protein in a person’s diet could mean they do not have enough l-tyrosine, which is an amino acid that helps to build dopamine in the body.
Some studies have found that people who are obese are more likely to be dopamine deficient too.
There is no reliable way to measure levels of dopamine in a person. However, a doctor may look at a person’s symptoms, lifestyle factors, and medical history to determine if they have a condition related to low levels of dopamine.
If a person is diagnosed with a mental health condition, such as depression or schizophrenia, a doctor may prescribe medications to help with the symptoms. These drugs may include anti-depressants and mood stabilizers.
Ropinirole and pramipexole can boost dopamine levels and are often prescribed to treat Parkinson’s disease. Levodopa is usually prescribed when Parkinson’s is first diagnosed.
Other treatments for a dopamine deficiency may include:
- changes in diet and lifestyle
- physical therapy for muscle stiffness and movement problems
Activities that make a person feel happy and relaxed are also thought to increase dopamine levels. These may include exercise, therapeutic massage, and meditation.
Dopamine vs. serotonin
Dopamine and serotonin are both naturally occurring chemicals in the body that have roles in a person’s mood and wellbeing.
Serotonin influences a person’s mood and emotions, as well as sleep patterns, appetite, body temperature, and hormonal activity, such as the menstrual cycle.
Some researchers believe that low levels of serotonin contribute to depression. The relationship between serotonin and depression and other mood disorders is complex and unlikely to be caused by a serotonin imbalance alone.
Additionally, dopamine affects how a person’s moves, but there is no clear link to the role of serotonin in movement.
Dopamine deficiency can have a significant impact on a person’s quality of life, affecting them both physically and mentally. Many mental health disorders are linked to low levels of dopamine. Other medical conditions, including Parkinson’s disease, have also been linked to low dopamine.
There is limited evidence that diet and lifestyle can affect the levels of dopamine a person creates and transmits in their body. Certain medications and some therapies may help relieve symptoms, but a person should always speak to a doctor first if they are concerned about their dopamine levels.
Deficiency of monoamines, such as dopamine, epinephrine, and serotonin, is the most widely accepted theory explaining mood disorders. Among these neuromediators, serotonin deficiency is considered as most significant in relation to anxiety and depression. This theory has been proven by the effectiveness of drugs that help to increase monoamines levels in the brain, although research in this direction has been hampered by the limitations of present-day technology in measuring the levels of specific monoamines and their properties. However, studies do indicate that their deficiency plays a role in individuals prone to mood swings.
Tryptophan as precursor for serotonin
Tryptophan is one of the essential amino acids. It can’t be produced by our body and has to come through food products rich in proteins. It is required for both anabolic processes and production of various hormones. Tryptophan is a chemical precursor for the synthesis of the neurotransmitter serotonin. This means that the amount of serotonin produced in our body is dependent on the dietary intake of tryptophan. Since serotonin is related to mood regulation, it is entirely possible that tryptophan deficits may have a negative effect on our mood state. On the other hand, its supplementation may be helpful in disorders like anxiety or depression. Multiple investigations seem to support the idea that decreased levels of tryptophan lead to a reduction in serotonin and changes in mood. Some studies have indicated that higher intake of tryptophan may improve social interactions by improving mood and decreasing aggression and dominant behavior.
Serotonin in mood and cognition
Serotonin is important for both mood regulation and regulation of cognitive functions like learning and memory. The effect of monoamine inhibitors called serotonin reuptake inhibitors in various disorders of mood supports this theory. However, it is important to keep in mind that antidepressants are only partially effective in treating mood disorders since monoamine deficits are just one of the factors influencing mood. Most of the serotonin in our body is produced outside the brain, indicating that this compound has a much broader role in our normal physiology. It is possible that many functions of serotonin are still not understood.
Tryptophan depletion and mood regulation
To understand the role of serotonin, and more specifically tryptophan, many tryptophan-depletion studies have been done in recent times. In one simple crossover study, 25 healthy adults were studied for mood changes like anxiety and depression after consuming either a high tryptophan diet or a low tryptophan diet for four days. Tryptophan consumption seems to affect mood even in such a short interval. The study showed that those on a high tryptophan diet had much better mood as compared to those on a low tryptophan diet, although the negative effects of a low tryptophan diet were less pronounced. If such a quick and straightforward analysis can show the difference, it is entirely possible that long-term low tryptophan consumption or depletion may have much graver consequences for mental health.
