- What Is Serotonin?
- A Happy Chemical: Serotonin and Mood
- The Role of Serotonin in Brain Function
- Gut Bacteria and Serotonin Production
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- How Do SSRI Drugs Work?
- Who Benefits From Use of SSRIs?
- Serotonin Foods and Supplements
- Serotonin Syndrome
- How to boost serotonin and improve mood
- Serotonin and Serotonin Deficiency
- Scroll down for 5 tips on how to increase serotonin.
- Does serotonin have any side effects?
- Know your serotonin: An interview with gut-brain axis researcher Elaine Hsiao
- Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota
- Frequently Asked Questions about Serotonin
- Microbes Help Produce Serotonin in Gut
- Serotonin’s link to autism, explained
- Serotonin Molecule
- Chemical and Physical Properties of Serotonin
What Is Serotonin?
Serotonin plays a role in many mental illnesses — and the drugs that are used to treat them.
A neurotransmitter, serotonin is known for the role it plays in feelings of well-being and happiness.
Serotonin is a hormone and a neurotransmitter that is involved in the function of several different organ systems in the body.
A Happy Chemical: Serotonin and Mood
Serotonin is sometimes known as the happy chemical, because it appears to play an important role in regulating mood, and low levels of serotonin in the brain have been associated with depression. (1)
While there’s a link between low levels of serotonin and depression, it’s not clear whether low serotonin levels cause depression or whether depression causes a drop in serotonin levels. (1)
As a neurotransmitter, serotonin sends messages between nerve cells in the brain. That makes serotonin an important molecule for influencing mental health and brain function.
The Role of Serotonin in Brain Function
In addition to depression, serotonin may play a role in other brain and mental health disorders, including anxiety disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), phobias, and even epilepsy.
Serotonin plays an important role in many other body functions, too. It’s involved in appetite and digestion (bowel function and bowel movements), bone health, sex, and sleep.
Serotonin is a precursor to melatonin, a chemical that helps regulate the body’s sleep-wake cycle. (2) Certain antidepressants that raise serotonin levels have been associated with sexual dysfunction.
Too high or too low levels of serotonin have been linked to diseases such as irritable bowel syndrome (IBS), heart disease, and osteoporosis — a disease that weakens the bones — according to an article published in April 2016 in the journal Cell. (3)
Gut Bacteria and Serotonin Production
In recent years, scientists have found that gut bacteria help to produce serotonin and that most of the body’s supply of serotonin can actually be found in the lining of the stomach and intestines. (3)
It’s not clear yet whether — or how — altered serotonin levels in the gut influence brain activity. Some researchers have postulated that serotonin in the gut may stimulate the vagus nerve, the long nerve that connects the digestive tract to the brain. (4)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Selective serotonin reuptake inhibitors, or SSRIs, are a class of drugs used to treat depression and anxiety. They’re the most popular class of antidepressants. (5)
Commonly prescribed SSRIs include:
How Do SSRI Drugs Work?
SSRIs are thought to work by increasing serotonin levels in the brain. SSRIs do this by blocking the absorption of serotonin by nerve cells, keeping more of it available for passing along further messages between nerve cells in the brain.
Other groups of antidepressants, called serotonin and norepinephrine reuptake inhibitors (SNRIs) and serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs), block the absorption of serotonin and the other neurotransmitters norepinephrine and dopamine. (5)
SSRIs are sometimes called second generation antidepressants. In general, these antidepressants have fewer side effects than older tricyclic antidepressants.
Still, there are still several common side effects associated with SSRI use. These may include: (6)
- Dry mouth
- Nervousness (jitters)
- Weight gain
- Sexual dysfunction
Some people — especially children, teens, and young adults — may have an increase in suicidal thoughts while taking SSRIs.
These side effects are most common when people first start to take SSRIs — or when they change a dose — and tend to lessen over time.
Who Benefits From Use of SSRIs?
SSRIs appear to work best for people with major or severe depression. A review of studies published in April 2018 in the journal The Lancet found that most antidepressants, including commonly prescribed SSRIs, offered a modest benefit over a placebo treatment for people with major depressive disorder. (7) According to the U.S. National Library of Medicine, antidepressants, including SSRIs, helped to relieve depression symptoms in about 20 percent of people. (8)
The benefits of SSRIs for people with mild to moderate depression remain unclear.
Some researchers have shown that SSRIs are most effective when they are combined with talk or behavior therapies that help depression sufferers learn new strategies for coping with troublesome thoughts. A study published in June 2018 in the journal Nature Communications suggested that serotonin may help to speed learning, which could help to explain these findings. (9)
Serotonin Foods and Supplements
Serotonin isn’t found in foods, but its precursor, tryptophan, is. Tryptophan is an essential amino acid that is important in the production of serotonin. Amino acids are the building blocks of protein.
Scientists have shown that the tryptophan in the diet is linked to levels of serotonin in the brain, with lower amounts of dietary tryptophan causing brain levels of serotonin to drop, according to a review published in January 2016 in the journal Nutrients. (10)
Tryptophan is present in most protein-rich foods. Foods high in tryptophan include:
- Nuts and seeds
- Turkey and other poultry
- Soy foods
Some studies have proposed that eating tryptophan-rich foods may increase levels of serotonin in the brain and help treat depression symptoms. Other studies have found no correlation between tryptophan-rich foods or supplements and depression symptoms, according to a review published in January 2016 in the journal Current Opinion in Clinical Nutrition and Metabolic Care. (11)
Most research indicates that any serotonin boost you might get from eating high-tryptophan foods is probably small. That’s because foods rich in tryptophan tend to be rich in other amino acids as well — and these molecules all have to compete with one another to be absorbed into the brain. (11)
The dietary supplement 5-HTP (5-hydroxytryptophan), a chemical by-product of tryptophan, also helps to increase serotonin production in the brain. (12)
According to the Natural Medicines Comprehensive Database, the dietary supplement may be effective in reducing symptoms of depression in some people. (12)
But larger studies are needed to prove that 5-HTP is safe and effective, and to date 5-HTP has not been approved by the Food and Drug Administration (FDA) as a treatment for depression.
In addition, 5-HTP should not be taken with antidepressant drugs or other depression medication. Many drugs taken for depression or anxiety also raise serotonin levels, and increasing serotonin levels too much can cause serious side effects, including heart problems. (12)
Serotonin syndrome, also called serotonin toxicity, is a rare but potentially life-threatening condition that can happen when serotonin levels are too high. (13)
Serotonin syndrome is most likely to occur when starting an antidepressant medication, increasing the dosage of an antidepressant medication, or when two drugs that raise the body’s levels of serotonin are taken at the same time, causing too much serotonin to accumulate in the brain.
Serotonin-raising medicines include: (14)
- Older antidepressants called monoamine oxidase inhibitors (MAOIs)
- Meperedine (Demerol), a painkiller
- Dextromethorphan (DXM or DM), a cough medicine ingredient
- Migraine drugs called triptans
- 5-HTP or other dietary tryptophan supplements
- Saint-John’s-Wort, an herbal supplement used to treat depression symptoms (15)
- Garcinia cambogia, a tropical fruit and weight loss supplement
If you take any of these medicines, be sure to read the packaging labels for warnings about the potential risks of serotonin syndrome. Talk to your doctor if you have any concerns.
Symptoms of serotonin syndrome usually occur within minutes to hours. They may include: (14)
- Rapid heartbeat or fast pulse
- High blood pressure
- Heavy sweating
- Rapid breathing
- Agitation or restlessness
- Hot, dry skin
- Shivering, goose bumps
- Dilated pupils
- Nausea and vomiting
- Rigid muscles, twitching
- Loss of coordination
Call your healthcare provider immediately if you think you may be experiencing symptoms of serotonin syndrome. Symptoms may vary from mild to severe. Patients with severe serotonin syndrome may require hospitalization in an intensive care unit.
How to boost serotonin and improve mood
Tryptophan, which goes into making serotonin, is commonly found in foods that contain protein. Although meat is often a key source of protein for many people, there are also many vegetarian and vegan sources.
The following foods are good sources of tryptophan:
This oily fish is also a source of omega-3 fatty acids, which are important for health. These fatty acids can help support strong bones, healthy skin, and eye function.
Salmon is also a source of vitamin D, which is essential for strong bones and teeth, and healthy muscles.
Eating two portions of oily fish per week should provide enough tryptophan for most people. Vegans and vegetarians can get omega-3 from pumpkin seeds, walnuts, and soya.
Poultry includes chicken, turkey, and goose. Lean poultry, such as chicken breast, will usually be high in protein and low in fat.
Some ways of cooking and preparing eggs are more healthful than others. Frying an egg adds a lot of fat, which makes it a less healthful option.
Boiling or poaching an egg does not add any additional fat. Making an omelet and eating it with a salad can be a good option for a light meal.
Dark green leafy vegetables, such as spinach, are a source of tryptophan.
Spinach is also a good source of iron. Iron helps the body to make healthy red blood cells. A lack of iron in the diet can lead to anemia, low energy, or difficulty breathing.
Share on PinterestSeeds are a plant source of tryptophan.
Seeds do not contain as much tryptophan as oily fish, poultry, or eggs. However, they are a good source of tryptophan and protein for vegetarians and vegans.
Some easy ways to eat more seeds include:
- sprinkling seeds onto a salad
- mixing nuts and seeds for a snack
- choosing seeded bread
- adding seeds to cereal, porridge, or yogurt
Milk is also a good source of calcium, which helps to build healthy bones and teeth.
