Healing Mental Disorders
Author: Jian Gao, PhD
Editor: Mr. Frederick Malphurs
July 4, 2023
Mounting evidence leads to an inescapable conclusion: the greatest tragedy in medicine is how patients with mental disorders have been treated in the last 100 years – symptoms are pushed under the rug, root causes are ignored, and severe side effects and sometime irreversible damage from the treatments endure.
Unfortunately, about 1 in 5 Americans suffer some type of mental health condition — the cost of treating mental health conditions reached $225 billion in 2019, a 52% increase since 2009.1 Mental Illnesses, such as depression, autism, ADHD, bipolar, schizophrenia, PTSD, and dementia, can often inflict more pain and suffering on loved ones and society than on the patients themselves. The gravity of the problem is well reflected by the escalation of the suicide rate and gun violence.
Why do so many suffer from mental disorders, and why are the treatments ineffective and even counterproductive? To get to the bottom of the problem, this article, starting with the dark history of psychiatry and how the mentally ill have been treated, explicates the root causes which have been largely ignored by the establishment and explains the proper treatments that can heal the mental disorders such as depression, bipolar, and schizophrenia (substance abuse is a separate subject and not discussed in this article).
To understand the gist of the problem, it is instructive to see mental disorders as a spectrum rather than discrete categories such as major-depressive disorder, bipolar disorder, and schizophrenia — biologists and psychiatrists have been unable to find any genetic or neuroscientific evidence to put patients into separate categories. And most importantly, successful treatments hinge on effective management of the root causes, and most if not all the mental disorders, regardless of how different the manifestations appear, are induced by the same root causes; more precisely, by different combinations/interactions of the same root causes as will be explained.
This article does not pretend to provide or promise magic pills — there have been and there will be no magic pills for mental disorders. The only way to heal mental disorders is to address the root causes. And this article is intended to help you do that.
1. The Dark History of Treating the Mentally Ill
The brutality towards mentally ill patients is systematically documented by Robert Whitaker, an award-winning journalist, in his well-researched book Mad in America,2 a must-read if you are interested in the history of psychiatry.
The first hospital for the insane was opened in Philadelphia in 1756, where unruly patients were regularly whipped and chained to rings of iron. “The lunatics also had to suffer the indignity of serving as a public spectacle. After the hospital opened, visiting the mad had quickly become a popular Sunday outing, similar to visiting a zoo… in 1762, the hospital, trying to make the best of an unfortunate situation, began charging a visit’s fee of four pence.”2
In the ensuing years, ‘medical treatments’ for the mad were developed, but they were nothing short of torture — physically weakening them by bleeding, inducing nausea, starving, etc. In the European countries, spinning chairs, beds, stools, and even waterboarding (simulation of drowning) became the mainstream treatments to ‘cure’ the madness.
After a half century of suffering in the hands of keepers and doctors, the mentally ill saw their turn of fortune. In England, Quakers, rooted in their religious belief, brought about a long overdue reform in treating the mentally ill. Across the Atlantic, in 1817, Quakers opened the first moral-treatment asylum in Philadelphia, and soon others followed suit in different cities. These asylums were built to heal rather than jail patients – serving no more than 250 patients, the yards were filled with flowerbeds and gardens. Patients were treated with kindness – no more whipping, their complaints were listened to, and their time was filled with activities such as tending plants, playing games rather than loneliness in locked cells. The outcomes of moral treatments were remarkable: asylums saw more than 50% of their patients recovered and discharged.2
Unfortunately, the moral treatment movement became the victim of its own success. The number of asylums or mental health hospitals mushroomed from 18 in 1840 to 139 in 1880. And the size of the asylums, especially those owned by states, was getting larger too; some of them were housing over 1,000 patients. Then, soaring expenditures became a big problem. To cut cost, states tended to hire asylum superintendents who could make the budget rather than take care of the patients. And gardens, reading rooms, and recreational programs were all gone. Worse still, liberal use of restraints and brute force to maintain order returned. Of course, poor outcomes and thus bad reputations followed.