Tryptophan and gut-brain axis
When we talk about the gut-brain axis we are not just discussing the digestive role of the gut and its effect on overall health, something that has been well known for many years. Our digestive system is also involved in neuro-hormonal signaling, through which it can have an impact on brain functioning. Recently, the influence of gut health on the brain has been the subject of many studies and for good reason. Our gut has more nerve cells than our spine, and it produces many hormones that have various implications for health. Further, it is now well understood that the neural relationship between the gut and brain is dual-sided, and there are more nerve fibers sending information from the gut to the brain rather than from the brain to the gut. Thus, due to the effect of nerves, hormones, and other neurologically active compounds, the gut plays a prominent role in mental wellbeing. Even small changes in the gut could directly affect our behavior. Gut microbiota and their relationship to mood have also recently received lots of attention.
When it comes to tryptophan, the digestive system is not solely involved in its absorption or metabolism. Now it is well-established that serotonin is mostly produced in the gut rather than in the brain, further strengthening the theory of gut-brain interrelation. This theory explains the mood alterations in irritable bowel syndrome (IBS). Further, the development of IBS has been shown to be connected to tryptophan depletion.
The studies show that tryptophan depletion, due to its relationship with serotonin, is undoubtedly one of the most essential elements to consider when analyzing altered mood and cognition. Low serotonin could generally cause a state of lowered mood, impaired cognition, poor working memory, and lower reasoning. Conversely, high tryptophan supplementation could have a positive effect on mood, memory, energy level, and emotional processing.
Low dietary consumption of tryptophan could be one of the elements leading to chronic conditions like depression and anxiety. Bowel conditions like IBS that disturb tryptophan metabolism and alter serotonin levels may also modify our behavior and feelings.
The search for effective therapeutic approaches to the treatment of mood disorders, anxiety, and depression has gained lots of attention in the last few decades. Understanding the role of tryptophan may open up new possibilities for managing mood and cognition problems. It is quite possible that a high tryptophan diet may not only help to prevent mood disorders but also increase the effectiveness of existing drug therapies.
Delgado, P. L. (2000) Depression: the case for a monoamine deficiency. The Journal of Clinical Psychiatry, 61 Suppl 6, 7–11. PMID: 10775018
Jenkins, T. A., Nguyen, J. C. D., Polglaze, K. E., & Bertrand, P. P. (2016) Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8(1). doi: 10.3390/nu8010056
Lindseth, G., Helland, B., & Caspers, J. (2015). The Effects of Dietary Tryptophan on Affective Disorders. Archives of Psychiatric Nursing, 29(2), 102–107. doi: 10.1016/j.apnu.2014.11.008
Young, S. N., & Leyton, M. (2002) The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels. Pharmacology, Biochemistry, and Behavior, 71(4), 857–865. PMID: 11888576
Young, S. N., Smith, S. E., Pihl, R. O., & Ervin, F. R. (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology, 87(2), 173–177. doi: 10.1007/BF00431803
Depression is characterized by persistent low mood and feelings of hopelessness, and it is one of the most common mental disorders in the United States. In 2014, there were an estimated 15.7 million U.S. adults who experienced at least one major depressive episode, representing around 6.7 percent of the country’s adults.
Treatments for depression generally include talking therapies in conjunction with medication. The class of drugs most commonly prescribed is selective serotonin reuptake inhibitors (SSRIs), and these include brands such as Prozac and Zoloft.
SSRIs can help some people with depression, but they are not perfect; not everyone responds well to them, and side effects including nausea, insomnia, agitation, and erectile dysfunction can be unpleasant.
Also, SSRIs can take some time to kick in; although some people might feel some benefit within hours or even minutes, most people do not feel the full antidepressant effect until they have been taking the drugs for weeks or even months.
How do SSRIs work?
In the brain, messages are sent between neurons by releasing neurotransmitters into a gap between the cells, or the synapse. Serotonin is one such neurotransmitter. It is released from the first neuron and binds to receptors on the second neuron.
Normally, once serotonin has been released into the synapse and relayed its message, the majority is reabsorbed into the first nerve cell for reuse at a later date. SSRIs prevent serotonin from being reabsorbed. In this way, they ensure that serotonin hangs around in the synapse for a longer time, exerting more of an effect.