Choosing a low-fat option can be more healthful than full-fat milk, particularly for people watching their saturated fat intake.
7. Soy products
Products containing soy, such as tofu, soya milk, or soy sauce, are a source of tryptophan. These can be a good option for vegetarians and vegans.
Nuts are a good source of protein, healthful fats, and fiber. Snacking on a few nuts between meals can help a person to feel fuller for longer.
Have you ever wondered what hormone is responsible for your mood and feelings? Serotonin is the key hormone that stabilizes our mood, feelings of well-being, and happiness. This hormone impacts your entire body. It enables brain cells and other nervous system cells to communicate with each other. Serotonin also helps with sleeping, eating, and digestion. However, if the brain has too much serotonin, it may lead to depression. If the brain has too much serotonin, it can lead to excessive nerve cell activity. It also helps reduce depression, regulate anxiety, and maintain bone health.
How Does Your Body Use Serotonin?
Your body uses serotonin in various ways:
- Serotonin is in the brain. It is thought to regulate mood, happiness, and anxiety. Low levels of serotonin are linked to depression, while increased levels of the hormone may decrease arousal.
- Serotonin is found in your stomach and intestines. It helps control your bowel movements and function.
- Serotonin is produced when you become nauseated. Production of serotonin increases to help remove bad food or other substances from the body. It also increases in the blood, which stimulates the part of the brain that controls nausea.
- Serotonin is responsible for stimulating the parts of the brain that control sleep and waking. Whether you sleep or wake depends on the area is stimulated and which serotonin receptor is used.
- Serotonin is released to help heal wounds. Serotonin triggers tiny arteries to narrow, which helps forms blood clots.
- Having very high levels of serotonin in the bones can lead to osteoporosis, which makes the bones weaker.
How Does Serotonin Impact Your Mental Health?
Serotonin helps regulate your mood naturally. When your serotonin levels are at a normal level, you should feel more focused, emotionally stable, happier, and calmer.
What Problems are Associated with Low Levels of Serotonin?
Low levels of serotonin are often associated with many behavioral and emotional disorders. Studies have shown that low levels of serotonin can lead to depression, anxiety, suicidal behavior, and obsessive-compulsive disorder. If you are experiencing any of these thoughts or feelings, consult a health care professional immediately. The sooner treatment starts, the faster you’ll see improvements.
What Problems are Associated with High Levels of Serotonin?
Serotonin syndrome can occur when you take medications that increase serotonin action leading to side effects. Too much serotonin can cause mild symptoms such as shivering, heavy sweating, confusion, restlessness, headaches, high blood pressure, twitching muscles, and diarrhea. More severe symptoms include high fever, unconsciousness, seizures, or irregular heartbeat. Serotonin syndrome can happen to anyone, but some people may be at higher risk. You are at a higher risk if you increased the dose of medication that is known to raise serotonin levels or take more than one drug known to increase serotonin. You may also be at risk if you take herbal supplements or an illicit drug known to increase serotonin levels.
Questions to Ask Your Healthcare Team
If you suspect that your serotonin levels are too high or low, the first step is to speak with a health care professional. Consider asking your doctor:
- Is my medication causing serotonin syndrome?
- If I am experiencing feelings of depression, are my serotonin levels too low?
- Are my levels of serotonin affecting any other aspects of my health?
Serotonin and Serotonin Deficiency
SEROTONIN is one of the most widely recognized (and a frequently searched term on google.com) of all neurotransmitters. It is intricately involved in numerous core physical processes such as the regulation of sleep, appetite and aggression. Serotonin is also a key player in mood, anxiety, fear, and general sense of well-being. Imbalances in serotonin, particularly relative to norepinephrine and dopamine, are common causes of certain types of depression. Antidepressants that block serotonin’s re-uptake back into serotonin neurons are among the most common of all classes of medications prescribed.
Serotonin deficiency is a common contributor to mood problems. Some feel it is an epidemic in the United States. Serotonin is key to our feelings of happiness and very important for our emotions because it helps defend against both anxiety and depression. Many of the current biochemical theories of depression focus on the biogenic amines, which are a group of chemical compounds important in neurotransmission—most importantly norepinephrine, serotonin and, to a lesser extent, dopamine, acetylcholine and epinephrine.
What causes or contributes to Serotonin Deficiency?
Many life stressors can lead to low serotonin:
- Prolonged periods of stress can deplete serotonin levels. Our fast paced, fast food society greatly contributes to these imbalances.
- Genetic factors, faulty metabolism, and digestive issues can impair absorption and breakdown of our food which reduces are ability to build serotonin.
- Poor Diet. Neurotransmitters are made in the body from proteins. Also required are certain vitamins and minerals called “cofactors”. If your nutrition is poor and you do not take in enough protein, vitamins, or minerals to build the neurotransmitters, a neurotransmitter imbalance develops. We really do think and feel what we eat.
- Toxic substances like heavy metals, pesticides, drug use, and some prescription drugs can cause permanent damage to the nerve cells that make serotonin and other neurotransmitters.
- Certain drugs and substances such as caffeine, alcohol, nicotine, NutraSweet, antidepressants, and some cholesterol lowering medications deplete serotonin and other neurotransmitter levels.
- Hormone changes cause low levels of serotonin and neurotransmitter imbalances.
- Lack of sunlight contributes to low serotonin levels
You may have a shortage of serotonin if you have a sad depressed mood, low energy, negative thoughts, feel tense and irritable, crave sweets, and have a reduced interest in sex. Other serotonin related disorders include:
- Panic Attacks
- Irritable bowel
- PMS/ Hormone dysfunction
- Eating disorders
- Obsessions and Compulsions
- Muscle pain
- Chronic Pain
- Alcohol abuse
- Migraine Headaches
How do I know if Serotonin is deficient?
Neurotransmitter testing, Questionnaires, and blood testing can help determine if you might have a serotonin deficiency. Certain tests can determine if you have normal levels of the precursors and co-factor vitamins and minerals needed for the brain to produce serotonin. Additionally, hormones such as Adrenal, Thyroid, and Estrogen levels can affect serotonin levels and may explain why some women have pre-menstrual and menopausal mood problems.
How to raise serotonin levels naturally
Prescription drugs such as Prozac, Zoloft, Paxil, and Lexapro are classified as serotonin reuptake inhibitors, or (SSRI’s). They help to keep more of the serotonin your brain is making in circulation. They do not, however, increase your brain’s supply of serotonin. Some studies, in fact, indicate that over time they may actually accelerate your turnover of serotonin thereby making your serotonin deficiency worse. They are used for a wide variety of symptoms such as depression, panic attacks, anxiety, PTSD, obsessions, and compulsions. There are also serotonin/norepinephrine re-uptake inhibitors (SNRI’s) such as Effexor and Cymbalta that keep more serotonin and norepinephrine in circulation. Again, such agents do not help you build more neurotransmitters.
Find out more about the serotonin and norepinephrine suppplements we have available!
Nutrient therapies such as Targeted Amino Acid Therapy naturally increase the levels of neurotransmitters that a person has been found to be deficient in.5 hydroxytryptophan and Tryptophan are widely known for their ability to help depressive symptoms by raising serotonin levels in the brain.. Numerous clinical trials have studied the efficacy of 5-HTP for treating depression. One compared 5-HTP to the antidepressant drug fluvoxamine and found 5-HTP to be equally effective.
It can be used alone or in combination with medication to keep dosages low and to prevent the “poop out” many people experience with medication.
- tryptophan —> 5-HTP —> serotonin
Herbal Remedies such as St. Johns Wort are available to alleviate symptoms of depression and anxiety. Some work in a similar way to the SSRI antidepressants.
Things you can do to increase your serotonin levels and improve overall health.
- Exercise at least 30 minutes three times a week.
- Walking, yoga, stretching.
- Get plenty of sunlight.
- Drink 6-8 glasses of water daily
- Prayer and meditation
Eat at least three meals per day. Skipping meals promotes high stress and low energy. Eat protein with every meal. Eat Complex carbohydrates such as brown rice. Avoid sugar, junk food, white pasta, white rice, white bread, cookies and cake. No Caffeine, alcohol, or NutraSweet (aspartame). NutraSweet can be toxic to your brain. Alcohol can worsen depression, anxiety, and sleep problems.
If you’ve ever fallen down the Google rabbit hole, researching ways to boost your mood (or is that just me?), you’ve likely heard about serotonin, a neurotransmitter in the brain that’s linked to better mood and overall satisfaction. And it’s tempting to wonder how to increase serotonin, since it seemingly is the thing that makes you happier.
However, serotonin actually offers up quite a few additional benefits for your health. Besides helping regulate mood, serotonin is also needed for motor skills and cognitive functioning. It’s also included in nerve function that regulates blood pressure, heart rate, and the digestion system. So it’s pretty darn important.
While boosting your brain’s serotonin could help boost your mood, too, it’s not a panacea for every mental health issue. Integrative psychiatrist James Lake, MD, warns that managing depression—or even just a bad mood—is much more complicated than zeroing in on serotonin. “Serotonin is certainly an important neurotransmitter and important in that equation, but there are numerous other neurotransmitters that are important, too,” he says. Besides serotonin, dopamine, oxytocin, and endorphins all play important roles in regulating mood. And if you’re truly struggling with what you believe to be a serious mood or mental health condition,
With this in mind, there are several ways to naturally boost your serotonin levels. Keep reading to see what they are.