Then, “Neurologists delivered the final below [to the moral treatment movement]. The Civil War, with its tremendous number of casualties, had helped produce this new medical specialty… touting their experience in nervous disorders,” wrote Whitaker.2 “But without the war sending the wounded their way, they hungered for patients, and the crowded asylum presented an obvious solution.” Believing in themselves to be well-schooled in hard sciences such as anatomy and physiology, neurologists leading the charge publicly belittled asylum doctors or psychiatrists as inept gardeners and farmers who knew nothing about diagnosis, pathology, and treatment of mental illness.
The turf war went on for three years; in the end, neurologists failed to win – psychiatrists remained in charge of the state asylums.3 The real casualty of the war was the moral treatment of the insane, which became a thing of the past.
Facing attacks from neurologists and the resulting distrust from the public, psychiatrists were eager to reinvent themselves as ‘medical’ doctors. So, a string of new treatments was created. For instance, hydrotherapy and steam cabinet treatment (keeping patients in hot tubs or steam cabinet for hours and even days on end) became popular in the early 20 century. Other treatments such as removing body parts like the uterus, ovaries, teeth, and colon were also in vogue and claimed to be effective in more than 50% of the patients. In fairness, some of these treatments have some merits; for instance, steam cabinet treatment can help detoxification.
Of course, these treatments were not effective for majority of the patients. So, psychiatrists went on to devise the most horrifying shock ‘therapies’ that for sure ‘worked’ for everybody. The first such a treatment was the insulin-coma therapy pioneered by Austrian psychiatrist Manfred Sakel while working in Berlin in the late 1920s. The therapy puts patients into coma by injecting large doses of insulin which pulls sugar out of the blood stream and thus deprives the brain of fuel it needs. Sakel reported the therapy was not really effective unless it was repeatedly administered.
In the following years, the therapy gained popularity both in Europe and America — “Insulin coma therapy was eagerly embraced by the psychiatric profession in the mid-twentieth century and promoted by leading psychiatrists of the time.”4 The therapy was widely claimed by the psychiatrists to have a cure rate of over 70 percent and was accoladed as medical wonder by major magazines and newspapers like Time and The New York Times.
In reality, the therapy, putting patients into a coma approximately 30 consecutive days apart from Sundays, did nothing other than kill brain cells, causing permanent brain damage, and reducing patients to naïve toddlers.2,4 Yet the therapy was continued to be used until the early 1960s.
As if insulin coma therapy were not barbaric enough, Metrazol convulsive therapy also gained wide acceptance for being cheaper and much easier to administer, especially compared to insulin coma therapy which was expensive and labor intensive. By 1939, 70 percent of the American mental hospitals used it on their patients. The therapy used pentylenetetrazol (trade name Metrazol, a synthetic drug, more accurately, a poison) to induce violent seizures which often caused loosened teeth, tore muscles, broke bones, and even fractured spines. It also caused internal bleeding in vital organs such as kidneys, lungs, and the brain.
Because of the uncertainty about proper dosing, patients had to wait for the seizure to come on as Metrazol was slowly injected. As a result, patients felt being roasted alive in an oven and their brain exploded – patients and others saw the treatment as being worse than torture. Like Insulin coma therapy, Metrazol convulsive therapy had to be administered multiple times to be ‘effective.’ So, doctors and nurses had to chase the patients around the room to get them to take Metrazol. Sadly, the therapy was not only used on schizophrenia but also for depressive patients.