Although SSRIs have been known to medical science since the 1950s, their exact mechanism is not understood. This is because there are at least 1,000 types of neuron that can be influenced by a surge in serotonin, and some of these neurons may be excited, while others might be inhibited.
The mixed response is because there are 14 subtypes of serotonin receptor throughout the body and any single nerve could have a cocktail of receptor types. Teasing out which receptor subtype is playing the most significant role has proven challenging.
The role of the dentate gyrus
A group of scientists from Rockefeller University in New York City, NY, recently set out to take a closer look at the action of SSRIs on a particular type of nerve cell. The team was headed up by Lucian Medrihan and Yotam Sagi, both research associates in the Laboratory of Molecular and Cellular Neuroscience, and Paul Greengard, Nobel laureate.
Their findings were recently published in the journal Neuron.
“Many different types of synapses throughout the brain use serotonin as their neurotransmitter. An issue of major importance has been to identify where in the myriad of neurons the antidepressants initiate their pharmacological action.”
The team concentrated on a group of cells in the dentate gyrus (DG). According to the authors, they chose the DG because previous work has established that “SSRI treatment promotes a variety of synaptic, cellular, and network adaptations in the DG.”
Specifically, the team investigated cholecystokinin (CCK)-expressing neurons within the DG. These neurons were of interest because they are heavily influenced by neurotransmitter systems that are associated with mood disorders, such as depression.
Finding the right receptor
Using a technique called translating ribosome affinity purification, the team were able to identify the serotonin receptors on CCK cells. Sage explains, “We were able to show that one type of receptor, called 5-HT2A, is important for SSRIs’ long-term effect, while the other, 5-HT1B, mediates the initiation of their effect.
The next step in the study involved efforts to mimic SSRIs’ effects by manipulating CCK neurons in mice. They used chemogenetics to switch nerve cells on or off and implanted tiny electrodes inside the mouse brains.
The findings were clear. When the CCK neurons were inhibited, the pathways important for the mediation of SSRI responses lit up. In other words, the scientists had recreated a Prozac-like effect without using the drug.
To back up these findings, the team used behavioral experiments in a pool and observed swimming patterns. Again, silencing the CCK neurons created behavior that was similar to that displayed by the mice that had been given SSRIs: they swam for longer with increased vigor.
According to the researchers, understanding the importance of the DG and the specific cells important for treating depression will help to design faster-acting, more effective antidepressants with fewer side effects.
The work was carried out using techniques that would have been impossible just 5 years ago, and the studies that follow are likely to improve our understanding even further.
[ARTICLE] Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence – Full Text HTML
Background: Several clinical studies have indicated that selective serotonin reuptake inhibitors (SSRIs) administered in patients after acute ischemic stroke can improve clinical recovery independently of depression. Due to small sample sizes and heterogeneous study designs interpretability was limited in these studies. The mechanisms of action whereby SSRI might improve recovery from acute ischemic stroke are not fully elucidated.
Methods: We searched MEDLINE using the PubMed interface to identify evidence of SSRI mediated improvement of recovery from acute ischemic stroke and reviewed the literature on the potential underlying mechanisms of action.
Results: Among identified clinical studies, a well-designed randomized, double-blind, and placebo-controlled study (FLAME – fluoxetine for motor recovery after acute ischemic stroke) demonstrated improved recovery of motor function in stroke patients receiving fluoxetine. The positive effects of SSRIs on stroke recovery were further supported by a meta-analysis of 52 trials in a total of 4060 participants published by the Cochrane collaboration. Based on animal models, the mechanisms whereby SSRIs might ameliorate functional and structural ischemic-brain damage were suggested to include stimulation of neurogenesis with migration of newly generated cells toward ischemic-brain regions, anti-inflammatory neuroprotection, improved regulation of cerebral blood flow, and modulation of the adrenergic neurohormonal system. However, to date, it remains speculative if and to what degree these mechanisms convert into humans and randomized controlled trials in large populations of stroke patients comparing different SSRIs are still lacking.
Conclusion: In addition to the need of comprehensive-clinical evidence, further elucidation of the beneficial mechanisms whereby SSRIs may improve structural and functional recovery from ischemic-brain damage is needed to form a basis for translation into clinical practice.