Scroll down for 5 tips on how to increase serotonin.
1. Tweak your diet. Depending on what you eat, you could be replenishing the serotonin in your brain—or depleting it. “Nutritional deficiencies can directly lead to problems with replenishing serotonin,” Dr. Lake says. This is something Well+Good Council member and psychiatrist Drew Ramsey, MD preaches on the reg. “We now have real evidence to back up what’s good common sense: that eating well doesn’t just benefit your body, but it also benefits your brain,” he previously told Well+Good.
Dr. Ramsey has said that the Mediterranean diet is especially beneficial for boosting happiness because omega-3 fats, vitamin B12, zinc, magnesium, and iron boost brain health while lowering inflammation.
2. Get consistent, good sleep. “People who are depressed or have other mental health problems are often not sleeping enough or sleeping too much,” Dr. Lake says. And this could affect your body’s ability to use or make serotonin. One study in rats found that being chronically sleep deprived could affect the brain’s serotonin receptors, making them not as sensitive to the positive effects of serotonin. (The finding was on rats though, which isn’t totally conclusive for humans.) Aim to get between seven to eight hours of good sleep a night.
3. Take a vitamin D supplement. Multiple studies have connected vitamin D deficiencies with mental health conditions; the thinking goes that vitamin D (along with omega-3 fatty acids) helps facilitate serotonin production. Talk to your doctor to see if a vitamin D supplement is something worth considering.
4. Go for a walk in the sunshine. One way to get enough vitamin D is by spending some time outside, which is why many people tend to feel a drop in mood during the winter months. If you’re feeling down, try making afternoon walks a prioritize to up the amount of vitamin D you’re getting, which in turn may help boost your serotonin levels.
5. Take steps to lower stress. Surprise, surprise: stress is totally messing with your serotonin. “Stress is a chronic inflammatory condition, both in the brain and in the body itself,” Dr. Lake says. “It can indirectly result in damage to neurons that produce serotonin or the other parts of the brain that are involved and the serotoninic pathways that make the system work less effectively.” In other words, stress causes inflammation, which is bad news for your brain. Prioritizing self-care, therapy, and other stress-reduction tactics could go a long way towards better health, including better serotonin levels.
Does serotonin have any side effects?
Like all good things, it is possible to get too much serotonin. But this generally only happens as a rare side effect of certain SSRIs (selective serotonin reuptake inhibitors, a type of medication commonly used to manage depression and anxiety), or combining SSRIs. According to the Mayo Clinic, the body’s serotonin levels can artificially become too high, causing symptoms like increased nervousness, insomnia, nausea, diarrhea, tremors, and dilated pupils—and should be addressed immediately with medical attention.
Again, Dr. Lake emphasizes that regulating mood and managing depression is really complicated; it isn’t as easy as finding a way to boost your serotonin and that’s it. But doing so can help with milder mood issues. Give the above tips a shot and see how you feel. And if they don’t work, talk to a mental health professional who can offer other science-backed ways to improve your mood.
Looking to improve your whole week? Here’s one beauty editor’s weekly mental health routine:
Relationships also play a role in boosting happiness. So does sex.
Know your serotonin: An interview with gut-brain axis researcher Elaine Hsiao
Right now, nerve cells in your body are passing a certain neurotransmitter—serotonin—back and forth like a chemical basketball. Well-known for its mood-modulating capacity, this chemical is made both in the digestive tract and the brain. And many researchers believe we still haven’t unlocked all its secrets.
Elaine Hsiao, a researcher at University of California, Los Angeles (USA), studies serotonin in the context of the gut-brain axis—in particular, how molecule and cell activities link the gut microbiota to the brain. GMFH editors caught up with Hsiao at the Harvard Probiotics Symposium to get the latest on serotonin, the brain, and the microbes in your gut.
What’s the difference between serotonin made in the gut and serotonin made in the brain?
The serotonin made in the gut is the same structurally as the serotonin in the brain—they’re the same molecules that are made, but they’re just localized in different places and made by different cells.
In the gut, they’re made primarily by endocrine cells called enterochromaffin cells; some of the gut neurons can also make it, and some of the immune cells can potentially make it, too. Whereas in the brain, there’s a specific subtype of neurons, raphe neurons, that are known to make serotonin and supply the adult brain with it. So they’re the same molecule but made by different cell types, and as such, can elicit different localized functions.
How do microbes help make gut serotonin?
Our work has shown that particular species from the gut microbiome stimulate gut endocrine cells to produce serotonin. So it’s teamwork between microbes and host cells.
As a result of stimulating gut serotonin, we observe more serotonin in the colon, and also more serotonin that is picked up by blood platelets and circulated systemically.
Is more serotonin always good?
No. As with most things, everything in moderation. Too much serotonin has been linked with particular diseases or infections and inflammation. But there are some cases where there are deficiencies in serotonin that are detrimental as well.
How does the gut-based serotonin affect brain development and behaviour?
This is a question we are actively working on.
We started this work because the majority of pathways that are theorized to link gut microbes to the brain and behaviour seem to require, at some point, something that influences neuron activity, and neurotransmitters seemed like likely candidates for that. That’s why we decided to study the neurotransmitter serotonin.
More broadly in the gut-brain axis, what are some of the ways the gut microbiota influence the brain?
Most of the evidence right now supports one pathway which is indirect, where gut microbes modulate the immune system, and there’s a neuro-immune connection.
Other proposed pathways involve microbial modulation of neuroactive molecules that enter the brain itself, or microbial modulation of peripheral neurons that extend into the brain.
Researchers know the gut and the brain are in constant communication, and the role of the gut microbiota in this communication is a hot topic of scientific study. Further work by Elaine Hsiao and others around the globe, focusing on mechanisms of gut-brain interaction, could lead to new insights about how your gut microbes influence your brain and behaviour.
Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota
Serotonin — a neurotransmitter, or chemical messenger that sends messages among cells — serves many functions in the human body, including playing a role in emotions and happiness. An estimated 90% of the body’s serotonin is produced in the gut, where it influences gut immunity.
The team — led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow — identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology.
“Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so,” said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA.
Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao’s team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.
That study got the team wondering why bacteria signal to our gut cells to make serotonin. Do microbes use serotonin, and if so, for what?
In this new study, the researchers added serotonin to the drinking water of some mice and raised others with a mutation (created by altering a specific serotonin transporter gene) that increased the levels of serotonin in their guts. After studying the microbiota of the mice, the researchers discovered that the bacteria Turicibacter and Clostridia increased significantly when there was more serotonin in the gut.
If these bacteria increase in the presence of serotonin, perhaps they have some cellular machinery to detect serotonin, the researchers speculated. Together with study co-author Lucy Forrest and her team at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, the researchers found a protein in multiple species of Turicibacter that has some structural similarity to a protein that transports serotonin in mammals. When they grew Turicibacter sanguinis in the lab, they found that the bacterium imports serotonin into the cell.
In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the mammalian serotonin transporter, to a tube containing Turicibacter sanguinis. They found the bacterium transported significantly less serotonin.
The team found that exposing Turicibacter sanguinis to serotonin or fluoxetine influenced how well the bacterium could thrive in the gastrointestinal tract. In the presence of serotonin, the bacterium grew to high levels in mice, but when exposed to fluoxetine, the bacterium grew to only low levels in mice.
“Previous studies from our lab and others showed that specific bacteria promote serotonin levels in the gut,” Fung said. “Our new study tells us that certain gut bacteria can respond to serotonin and drugs that influence serotonin, like anti-depressants. This is a unique form of communication between bacteria and our own cells through molecules traditionally recognized as neurotransmitters.”
The team’s research on Turicibacter aligns with a growing number of studies reporting that anti-depressants can alter the gut microbiota. “For the future,” Hsiao said, “we want to learn whether microbial interactions with antidepressants have consequences for health and disease.” Hsiao wrote a blog post for the journal about the new research.
Frequently Asked Questions about Serotonin
Serotonin is a common neurotransmitter found in our brains. Neurotransmitters are special chemicals in our brain that help relay signals from one area of the brain to another. Although serotonin is manufactured in the brain, where it performs its primary functions, some 90% of our serotonin supply is found in the digestive tract and in blood platelets. The average adult has between five and 10 milligrams of serotonin in the body.
Q. What role does serotonin play in our health?
As a neurotransmitter, serotonin helps to relay messages from one area of the brain to another. Because of the widespread distribution of its cells, it is believed to influence a variety of psychological and other body functions. Of the approximately 40 million brain cells, most are influenced either directly or indirectly by serotonin. This includes brain cells related to mood, sexual desire and function, appetite, sleep, memory and learning, temperature regulation, and some social behavior.
In terms of our body function, serotonin can also affect the functioning of our heart, muscles, and various elements in the endocrine system. Researchers have also found evidence that serotonin may play a role in regulating milk production in the breast, and that a defect within the serotonin network may be one underlying cause of SIDS (sudden infant death syndrome).
Q. What is the link between serotonin and depression?
There are many researchers who believe that an imbalance in serotonin levels may influence mood in a way that leads to depression. Possible problems include low brain cell production of serotonin, a lack of receptor sites able to receive the serotonin that is made, inability of serotonin to reach the receptor sites, or a shortage in tryptophan, the chemical from which serotonin is made. If any of these biochemical glitches occur, researchers believe it can lead to depression, as well as obsessive-compulsive disorder, anxiety, panic, and even excess anger.