By 1941, electroshock therapy invented by Italian psychiatrist Ugo Cerletti started to replace Metrazol convulsive therapy as a more desired alternative to induce seizures in the American mental hospitals. For electroshock therapy, the electrodes are placed on the patients’ temple and a burst of electricity is sent from one side of the brain to the other in order to induce seizures and convulsions. At the time, the electricity voltage could reach 110 volts for some patients, and patients were shocked three times weekly. The reality is the electroshock therapy did nothing but cause permanent brain damage and memory loss. In addition, up to 40 percent of the patients undergoing the electroshock suffered bone fractures resulting from the violent convulsions.2
Yet, the worst was yet to come. In 1935, based on some evidence showing “chimpanzee with both frontal lobes removed became more cooperative and willing to accomplish tasks, while displaying no frustration” presented by two Yale psychiatrists/physiologists, Carlyle Jacobsen and John Fulton, at the Second International Congress of Neurology in London in 1935, Portuguese doctor António Egas Moniz developed the procedure later called lobotomy to ‘cure’ mental disorders by drilling holes into the patients’ heads and then using alcohol or surgical tools such as wires or ice pick-like instruments to destroy their frontal lobes. On November 12, 1935, Moniz performed his first lobotomy on a 63-year-old woman suffering from depression, anxiety, paranoia, hallucinations, and insomnia. The surgery was proclaimed a big success, and soon American doctors followed.
The treatment in reality was no better than amputating legs to cure knee arthritis. Yet, the creation of the procedure earned Moniz the Nobel Prize — the Nobel Committee described the procedure as one of the most important discoveries ever made in psychiatric medicine.5
The lobotomy procedure continued to be performed not only on patients with schizophrenia but also those with depression until the 1960s when antipsychotic drugs were accepted as alternative treatments.
As a side note, unlike lobotomy, electroshock therapy has not been completely abandoned — the modified or improved version called electroconvulsive therapy (ECT) is still used to treat some patients with disorders such as severe depression and schizophrenia. The greatest improvement is that during the procedure, patients are under general anesthesia and the muscles are relaxed; as a result, the seizures and physical convulsions are not felt by the patients or visible to others. Although nobody knows how and why it works, some patients do report temporary improvement after treatments. Certainly, ECT does not fix the root causes, but it may provide a transitory relief for individuals with irreversible damage in the brain where neurons cannot work orderly. As science advances, more targeted ECT such as deep brain stimulation (DBS) may render temporal relief for some patients with certain symptoms. For instance, NY Times recently (November 8, 2022) reported DBS improved binge eating for two patients in a pilot study. But, again, none of these procedures address the root causes.
2. The Era of New Antipsychotics and Antidepressants
The first antipsychotic drug chlorpromazine (brand name: Thorazine) was introduced into the US in 1954 by Smith, Kline & French (founded in 1891 in Philadelphia PA and ceased operation in 1989) and it is still in use today. Many believe the introduction of chlorpromazine revolutionized psychiatric care.
Chlorpromazine belongs to a class of chemicals called phenothiazines initially used as synthetic dyes and insecticides. Chlorpromazine was first synthesized in 1951 by Paul Charpentier, in the laboratories of Rhône-Poulenc, a French pharmaceutical company. It was initially intended as a potentiator of general anesthesia. For its apparent tranquillizing effects, on January 19, 1952, chlorpromazine was used the first time to treat a severely agitated psychotic 24-year-old patient in a military hospital in Paris. After 20 days of treatment with chlorpromazine (50 mg intravenously each day), the patient was reportedly ready to “resume normal life.”6 The positive result was reported on February 22, 1952, at a meeting of the Société Médico-Psychologique in Paris, and then a paper was published in the March 1952 issue of the Annales Médico-Psychologiques.
The report and publication generated great interest in chlorpromazine – more patients were treated with it and nearly a dozen papers were published in the same year. So, a new and revolutionary drug was born – in November 1952, chlorpromazine became available as a prescription drug under the proprietary name Largactil (meaning large in action). Within three years, the use of chlorpromazine in psychiatry spread across the world.
In the US, chlorpromazine use was approved by the FDA on March 26, 1954. Immediately, Smith, Kline & French mounted an all-out marketing campaign to sell the new drug. It was an instant success – chlorpromazine was hailed as a wonder drug or a miracle pill by major magazines and newspapers such as Time and The New York Times.