Continue —> Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence – Siepmann – 2015 – Brain and Behavior – Wiley Online Library
Current antidepressants take around 3 to 8 weeks to kick in and only help around 50% of people who are depressed.
A new type of antidepressant holds the promise of treating depression quickly, without too many side-effects. Professor Scott Thompson, of the University of Maryland School of Medicine who led the research, said:
“Our results open up a whole new class of potential antidepressant medications.
We have evidence that these compounds can relieve the devastating symptoms of depression in less than one day, and can do so in a way that limits some of the key disadvantages of current approaches.”
Currently used antidepressants, such as Prozac and Lexapro, target levels of the neurotransmitter serotonin.
Unfortunately they are only effective in around half of people with depression. Even amongst people they do help, it can take three to eight weeks for the effects can be felt. For patients who are suicidal, this period can be excruciating.
Also, many now believe that targeting serotonin is not effective (see: Long-Held Belief About Depression Challenged by New Study).
The new compounds focus on another neurotransmitter with the acronym GABA (gamma-aminobutyric acid), instead of serotonin. GABA mainly reduces brain activity in certain key areas related to mood.
The new class of compounds dampen down these inhibitory signals. Theoretically, the result should be to lift mood.
Professor Thompson explained that preliminary tests on animals have been encouraging:
“These compounds produced the most dramatic effects in animal studies that we could have hoped for.
It will now be tremendously exciting to find out whether they produce similar effects in depressed patients.
If these compounds can quickly provide relief of the symptoms of human depression, such as suicidal thinking, it could revolutionize the way patients are treated.”
The study found that the compounds only affected the brains of stressed rats and left unstressed rats unchanged. This may mean that the side-effects of the treatment will be less severe than those seen for current antidepressants.
The study was published in the journal Neuropsychopharmacology (Fischell et al., 2015).
A study is challenging the relationship between depression and an imbalance of serotonin levels in the brain, and brings into doubt how depression has been treated in the U.S. over the past 20 years.
Researchers at the John D. Dingell VA Medical Center and Wayne State University School of Medicine in Detroit have bred mice who cannot produce serotonin in their brains, which should theoretically make them chronically depressed. But researchers instead found that the mice showed no signs of depression, but instead acted aggressively and exhibited compulsive personality traits.
This study backs recent research indicating that selective serotonin reuptake inhibitors, or SSRIs, may not be effective in lifting people out of depression. These commonly used antidepressants such as Prozac, Paxil, Celexa, Zoloft, and Lexapro, are taken by some 10% of the U.S. population and nearly 25% of women between 40 and 60 years of age. More than 350 million people suffer from depression, according to the World Health Organization, and it is the leading cause of disability across the globe.
The study was published in the journal ACS Chemical Neuroscience. Donald Kuhn, the lead author of the study, set out to find what role, if any, serotonin played in depression. To do this, Kuhn and his associates bred mice who lacked the ability to produce serotonin in their brains, and ran a battery of behavioral tests on them. In addition to being compulsive and extremely aggressive, the mice who could not produce serotonin showed no signs of depression-like symptoms. The researchers also found, to their surprise, that under stressful conditions, the serotonin-deficient mice behaved normally.
A subset of the mice who couldn’t produce serotonin were given antidepressant medications and they responded in a similar manner to the drugs as did normal mice. Altogether, the study found that serotonin is not a major player in depression, and science should look elsewhere to identify other factors that might be involved. These results could greatly reshape depression research, the authors say, and shift the focus of the search for depression treatments.
The study joins others in directly challenging the notion that depression is related to lower levels of serotonin in the brain. One study has shown that some two-thirds of those who take SSRIs remain depressed, while another study has even found them clinically insignificant.
Critics of common antidepressants claim they’re not much better than a placebo, yet may still have unwanted side effects.
SSRIs started to become widely used in the 1980s. Their introduction was heralded by the psychiatric community as a new era where safer drugs that directly targeted the causes of depression would become the standard. While SSRIs aren’t more effective than the older antidepressants, such as tricyclics and monoamine oxidase inhibitors, they are less toxic.
An earlier study by the National Institute of Mental Health found that two out of three patients with depression don’t fully recover using modern antidepressants.