One of the newest theories about depression centers on the regeneration of brain cells — a process that some believe is mediated by serotonin, and ongoing throughout our lives. According to Princeton neuroscientist Barry Jacobs, PhD, depression may occur when there is a suppression of new brain cells and that stress is the most important precipitator of depression. He believes that common antidepressant medications, such as Celexa, Lexapro, Prozac, and Paxil — designed to boost serotonin levels — help kick off the production of new brain cells, which in turn allows the depression to lift.
Although it is widely believed that a serotonin deficiency plays a role in depression, there is no way to measure its levels in the living brain. Therefore, there have not been any studies proving that brain levels of this or any neurotransmitter are in short supply when depression or any mental illness develops. And while blood levels of serotonin are measurable — and have been shown to be lower in people who suffer from depression — what doctors still don’t know for certain is whether or not the dip in serotonin causes the depression, or the depression causes serotonin levels to drop.
Antidepressant medications that work on serotonin levels — medications known as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) are believed to reduce symptoms of depression, but exactly how they work is not yet fully understood.
Q. Can diet influence our supply of serotonin?
It can, but in a roundabout way. Unlike calcium-rich foods, which can directly increase your blood levels of this mineral, there are no foods that can directly increase your body’s supply of serotonin. That said, there are foods and some nutrients that can increase levels of tryptophan, the amino acid from which serotonin is made.
Eating a carbohydrate-rich meal will have your body trigger a release of insulin. This in turn causes any amino acids in the blood to be absorbed into the body except for tryptophan. It remains in the bloodstream at high levels following a carbohydrate meal, which means it can freely enter the brain and cause serotonin levels to rise.
Getting an adequate supply of vitamin B-6, which can influence the rate at which tryptophan is converted to serotonin.
Frequently Asked Questions about Serotonin
Microbes Help Produce Serotonin in Gut
Although serotonin is well known as a brain neurotransmitter, it is estimated that 90 percent of the body’s serotonin is made in the digestive tract. In fact, altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis. New research at Caltech, published in the April 9 issue of the journal Cell, shows that certain bacteria in the gut are important for the production of peripheral serotonin.
“More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,” explains Elaine Hsiao, research assistant professor of biology and biological engineering and senior author of the study. “We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.”
Peripheral serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons. Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes.
The researchers found that the EC cells from germ-free mice produced approximately 60 percent less serotonin than did their peers with conventional bacterial colonies. When these germ-free mice were recolonized with normal gut microbes, the serotonin levels went back up—showing that the deficit in serotonin can be reversed.
“EC cells are rich sources of serotonin in the gut. What we saw in this experiment is that they appear to depend on microbes to make serotonin—or at least a large portion of it,” says Jessica Yano, first author on the paper and a research technician working with Hsiao.
The researchers next wanted to find out whether specific species of bacteria, out of the diverse pool of microbes that inhabit the gut, are interacting with EC cells to make serotonin.
After testing several different single species and groups of known gut microbes, Yano, Hsiao, and colleagues observed that one condition—the presence of a group of approximately 20 species of spore-forming bacteria—elevated serotonin levels in germ-free mice. The mice treated with this group also showed an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.
Wanting to home in on mechanisms that could be involved in this interesting collaboration between microbe and host, the researchers began looking for molecules that might be key. They identified several particular metabolites—products of the microbes’ metabolism—that were regulated by spore-forming bacteria and that elevated serotonin from EC cells in culture. Furthermore, increasing these metabolites in germ-free mice increased their serotonin levels.
Previous work in the field indicated that some bacteria can make serotonin all by themselves. However, this new study suggests that much of the body’s serotonin relies on particular bacteria that interact with the host to produce serotonin, says Yano. “Our work demonstrates that microbes normally present in the gut stimulate host intestinal cells to produce serotonin,” she explains.
“While the connections between the microbiome and the immune and metabolic systems are well appreciated, research into the role gut microbes play in shaping the nervous system is an exciting frontier in the biological sciences,” says Sarkis K. Mazmanian, Luis B. and Nelly Soux Professor of Microbiology and a coauthor on the study. “This work elegantly extends previous seminal research from Caltech in this emerging field”.
Additional coauthor Rustem Ismagilov, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering, adds, “This work illustrates both the richness of chemical interactions between the hosts and their microbial communities, and Dr. Hsiao’s scientific breadth and acumen in leading this work.”
Serotonin is important for many aspects of human health, but Hsiao cautions that much more research is needed before any of these findings can be translated to the clinic.
“We identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explored,” she says. “Also, there are conditions where an excess of peripheral serotonin appears to be detrimental.”
Although this study was limited to serotonin in the gut, Hsiao and her team are now investigating how this mechanism might also be important for the developing brain. “Serotonin is an important neurotransmitter and hormone that is involved in a variety of biological processes. The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology,” says Hsiao.
The work was published in an article titled “Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis.” In addition to Hsiao, Yano, Mazmanian, and Ismagilov, other Caltech coauthors include undergraduates Kristie Yu, Gauri Shastri, and Phoebe Ann; graduate student Gregory Donaldson; postdoctoral scholar Liang Ma. Additional coauthor Cathryn Nagler is from the University of Chicago.
This work was funded by an NIH Director’s Early Independence Award and a Caltech Center for Environmental Microbial Interactions Award, both to Hsiao. The study was also supported by NSF, NIDDK, and NIMH grants to Mazmanian, NSF EFRI and NHGRI grants to Ismagilov, and grants from the NIAID and Food Allergy Research and Education and University of Chicago Digestive Diseases Center Core to Nagler.
Serotonin, the brain chemical best known for its link to depression, may also be involved in autism.
Serotonin has many roles throughout the body, including in mood, sleep, appetite and sociability. In the intestines, it stimulates muscles involved in digestion; in the blood, it causes vessels to shrink or expand; and in the brain, it relays messages between neurons. Its levels in the brain are closely tied to depression. Many antidepressants work by increasing the levels of serotonin at neuronal junctions.
Tenuous ties between serotonin and autism first surfaced decades ago. In 1961, a study of 23 autistic people reported that 6 of them had an unusually high level of serotonin in their blood. Since then, researchers have consistently found that about one in four people on the spectrum has high blood serotonin.
That result is “incredibly well replicated,” says Jeremy Veenstra-VanderWeele, professor of psychiatry at Columbia University.
Motivated in part by these results, several research teams have tested antidepressants as a treatment for autism over the past 20 years — with mixed results. Interest in serotonin’s role in autism has grown in the past five years, due in part to mouse studies that implicate the chemical in social behavior.
Here’s what we know so far about serotonin’s role in autism.
What could explain the high serotonin levels in the blood of people with autism?
Blood serotonin levels are controlled in part by a protein called the serotonin transporter, which moves serotonin from the gut, where most serotonin is made, into certain blood cells.
These levels are highly heritable, suggesting that genetic factors control them.
Some people with autism may carry variants in the serotonin transporter that enhance its ability to move serotonin into blood cells1. Mice with these variants have unusually high blood levels of serotonin and behaviors reminiscent of autism2.
What does serotonin do in the brain?
In the fetus, serotonin helps neurons form and travel to their correct locations; it also helps them link to other neurons at junctions called synapses3. Too much or too little serotonin can be harmful: Mice exposed to too much in utero show altered development in a brain region that responds to whisker movements4; those with too little have repetitive behaviors and social difficulties5.
In the mature brain, serotonin is a neurotransmitter: It relays messages between neurons. Its level at the synapse is tightly controlled by the serotonin transporter, which pumps serotonin back into neurons and recycles it for later use. This transporter may be altered in people with autism6.
What do blood levels of serotonin have to do with serotonin in the brain?
It is unclear, because serotonin in the blood cannot pass into the brain; the brain makes its own. Genetic variants that turbocharge the transport of serotonin into blood cells are predicted to have the same effect in neurons, effectively leaving less of it available to relay messages across synapses. Antidepressants might be able to help by restoring levels of serotonin at the synapse.
How does the brain’s serotonin level relate to autism?
Some studies point to low serotonin levels in the brains of autistic people.
When autistic adults adopt a diet low in the amino acid tryptophan — the raw material for serotonin — their repetitive behaviors worsen and their irritability increases7. They also show altered patterns of brain activity in regions involved in face processing, suggesting that serotonin influences social behavior8.
Brain-imaging studies also hint that some autistic children make too little serotonin in the brain, and in others, too little serotonin binds to its receptors9,10.
Can treatments that increase serotonin levels ease autism traits?
Possibly. Antidepressants that allow serotonin to remain at the synapse for longer seem to ease repetitive behaviors in some autistic adults11. These drugs, called selective serotonin reuptake inhibitors (SSRIs), have not yet been shown to benefit children with autism. But clinical trials of these drugs are hampered by powerful placebo effects that might make it hard to tease out the benefit.
Preliminary evidence suggests that in adults with autism, the active ingredient in the drug ‘ecstasy,’ which raises serotonin levels in the brain, seems to ease social anxiety.
Some mouse models of autism have low brain serotonin levels. Treating one such strain of mice with an SSRI starting at birth prevents autism-like social behaviors. And artificially boosting serotonin in in another mouse model makes the mice more social.
Do serotonin levels in utero affect a child’s autism risk?
Some studies have explored whether exposure to antidepressants in utero has any effect on autism risk. The answer is unclear. One problem is that researchers are often not able to separate the effect of the antidepressant from that of the mother’s underlying depression. Simply having a family history of depression, for example, is associated with autism.
Where is research on serotonin and autism headed?