What does chlorpromazine do to the patients? A 1954 study praising the drug published in the Journal of American Medical Association said it all: “In the present study, it was observed that, when given parenterally and in sufficient dose to psychotic or severely obsessive patients, the drug produced an effect similar to frontal lobotomy. Patients who had been severely agitated, anxious, and belligerent became immobile, wax-like, quiet, relaxed, and emotionally indifferent; unlike persons who have received barbiturates for sedation they remained responsive when spoken to and could easily be awakened if they fell asleep.”
Chlorpromazine therapy is indeed chemical lobotomy as believed by many – it blunts severe psychotic symptoms, but at the same time it also wipes out the patients’ inner identity and intelligence which have little chance coming back.
Nevertheless, chlorpromazine set the standard for others to emulate. More than a dozen other similar antipsychotic drugs like haloperidol and loxapine were developed and put on the market before the atypical drugs came in the 1990s. As a side note, all psychotic drugs developed during the 1950s-1980s are called typical drugs because they have the same typical side effects as lobotomy caused: emotional blunting, akathisia (feeling restless like you can’t sit still, and have the urge to tap your fingers or jiggle your legs), dystonia (muscles contract involuntarily which can be painful), Parkinsonism (symptoms are similar to Parkinson’s disease), tardive dyskinesia (involuntary facial movements such as sucking or chewing motion with your mouth, sticking out your tongue, or blinking your eyes constantly), and a whole host of other problems such as arrhythmia, blindness, and fatal blood clotting. These drugs are also called neuroleptics or first-generation antipsychotic drugs.
Despite their wide use, the mechanisms of action of neuroleptics were unknown. It was only later discovered that neuroleptics work by blocking dopamine D2 receptors in the brain. This discovery led to the hypothesis that the root cause of psychiatric symptoms is too much dopamine in the brain. To the contrary, there is still no evidence this hypothesis is true.
The atypical or second-generation antipsychotic drugs were introduced to the market in the 1990s. Rather than only blocking dopamine D2 receptors as the first generation drugs do, the second-generation antipsychotics block both dopamine and serotonin receptors.7 Despite being astronomically more expensive, studies after studies have shown the second generation drugs are no more effective than the first generation.8-12 Many believe the development of second-generation antipsychotic drugs was driven by greed. By the early 1980s, the patents of the leading neuroleptics like chlorpromazine and haloperidol had expired and their prices were driven down by the genetic versions — chlorpromazine was priced for less than $10 per month, and haloperidol did not fare better either.2
In fairness, second-generation antipsychotics (SGAs) cause fewer typical symptoms such as emotional detachment and involuntarily body movement associated with the first-generation antipsychotics. But there is a catch — SGAs have been shown to be associated with adverse metabolic side-effects such as weight gain, type 2 diabetes, hypertension, and dyslipidemia [abnormally elevated cholesterol]. As a result, some believe “the reduction in neurological side effects was more than offset by adverse metabolic effects.”8
It appears Newton’s Third Law of Motion applies in human body’s biology too: “For every action, there is an equal and opposite reaction.”
The use of these drugs is not limited to those suffering from schizophrenia or psychosis. Both first and second-generation antipsychotics have also been used off-label in other neuropsychiatric conditions such as attention-deficit hyperactivity disorder (ADHD), generalized anxiety disorder, obsessive-compulsive disorder, depression, insomnia, post-traumatic stress disorder (PTSD), personality disorders, eating disorders, substance use and dependence disorders, geriatric agitation, and behavioral disturbances in dementia.13
On top of the serious and often irreversible side effects, how effective are these antipsychotics? As well documented in the book Mad in America by Whitaker,2 and the book Unhinged by Danial Carlat,14 MD, renowned psychiatrist, Chair of the Department of Psychiatry and medical director of inpatient psychiatry at MelroseWakefield Healthcare, the effectiveness of these drugs is hit-and-miss – they work for some patients but not others, and/or may work for a while and then stop working.