These results “are important because previously it was unclear just how effective (or ineffective) antidepressant medications are in patients seeking treatment in real-world settings,” said James Murrough, a research fellow at the Mount Sinai School of Medicine Mood and Anxiety Disorders Program.
The concept that depression is a result of low brain serotonin levels and, therefore, that selective serotonin reuptake inhibitors (SSRIs) are an effective treatment for the disorder is a myth, says a UK psychiatrist.
Moreover, David Healy, MD, professor of psychiatry, Hergest Unit, Bangor, Wales, United Kingdom, believes that SSRIs were a treatment looking for a condition and that doctors and patients were co-opted into the myth by clever marketing, resulting in better treatments being sidelined.
“This history raises a question about the weight doctors and others put on biological and epidemiological plausibility. Does a plausible (but mythical) account of biology and treatment let everyone put aside clinical trial data that show no evidence of lives saved or restored function?,” Dr Healy asks.
“In other areas of life the products we use, from computers to microwaves, improve year on year, but this is not the case for medicines, where this year’s treatments may achieve blockbuster sales despite being less effective and less safe than yesterday’s models,” he adds.
The editorial was published online April 21 in the BMJ.
Doctors, Patients Co-opted
Outlining the history of SSRIs, Dr Healy says that in the 1960s, the notion that serotonin levels are lower in persons with depression was rejected, and SSRIs were shown to be less effective than tricyclic antidepressants. The SSRIs were then marketed as tranquilizers, for which they were equally unsuccessful.
Continue —> Low Serotonin, Depression Link a Myth?.
[WEB SITE] Omega-3 Fatty Acids and Vitamin D May Control Brain Serotonin, Affecting Behavior and Psychiatric Disorders
Although essential marine omega-3 fatty acids and vitamin D have been shown to improve cognitive function and behavior in the context of certain brain disorders, the underlying mechanism has been unclear.
In a new paper published in FASEB Journal* by Rhonda Patrick, PhD and Bruce Ames, PhD of Children’s Hospital Oakland Research Institute (CHORI), serotonin is explained as the possible missing link tying together why vitamin D and marine omega-3 fatty acids might ameliorate the symptoms associated with a broad array of brain disorders.
In a previous paper published last year, authors Patrick and Ames discussed the implications of their finding that vitamin D regulates the conversion of the essential amino acid tryptophan into serotonin, and how this may influence the development of autism, particularly in developing children with poor vitamin D status.
Here they discuss the relevance of these micronutrients for neuropsychiatric illness. Serotonin affects a wide-range of cognitive functions and behaviors including mood, decision-making, social behavior, impulsive behavior, and even plays a role in social decision-making by keeping in check aggressive social responses or impulsive behavior.
Many clinical disorders, such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and depression share as a unifying attribute low brain serotonin. “In this paper we explain how serotonin is a critical modulator of executive function, impulse control, sensory gating, and pro-social behavior,” says Dr. Patrick. “We link serotonin production and function to vitamin D and omega-3 fatty acids, suggesting one way these important micronutrients help the brain function and affect the way we behave.”
Eicosapentaenoic acid (EPA) increases serotonin release from presynaptic neurons by reducing inflammatory signaling molecules in the brain known as E2 series prostaglandins, which inhibit serotonin release and suggests how inflammation may negatively impact serotonin in the brain. EPA, however, is not the only omega-3 that plays a role in the serotonin pathway. Docosahexaenoic acid (DHA) also influences the action of various serotonin receptors by making them more accessible to serotonin by increasing cell membrane fluidity in postsynaptic neurons.
Their paper illuminates the mechanistic links that explain why low vitamin D, which is mostly produced by the skin when exposed to sun, and marine omega-3 deficiencies interacts with genetic pathways, such as the serotonin pathway, that are important for brain development, social cognition, and decision-making, and how these gene-micronutrient interactions may influence neuropsychiatric outcomes. “Vitamin D, which is converted to a steroid hormone that controls about 1,000 genes, many in the brain, is a major deficiency in the US and omega-3 fatty acid deficiencies are very common because people don’t eat enough fish,” said Dr. Ames.
This publication suggests that optimizing intakes of vitamin D, EPA, and DHA would optimize brain serotonin concentrations and function, possibly preventing and ameliorating some of the symptoms associated with these disorders without side effects