Some researchers are testing whether drugs that activate serotonin receptors make mouse models of autism more sociable. Others are working on strategies that dampen the activity of the serotonin transporter without blocking it completely12.
As Olympians go for the gold in Vancouver, even the steeliest are likely to experience that familiar feeling of “butterflies” in the stomach. Underlying this sensation is an often-overlooked network of neurons lining our guts that is so extensive some scientists have nicknamed it our “second brain”.
A deeper understanding of this mass of neural tissue, filled with important neurotransmitters, is revealing that it does much more than merely handle digestion or inflict the occasional nervous pang. The little brain in our innards, in connection with the big one in our skulls, partly determines our mental state and plays key roles in certain diseases throughout the body.
Although its influence is far-reaching, the second brain is not the seat of any conscious thoughts or decision-making.
“The second brain doesn’t help with the great thought processes…religion, philosophy and poetry is left to the brain in the head,” says Michael Gershon, chairman of the Department of Anatomy and Cell Biology at New York–Presbyterian Hospital/Columbia University Medical Center, an expert in the nascent field of neurogastroenterology and author of the 1998 book The Second Brain (HarperCollins).
Technically known as the enteric nervous system, the second brain consists of sheaths of neurons embedded in the walls of the long tube of our gut, or alimentary canal, which measures about nine meters end to end from the esophagus to the anus. The second brain contains some 100 million neurons, more than in either the spinal cord or the peripheral nervous system, Gershon says.
This multitude of neurons in the enteric nervous system enables us to “feel” the inner world of our gut and its contents. Much of this neural firepower comes to bear in the elaborate daily grind of digestion. Breaking down food, absorbing nutrients, and expelling of waste requires chemical processing, mechanical mixing and rhythmic muscle contractions that move everything on down the line.
Thus equipped with its own reflexes and senses, the second brain can control gut behavior independently of the brain, Gershon says. We likely evolved this intricate web of nerves to perform digestion and excretion “on site,” rather than remotely from our brains through the middleman of the spinal cord. “The brain in the head doesn’t need to get its hands dirty with the messy business of digestion, which is delegated to the brain in the gut,” Gershon says. He and other researchers explain, however, that the second brain’s complexity likely cannot be interpreted through this process alone.
“The system is way too complicated to have evolved only to make sure things move out of your colon,” says Emeran Mayer, professor of physiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles (U.C.L.A.). For example, scientists were shocked to learn that about 90 percent of the fibers in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around. “Some of that info is decidedly unpleasant,” Gershon says.
The second brain informs our state of mind in other more obscure ways, as well. “A big part of our emotions are probably influenced by the nerves in our gut,” Mayer says. Butterflies in the stomach—signaling in the gut as part of our physiological stress response, Gershon says—is but one example. Although gastrointestinal (GI) turmoil can sour one’s moods, everyday emotional well-being may rely on messages from the brain below to the brain above. For example, electrical stimulation of the vagus nerve—a useful treatment for depression—may mimic these signals, Gershon says.
Given the two brains’ commonalities, other depression treatments that target the mind can unintentionally impact the gut. The enteric nervous system uses more than 30 neurotransmitters, just like the brain, and in fact 95 percent of the body’s serotonin is found in the bowels. Because antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels, it’s little wonder that meds meant to cause chemical changes in the mind often provoke GI issues as a side effect. Irritable bowel syndrome—which afflicts more than two million Americans—also arises in part from too much serotonin in our entrails, and could perhaps be regarded as a “mental illness” of the second brain.
Scientists are learning that the serotonin made by the enteric nervous system might also play a role in more surprising diseases: In a new Nature Medicine study published online February 7, a drug that inhibited the release of serotonin from the gut counteracted the bone-deteriorating disease osteoporosis in postmenopausal rodents. (Scientific American is part of Nature Publishing Group.) “It was totally unexpected that the gut would regulate bone mass to the extent that one could use this regulation to cure—at least in rodents—osteoporosis,” says Gerard Karsenty, lead author of the study and chair of the Department of Genetics and Development at Columbia University Medical Center.
Serotonin seeping from the second brain might even play some part in autism, the developmental disorder often first noticed in early childhood. Gershon has discovered that the same genes involved in synapse formation between neurons in the brain are involved in the alimentary synapse formation. “If these genes are affected in autism,” he says, “it could explain why so many kids with autism have GI motor abnormalities” in addition to elevated levels of gut-produced serotonin in their blood.
Down the road, the blossoming field of neurogastroenterology will likely offer some new insight into the workings of the second brain—and its impact on the body and mind. “We have never systematically looked at in relating lesions in it to diseases like they have for the” central nervous system, Gershon says. One day, perhaps there will be well-known connections between diseases and lesions in the gut’s nervous system as some in the brain and spinal cord today indicate multiple sclerosis.
Cutting-edge research is currently investigating how the second brain mediates the body’s immune response; after all, at least 70 percent of our immune system is aimed at the gut to expel and kill foreign invaders.
U.C.L.A.’s Mayer is doing work on how the trillions of bacteria in the gut “communicate” with enteric nervous system cells (which they greatly outnumber). His work with the gut’s nervous system has led him to think that in coming years psychiatry will need to expand to treat the second brain in addition to the one atop the shoulders.
So for those physically skilled and mentally strong enough to compete in the Olympic Games—as well as those watching at home—it may well behoove us all to pay more heed to our so-called “gut feelings” in the future.
For the last 4 decades, the question of how to manipulate the serotonergic system with drugs has been an important area of research in biological psychiatry, and this research has led to advances in the treatment of depression. Research on the association between various polymorphisms and depression supports the idea that serotonin plays a role, not only in the treatment of depression but also in susceptibility to depression and suicide. The research focus here has been on polymorphisms of the serotonin transporter, but other serotonin-related genes may also be involved.1–5 In the future, genetic research will make it possible to predict with increasing accuracy who is susceptible to depression. Much less attention has been given to how this information will be used for the benefit of individuals with a serotonin-related susceptibility to depression, and little evidence exists concerning strategies to prevent depression in those with such a susceptibility. Various studies have looked at early intervention in those with prodromal symptoms as well as at population strategies for preventing depression.6–11 Obviously, prevention is preferable to early intervention; moreover, although population strategies are important, they are ideally supplemented with preventive interventions that can be used over long periods of time in targeted individuals who do not yet exhibit even nonclinical symptoms. Clearly, pharmacologic approaches are not appropriate, and given the evidence for serotonin’s role in the etiology and treatment of depression, nonpharmacologic methods of increasing serotonin are potential candidates to test for their ability to prevent depression.
Another reason for pursuing nonpharmacologic methods of increasing serotonin arises from the increasing recognition that happiness and well-being are important, both as factors protecting against mental and physical disorders and in their own right.12–14 Conversely, negative moods are associated with negative outcomes. For example, the negative mood hostility is a risk factor for many disorders. For the sake of brevity, hostility is discussed here mainly in relation to one of the biggest sources of mortality, coronary heart disease (CHD). A meta-analysis of 45 studies demonstrated that hostility is a risk factor for CHD and for all-cause mortality.15 More recent research confirms this. Hostility is associated not only with the development of CHD but also with poorer survival in coronary artery disease (CAD) patients.16 Hostility may lead to decreased social support and social isolation,17 and low perceived social support is associated with greater mortality in those with CAD.18 Effects are not just limited to CHD. For example, the opposite of hostility, agreeableness, was a significant protective factor against mortality in a sample of older, frail participants.19
The constitution of the WHO states “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.”20 This may sound exaggerated but positive mood within the normal range is an important predictor of health and longevity. In a classic study, those in the lowest quartile for positive emotions, rated from autobiographies written at a mean age of 22 years, died on average 10 years earlier than those in the highest quartile.21 Even taking into account possible confounders, other studies “found the same solid link between feeling good and living longer.”12 In a series of recent studies, negative emotions were associated with increased disability due to mental and physical disorders,22 increased incidence of depression,23 increased suicide24 and increased mortality25 up to 2 decades later. Positive emotions protected against these outcomes. A recent review including meta-analyses assessed cross-sectional, longitudinal and experimental studies and concluded that happiness is associated with and precedes numerous successful outcomes.26 Mood may influence social behaviour, and social support is one of the most studied psychosocial factors in relation to health and disease.27 Low social support is associated with higher levels of stress, depression, dysthymia and posttraumatic stress disorder and with increased morbidity and mortality from a host of medical illnesses.27
Research confirms what might be intuitively expected, that positive emotions and agreeableness foster congenial relationships with others.28,29 This in turn will create the conditions for an increase in social support.
Several studies found an association between measures related to serotonin and mood in the normal range. Lower platelet serotonin2 receptor function was associated with lower mood in one study,30 whereas better mood was associated with higher blood serotonin levels in another.31 Two studies found that greater prolactin release in response to fenfluramine was associated with more positive mood.32,33 The idea that these associations indicate a causal association between serotonin function and mood within the normal range is consistent with a study demonstrating that, in healthy people with high trait irritability, tryptophan, relative to placebo, decreased quarrelsome behaviours, increased agreeable behaviours and improved mood.34 Serotonin may be associated with physical health as well as mood. In otherwise healthy individuals, a low prolactin response to the serotonin-releasing drug fenfluramine was associated with the metabolic syndrome, a risk factor for heart disease,35 suggesting that low serotonin may predispose healthy individuals to suboptimal physical as well as mental functioning.
Nonpharmacologic methods of raising brain serotonin may not only improve mood and social functioning of healthy people — a worthwhile objective even without additional considerations — but would also make it possible to test the idea that increases in brain serotonin may help protect against the onset of various mental and physical disorders. Four strategies that are worth further investigation are discussed below.
The article by Perreau-Linck and colleagues36 (page 430 of this issue) provides an initial lead about one possible strategy for raising brain serotonin. Using positron emission tomography, they obtained a measure of serotonin synthesis in the brains of healthy participants who underwent positive, negative and neutral mood inductions. Reported levels of happiness were positively correlated and reported levels of sadness were negatively correlated with serotonin synthesis in the right anterior cingulate cortex. The idea that alterations in thought, either self-induced or due to psychotherapy, can alter brain metabolism is not new. Numerous studies have demonstrated changes in blood flow in such circumstances. However, reports related to specific transmitters are much less common. In one recent study, meditation was reported to increase release of dopamine.37 The study by Perreau-Linck and colleagues36 is the first to report that self-induced changes in mood can influence serotonin synthesis. This raises the possibility that the interaction between serotonin synthesis and mood may be 2-way, with serotonin influencing mood and mood influencing serotonin. Obviously, more work is needed to answer questions in this area. For example, is the improvement in mood associated with psychotherapy accompanied by increases in serotonin synthesis? If more precise information is obtained about the mental states that increase serotonin synthesis, will this help to enhance therapy techniques?
Exposure to bright light is a second possible approach to increasing serotonin without drugs. Bright light is, of course, a standard treatment for seasonal depression, but a few studies also suggest that it is an effective treatment for nonseasonal depression38 and also reduces depressed mood in women with premenstrual dysphoric disorder39 and in pregnant women suffering from depression.40 The evidence relating these effects to serotonin is indirect. In human postmortem brain, serotonin levels are higher in those who died in summer than in those who died in winter.41 A similar conclusion came from a study on healthy volunteers, in which serotonin synthesis was assessed by measurements of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the venous outflow from the brain.42 There was also a positive correlation between serotonin synthesis and the hours of sunlight on the day the measurements were made, independent of season. In rats, serotonin is highest during the light part of the light–dark cycle, and this state is driven by the photic cycle rather than the circadian rhythm.43,44 The existence of a retinoraphe tract may help explain why, in experimental animals, neuronal firing rates, c-fos expression and the serotonin content in the raphe nuclei are responsive to retinal light exposure.44–48 In humans, there is certainly an interaction between bright light and the serotonin system. The mood-lowering effect of acute tryptophan depletion in healthy women is completely blocked by carrying out the study in bright light (3000 lux) instead of dim light.49
Relatively few generations ago, most of the world population was involved in agriculture and was outdoors for much of the day. This would have resulted in high levels of bright light exposure even in winter. Even on a cloudy day, the light outside can be greater than 1000 lux, a level never normally achieved indoors. In a recent study carried out at around latitude 45° N, daily exposure to light greater than 1000 lux averaged about 30 minutes in winter and only about 90 minutes in summer50 among people working at least 30 hours weekly; weekends were included. In this group, summer bright light exposure was probably considerably less than the winter exposure of our agricultural ancestors. We may be living in a bright light–deprived society. A large literature that is beyond the scope of this editorial exists on the beneficial effect of bright light exposure in healthy individuals. Lamps designed for the treatment of seasonal affective disorder, which provide more lux than is ever achieved by normal indoor lighting, are readily available, although incorporating their use into a daily routine may be a challenge for some. However, other strategies, both personal and institutional, exist. “Light cafes” pioneered in Scandinavia have come to the United Kingdom,51 and an Austrian village that receives no sunshine in the winter because of its surrounding mountains is building a series of giant mirrors to reflect sunlight into the valley.52 Better use of daylight in buildings is an issue that architects are increasingly aware of. Working indoors does not have to be associated with suboptimal exposure to bright light.
A third strategy that may raise brain serotonin is exercise. A comprehensive review of the relation between exercise and mood concluded that antidepressant and anxiolytic effects have been clearly demonstrated.53 In the United Kingdom the National Institute for Health and Clinical Excellence, which works on behalf of the National Health Service and makes recommendations on treatments according to the best available evidence, has published a guide on the treatment of depression.54 The guide recommends treating mild clinical depression with various strategies, including exercise rather than antidepressants, because the risk–benefit ratio is poor for antidepressant use in patients with mild depression. Exercise improves mood in subclinical populations as well as in patients. The most consistent effect is seen when regular exercisers undertake aerobic exercise at a level with which they are familiar.53 However, some skepticism remains about the antidepressant effect of exercise, and the National Institute of Mental Health in the United States is currently funding a clinical trial of the antidepressant effect of exercise that is designed to overcome sources of potential bias and threats to internal and external validity that have limited previous research.55
Several lines of research suggest that exercise increases brain serotonin function in the human brain. Post and colleagues56 measured biogenic amine metabolites in cerebrospinal fluid (CSF) of patients with depression before and after they increased their physical activity to simulate mania. Physical activity increased 5-HIAA, but it is not clear that this was due to increased serotonin turnover or to mixing of CSF from higher regions, which contain higher levels of 5-HIAA, with lumbar CSF (or to a combination of both mechanisms). Nonetheless, this finding stimulated many animal studies on the effects of exercise. For example, Chaouloff and colleagues57 showed that exercise increased tryptophan and 5-HIAA in rat ventricles. More recent studies using intracerebral dialysis have shown that exercise increases extracellular serotonin and 5-HIAA in various brain areas, including the hippocampus and cortex (for example, see58–60). Two different mechanisms may be involved in this effect. As reviewed by Jacobs and Fornal,61 motor activity increases the firing rates of serotonin neurons, and this results in increased release and synthesis of serotonin.62 In addition, there is an increase in the brain of the serotonin precursor tryptophan that persists after exercise.63
The largest body of work in humans looking at the effect of exercise on tryptophan availability to the brain is concerned with the hypothesis that fatigue during exercise is associated with elevated brain tryptophan and serotonin synthesis. A large body of evidence supports the idea that exercise, including exercise to fatigue, is associated with an increase in plasma tryptophan and a decrease in the plasma level of the branched chain amino acids (BCAAs) leucine, isoleucine and valine (see64,65 for reviews). The BCAAs inhibit tryptophan transport into the brain.66 Because of the increase in plasma tryptophan and decrease in BCAA, there is a substantial increase in tryptophan availability to the brain. Tryptophan is an effective mild hypnotic,67 a fact that stimulated the hypothesis that it may be involved in fatigue. A full discussion of this topic is not within the scope of this editorial; however, it is notable that several clinical trials of BCAA investigated whether it was possible to counter fatigue by lowering brain tryptophan, with results that provided little support for the hypothesis. Further, exercise results in an increase in the plasma ratio of tryptophan to the BCAAs before the onset of fatigue.64,65 The conclusion of these studies is that, in humans, a rise in precursor availability should increase serotonin synthesis during and after exercise and that this is not related to fatigue, although it may be related to improved mood. Whether motor activity increases the firing rate of serotonin neurons in humans, as in animals, is not known. However, it is clear that aerobic exercise can improve mood.
As with exposure to bright light, there has been a large change in the level of vigorous physical exercise experienced since humans were hunter-gatherers or engaged primarily in agriculture.68 Lambert68 argued that the decline in vigorous physical exercise and, in particular, in effort-based rewards may contribute to the high level of depression in today’s society. The effect of exercise on serotonin suggests that the exercise itself, not the rewards that stem from exercise, may be important. If trials of exercise to prevent depression are successful, then prevention of depression can be added to the numerous other benefits of exercise.
The fourth factor that could play a role in raising brain serotonin is diet. According to some evidence, tryptophan, which increases brain serotonin in humans as in experimental animals,69 is an effective antidepressant in mild-to-moderate depression.67,70 Further, in healthy people with high trait irritability, it increases agreeableness, decreases quarrelsomeness and improves mood.34 However, whether tryptophan should be considered primarily as a drug or a dietary component is a matter of some dispute. In the United States, it is classified as a dietary component, but Canada and some European countries classify it as a drug. Treating tryptophan as a drug is reasonable because, first, there is normally no situation in which purified tryptophan is needed for dietary reasons, and second, purified tryptophan and foods containing tryptophan have different effects on brain serotonin. Although purified tryptophan increases brain serotonin, foods containing tryptophan do not.71 This is because tryptophan is transported into the brain by a transport system that is active toward all the large neutral amino acids and tryptophan is the least abundant amino acid in protein. There is competition between the various amino acids for the transport system, so after the ingestion of a meal containing protein, the rise in the plasma level of the other large neutral amino acids will prevent the rise in plasma tryptophan from increasing brain tryptophan. The idea, common in popular culture, that a high-protein food such as turkey will raise brain tryptophan and serotonin is, unfortunately, false. Another popular myth that is widespread on the Internet is that bananas improve mood because of their serotonin content. Although it is true that bananas contain serotonin, it does not cross the blood–brain barrier.
α-Lactalbumin, a minor constituent of milk, is one protein that contains relatively more tryptophan than most proteins. Acute ingestion of α-lactalbumin by humans can improve mood and cognition in some circumstances, presumably owing to increased serotonin.72,73 Enhancing the tryptophan content of the diet chronically with α-lactalbumin is probably not practical. However, increasing the tryptophan content of the diet relative to that of the other amino acids is something that possibly occurred in the past and could occur again in the future. Kerem and colleagues74 studied the tryptophan content of both wild chickpeas and the domesticated chickpeas that were bred from them in the Near East in neolithic times. The mean protein content (per mg dry seed) was similar for 73 cultivars and 15 wild varieties. In the cultivated group, however, the tryptophan content was almost twice that of the wild seeds. Interestingly, the greater part of the increase was due to an increase in the free tryptophan content (i.e., not part of the protein). In cultivated chickpeas, almost two-thirds of the tryptophan was in the free form. Kerem and colleagues74 argue that there was probably selection for seeds with a higher tryptophan content. This is plausible, given another example of an early strategy to increase the available tryptophan content of an important food source. Pellagra is a disorder caused by niacin deficiency, usually owing to poverty and a diet relying heavily on corn (maize), which has a low level of niacin and its precursor tryptophan. Cultures in the Americas that relied greatly on corn used alkali during its processing (e.g., boiling the corn in lime when making tortillas). This enhanced the nutritional quality of the corn by increasing the bioavailability of both niacin and tryptophan, a practice that prevented pellagra.75 The Europeans transported corn around the world but did not transport the traditional alkali-processing methods, thereby causing epidemics of pellagra in past centuries. Breeding corn with a higher tryptophan content was shown in the 1980s to prevent pellagra76; presumably, it also raised brain serotonin. In a recent issue of Nature Biotechnology, Morris and Sands77 argue that plant breeders should be focusing more on nutrition than on yield. They ask, “Could consumption of tryptophan-rich foods play a role in reducing the prevalence of depression and aggression in society?” Cross-national studies have reported a positive association between corn consumption and homicide rates78 and a negative association between dietary tryptophan and suicide rates.79 Although the idea behind such studies is interesting, any causal attribution must remain speculative, given the possible confounds. Nonetheless, the possibility that the mental health of a population could be improved by increasing the dietary intake of tryptophan relative to the dietary intake of other amino acids remains an interesting idea that should be explored.
The primary purpose of this editorial is to point out that pharmacologic strategies are not the only ones worthy of study when devising strategies to increase brain serotonin function. The effect of nonpharmacologic interventions on brain serotonin and the implications of increased serotonin for mood and behaviour need to be studied more. The amount of money and effort put into research on drugs that alter serotonin is very much greater than that put into non-pharmacologic methods. The magnitude of the discrepancy is probably neither in tune with the wishes of the public nor optimal for progress in the prevention and treatment of mental disorders.
Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in the central nervous system.
To View the Serotonin Molecule in 3D —>>in 3D with Jsmol
Chemical and Physical Properties of Serotonin
Serotonin is believed to play an important part of the biochemistry of depression, bipolar disorder and anxiety. It is also believed to be influential on sexuality.
Serotonin taken orally is not passed into the serotonin pathways of the brain. Since it is such an important regulating chemical, the blood-brain barrier prevents serotonin in the blood stream from directly affecting serotonin levels in the brain. However, the amino acid tryptophan and its metabolite 5-hydroxytryptophan — which serotonin is synthesized from — are capable of crossing the blood-brain barrier. These chemicals are readily available as dietary supplements and may be effective serotonergic agents.
Other ways of working around the blood-brain barrier include a variety of psychiatric medications that affect serotonin levels indirectly, including MAO inhibitors, and SSRIs which includes the well known antidepressant fluoxetine (trade name: Prozac®)
The MAO inhibitors prevent the breakdown of serotonin and therefore increase concentrations of the neurotransmitter in the brain. MAO inhibitors react negatively with many foods (which contain amines) and drugs and have a large list of side effects.
After serotonin is released by a neuron it activates receptors located on adjacent neurons. After activating these receptors serotonin is taken up by neurons, sometimes for reuse. More recent drugs inhibit the uptake of serotonin, again making it stay in the synapse longer. There are many classes of 5-HT receptors, all of which may be responsible for different things. These Selective Serotonin Re-uptake Inhibitors (SSRI) have fewer (though still numerous) side effects and fewer interactions with other drugs. Deficient (and sometimes, excessive) intake of various dietary minerals and vitamins can lead to disturbed levels of serotonin via disrupting either the production or reuptake processes.
Care must be taken in any attempt to increase serotonin levels, as a dangerous condition known as serotonin syndrome may result. This is especially a concern if multiple sertonergic drugs may interact. Serotonin is found extensively in the human gut, as well as in the blood stream.In our body, serotonin is synthesized from the amino acid tryptophan by various enzymes as shown in the formula below.
“Depression is a serious medical condition that may be due to a chemical imbalance, and Zoloft works to correct this imbalance.”
Ad for Zoloft
Herein Lies the Chemical Imbalance Myth
As one of only two countries in the world that permits direct to consumer advertising, you have undoubtedly been subjected to promotion of the “cause of depression.” A cause that is not your fault, but rather, a matter of too few little bubbles passing between the hubs in your brain! Don’t add that to your list of worries, though, because there is a convenient solution awaiting you at your doctor’s office.
What if I told you that, in six decades of research, the serotonin (or norepinephrine, or dopamine) theory of depression and anxiety has not achieved scientific credibility?
You’d want some supporting arguments for this shocking claim, so here you go:
The Science of Psychiatry?
Rather than some embarrassingly reductionist, one-deficiency-one-illness-one-pill model of mental illness, current exploration of human behavior has shown that we may know less than we ever thought we did. And that what we do know about root causes of mental illness seems to have more to do with the concept of evolutionary mismatch than with genes and chemical imbalances.
In fact, a meta-analysis of over 14,000 patients and Dr. Insel, head of the NIMH, had this to say:
“Despite high expectations, neither genomics nor imaging has yet impacted the diagnosis or treatment of the 45 million Americans with serious or moderate mental illness each year.”
To understand what imbalance is, we must know what balance looks like, and neuroscience, to date, has not characterized the optimal brain state, nor how to even assess for it. In a review of serotonin theories of depression, Andrews et al. turn the paradigm on its head and conclude:
We propose that depressed states are high serotonin phenomena, which challenges the prominent role the low serotonin hypothesis continues to have in depression research (Albert et al., 2012). We also propose that the direct serotonin-enhancing effects of antidepressants disturb energy homeostasis and worsen symptoms. We argue that symptom reduction, which only occurs over chronic treatment, is attributable to the compensatory responses of the brain attempting to restore energy homeostasis.
In this paper, they work to deconstruct our indoctrination around serotonin as a “happy chemical,” and clarify its complex role in redirecting energy production when a creature is under duress. It is only when we disturb the system with medication that the body’s response can sometimes result in a chemically adaptive state, that is temporary, at best (accounting for relapse rates, while on medication, of up to 60%). Even this analysis is a theoretical offering in the service of challenging the dominant paradigm.
A New England Journal of Medicine review on Major Depression, stated:
“…numerous studies of norepinephrine and serotonin metabolites in plasma, urine, and cerebrospinal fluid as well as postmortem studies of the brains of patients with depression, have yet to identify the purported deficiency reliably.”
The data has poked holes in the theory and even the field of psychiatry itself is putting down it’s sword. One of my favorite essays by Lacasse and Leo has compiled sentiments from influential thinkers in the field – mind you, these are conventional clinicians and researchers in mainstream practice – who have broken rank, casting doubt on what psychiatry has to offer around antidepressants:
Depression Is Not a Serotonin Deficiency
In the 1950s, reserpine, initially introduced to the US market as an anti-seizure medication, was noted to deplete brain serotonin stores in subjects, resulting in lethargy and sedation. These observations colluded with the clinical note that an anti-tuberculosis medication, iproniazid, invoked mood changes after five months of treatment in 70% of a 17 patient cohort. Finally, Dr. Joseph Schildkraut threw fairy dust on these mumbles and grumbles in 1965 with his hypothetical manifesto entitled “The Catecholamine Hypothesis of Affective Disorders” stating:
“At best, drug-induced affective disturbances can only be considered models of the natural disorders, while it remains to be demonstrated that the behavioral changes produced by these drugs have any relation to naturally occurring biochemical abnormalities which might be associated with the illness.”
A field struggling to establish biomedical legitimacy (beyond the therapeutic lobotomy!), psychiatry was ready for a rebranding, and the pharmaceutical industry was all too happy to partner in the effort.
Of course, the risk inherent in “working backwards” in this way (noting effects and presuming mechanisms) is that we tell ourselves that we have learned something about the body, when in fact, all we have learned is that patented, synthesized chemicals have effects on our behavior. This is referred to as the drug-based model by Dr. Joanna Moncrieff. In this model, we acknowledge that antidepressants have effects, but that these effects, in no way are curative or reparative.
Consider the woman with social phobia who finds that drinking two cocktails eases her symptoms. One could imagine, how, in a 6 week randomized trial, this “treatment” could be found to be successful and recommended for daily use and even prevention of symptoms. How her withdrawal symptoms after 10 years of daily compliance could lead those around her to believe that she “needed” the alcohol to correct an imbalance. This analogy is all too close to the truth.
No Intervention Creates Better Outcomes
Psychiatrist Dr. Daniel Carlat has said: “Where there is a scientific vacuum, drug companies are happy to insert a marketing message and call it science. As a result, psychiatry has become a proving ground for outrageous manipulations of science in the service of profit.”
So, what happens when we let drug companies tell doctors what science is? We have an industry and a profession working together to maintain a house of cards theory in the face of contradictory evidence.
We have a global situation in which increases in prescribing are resulting in increases in severity of illness (including numbers and length of episodes) relative to those who have never been treated with medication.
To truly appreciate the breadth of evidence that states antidepressants are ineffective and unsafe, we have to get behind the walls that the pharmaceutical companies erect. We have to unearth unpublished data, data that they were hoping to keep in the dusty catacombs.
A now famous 2008 study in the New England Journal of Medicine by Turner et al sought to expose the extent of this data manipulation. They demonstrated that, from 1987 to 2004, 12 antidepressants were approved based on 74 studies. Thirty-eight were positive, and 37 of these were published. Thirty-six were negative (showing no benefit), and 3 of these were published as such while 11 were published with a positive spin (always read the data not the author’s conclusion!), and 22 were unpublished.
In 1998 tour de force, Dr. Irving Kirsch, an expert on the placebo effect, published a meta–analysis of 3,000 patients who were treated with antidepressants, psychotherapy, placebo, or no treatment and found that only 27% of the therapeutic response was attributable to the drug’s action.
This was followed up by a 2008 review, which invoked the Freedom of Information Act to obtain access to unpublished studies, finding that, when these were included, antidepressants outperformed placebo in only 20 of 46 trials (less than half!), and that the overall difference between drugs and placebos was 1.7 points on the 52 point Hamilton Scale. This small increment is clinically insignificant, and likely accounted for by medication side effects strategically employed (sedation or activation).
When active placebos were used, the Cochrane database found that differences between drugs and placebos disappeared, supporting the assertion that inert placebos inflate perceived drug effects.
The finding of tremendous placebo effect in the treatment groups was also echoed in two different meta-analysis by Khan et al who found a 10% difference between placebo and antidepressant efficacy, and comparable suicide rates. The most recent trial examining the role of “expectancy” or belief in antidepressant effect, found that patients lost their perceived benefit if they believed that they might be getting a sugar pill even if they were continued on their formerly effective treatment dose of Prozac.
The largest, non-industry funded study, costing the public $35 million dollars, followed 4,000 patients treated with Celexa (not blinded, so they knew what they were getting), and found that half of them improved at 8 weeks. Those that didn’t were switched to Wellbutrin, Effexor, or Zoloft OR “augmented” with Buspar or Wellbutrin.
Guess what? It didn’t matter what was done, because they remitted at the same unimpressive rate of 18-30% regardless, with only 3% of patients in remission at 12 months.
How could it be that medications like Wellbutrin, which purportedly primarily disrupt dopamine signaling, and medications like Stablon, which theoretically enhances the reuptake of serotonin, both work to resolve this underlying imbalance? Why would thyroid, benzodiazepines, beta blockers, and opiates also “work”? And what does depression have in common with panic disorder, phobias, OCD, eating disorders, and social anxiety that all of these diagnoses would warrant the same exact chemical fix?
Are There Alternative Options?
As a holistic clinician, one of my biggest pet peeves is the use of amino acids and other nutraceuticals with “serotonin-boosting” claims. These integrative practitioners have taken a page from the allopathic playbook and are seeking to copy-cat what they perceive antidepressants to be doing.
The foundational “data” for the modern serotonin theory of mood utilizes tryptophan depletion methods which involve feeding volunteers amino acid mixtures without tryptophan and are rife with complicated interpretations.
Simply put, there has never been a study that demonstrates that this intervention causes mood changes in any patients who have not been treated with antidepressants.
In an important paper entitled Mechanism of acute tryptophan depletion: is it only serotonin?, van Donkelaar et al caution clinicians and researchers about the interpretation of tryptophan research. They clarify that there are many potential effects of this methodology, stating:
In general, several findings support the fact that depression may not be caused solely by an abnormality of 5-HT function, but more likely by a dysfunction of other systems or brain regions modulated by 5-HT or interacting with its dietary precursor. Similarly, the ATD method does not seem to challenge the 5-HT system per se, but rather triggers 5HT-mediated adverse events.
Andrews goes further to include this interpretation in a long list of arguments against the role of serotonin deficiency in depression (Box 1).
So if we cannot confirm the role of serotonin in mood and we have good reason to believe that antidepressant effect is largely based on belief, then why are we trying to “boost serotonin”?
Why Your Prescription Never Expires
All you have to do is spend a few minutes on survivingantidepressants.org or beyondmeds.com to appreciate that we have created a monster. Millions of men, women, and children, the world over are suffering, without clinical guidance (because this is NOT a part of medical training) to discontinue psychiatric meds. I have been humbled, as a clinician who seeks to help these patients, by what these medications are capable of. Psychotropic withdrawal can make alcohol and heroin detox look like a breeze.
An important analysis by the former director of the NIMH makes claims that antidepressants “create perturbations in neurotransmitter functions” causing the body to compensate through a series of adaptations which occur after “chronic administration” leading to brains that function, after a few weeks, in a way that is “qualitatively as well as quantitatively different from the normal state.”
Changes in beta-adrenergic receptor density, serotonin autoreceptor sensitivity, and serotonin turnover all struggle to compensate for the assault of the medication.
Andrews calls this “oppositional tolerance,” and demonstrates through a careful meta-analysis of 46 studies demonstrating that a patient’s risk of relapse is directly proportionate to how “perturbing” the medication is, and is always higher than placebo (44.6% vs 24.7%). They challenge the notion that findings of decreased relapse on continued medication represent anything other than drug-induced response to discontinuation of a substance to which the body has developed tolerance. They go a step further to add:
“For instance, in naturalistic studies, unmedicated patients have much shorter episodes, and better long-term prospects, than medicated patients. Several of these studies have found that the average duration of an untreated episode of major depression is 12–13 weeks.”
Harvard researchers also concluded that at least fifty percent of drug-withdrawn patients relapsed within 14 months. In fact:
Long-term antidepressant use may be depressogenic . . . it is possible that antidepressant agents modify the hardwiring of neuronal synapses (which) not only render antidepressants ineffective but also induce a resident, refractory depressive state.
So, when your doctor says, “You see, look how sick you are, you shouldn’t have stopped that medication,” you should know that the data suggests that your symptoms are withdrawal, not relapse.
Longitudinal studies demonstrate poor functional outcomes for those treated with 60% of patients still meeting diagnostic criteria at one year (despite transient improvement within the first 3 months). When baseline severity is controlled for, two prospective studies support a worse outcome in those prescribed medication:
One in which the never-medicated group experienced a 62% improvement by six months, whereas the drug-treated patients experienced only a 33% reduction in symptoms. Another WHO study of depressed patients in 15 cities found that, at the end of one year, those who weren’t exposed to psychotropic medications enjoyed much better “general health;” that their depressive symptoms were much milder;” and that they were less likely to still be “mentally ill.”
I’m not done yet.
In a retrospective 10-year study in the Netherlands, 76% of those with unmedicated depression recovered without relapse, relative to 50% of those treated.
Unlike the mess of contradictory studies around short-term effects, there are no comparable studies that show a better outcome in those prescribed antidepressants longterm.
First Do No Harm
So, we have a half-baked theory in a vacuum of science that that pharmaceutical industry raced to fill. We have the illusion of short-term efficacy and assumptions about long-term safety. But are these medications actually killing people?
The answer is yes.
Unequivocally, antidepressants cause suicidal and homicidal behavior. The Russian Roulette of patients vulnerable to these “side effects” is only beginning to be elucidated and may have something to do with genetic variants around metabolism of these chemicals. Dr. David Healy has worked tirelessly to expose the data that implicates antidepressants in suicidality and violence, maintaining a database for reporting, writing, and lecturing about cases of medication-induced death that could make your soul wince.
What about our most vulnerable?
I have countless patients in my practice who report new onset of suicidal ideation within weeks of starting an antidepressant. In a population where there are only 2 randomized trials, I have grave concerns about postpartum women who are treated with antidepressants before more benign and effective interventions such as dietary modification and thyroid treatment. Hold your heart as you read through these reports of women who took their own and their children’s’ lives while treated with medications.
Then there is the use of these medications in children as young as 2 years old. How did we ever get the idea that this was a safe and effective treatment for this demographic? Look no further than data like Study 329, which cost Glaxo Smith Klein 3 billion dollars for their efforts to promote antidepressants to children. These efforts required ghost-written and manipulated data that suppressed a signal of suicidality, falsely represented Paxil as outperforming placebo, and contributes to an irrepressible mountain of harm done to our children by the field of psychiatry.
RIP Chemical Imbalance Theory
As Moncrieff and Cohen so succinctly state:
Our analysis indicates that there are no specific antidepressant drugs, that most of the short-term effects of antidepressants are shared by many other drugs, and that long-term drug treatment with antidepressants or any other drugs has not been shown to lead to long-term elevation of mood. We suggest that the term “antidepressant” should be abandoned.
So, where do we turn?
The field of psychoneuroimmunology dominates the research as an iconic example of how medicine must surpass its own simplistic boundaries if we are going to begin to chip away at the some 50% of Americans who will struggle with mood symptoms, and 11% of whom will be medicated for it.
There are times in our evolution as a cultural species that we need to unlearn what we think we know. We have to move out of the comfort of certainty and into the freeing light of uncertainty. It is from this space of acknowledged unknowing that we can truly grow. From my vantage point, this growth will encompass a sense of wonder – both a curiosity about what symptoms of mental illness may be telling us about our physiology and spirit, as well as a sense of humbled awe at all that we do not yet have the tools to appreciate. For this reason, honoring our co-evolution with the natural world, and sending the body a signal of safety through movement, diet, meditation, and environmental detoxification represents our most primal and most powerful tool for healing.