Studies indeed have shown antipsychotics only help for about half of patients with positive symptoms (e.g., hallucinations and delusions),15 but do nothing or even worsen negative symptoms (e.g., withdrawal and vacated emotions).
Antidepressants are even worse. An international research team from the UK, US, and Canada analyzed all the randomized controlled trials submitted to the FDA and found the new-generation antidepressants were no better than placebo (sugar pills) for those patients with moderate or severe depression. And for the most severely depressed patients, the antidepressants seemed to work, but actually this seemingly positive effect was due to the waning responsiveness to placebo.16
How is it possible that antidepressants are no better than sugar pills given they are approved by the FDA and so many people are taking them (according to CDC, “During 2015–2018, 13.2% of Americans aged 18 and over reported taking antidepressant medication in the past 30 days.”). Unfortunately, the ineffectiveness is an inescapable fact. “What the published studies really indicate is that most of the improvement shown by depressed people when they take antidepressants is due to the placebo effect,” explained Dr. Irving Kirsch, an internationally recognized psychologist and mental health researcher, in his science-based and truth-seeking book The Emperor’s New Drugs – Exploring the Antidepressant Myth. “Depression is not caused by a chemical imbalance in the brain, and it is not cured by medication.”
If it is still not clear, the state of mental health care is capsulized well by Thomas Insel, when leaving his position as Director of the NIMH (National Institute of Mental Health): “I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that I realize that while I think I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs — I think $20 billion — I don’t think we moved the needle in reducing suicide, reducing hospitalizations, improving recovery for the tens of millions of people who have mental illness.”17
Sadly, to a large extent, the state of mental health care is driven by greed. Although the wellbeing of the patients did not get better, the bottom line did for big pharma and “the people who write textbooks and medical-journal papers, issue practice guidelines (treatment recommendations), sit on FDA and other governmental advisory panels, head professional societies, and speak at the innumerable meetings and dinners that take place every day to teach clinicians about prescription drugs.”18
“Consider three examples I’ve written about before: first, in a survey of 200 expert panels that issued practice guidelines, one third of the panel members acknowledged that they had some financial interest in the drugs they assessed. Second, in 2004, after the NIH National Cholesterol Education Program called for sharply lowering the acceptable levels of “bad” cholesterol, it was revealed that eight of nine members of the panel writing the recommendations had financial ties to the makers of cholesterol-lowering drugs. Third, of the 170 contributors to the most recent edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 95 had financial ties to drug companies, including all of the contributors to the sections on mood disorders and schizophrenia,” added Dr. Marcia Angell, MD, former editor of the top medical journal the New England Journal of Medicine, an true and rare insider of the corrupted medical system who is willing to speaking out for the interest of the public. “Perhaps most important, many members of the eighteen standing committees of experts that advise the FDA on drug approvals also have financial ties to the industry.”18
It is given that “drug companies—like other investor-owned businesses—are charged with increasing the value of their shareholders’ stock. That is their fiduciary responsibility, and they would be remiss if they didn’t uphold it. All their other activities are means to that end.”18 But those big-name high-flying medical experts who are doctors sworn to do no harm should know better.
3. The Root Causes of Mental Disorders
No drugs treating mental disorders can be really effective and safe unless they fix the root causes. Yet, no drugs on the market since the 1950s are intended to do so. They were developed to block or suppress brain functions, or alter brain chemistry, which is much like using a sledgehammer to right a clock.
What causes mental disorders? For decades, the public and even many doctors have been misled to believe imbalance or abnormal brain chemistry is the culprit and antipsychotics and antidepressants are the solution. Ironically, there is no evidence indicating patients with schizophrenia have too much dopamine or serotonin in the brain despite all the antipsychotics designed to shut down their activities,19-21 and on the other hand, there is no evidence showing depressive patients have too little serotonin in their brain despite antidepressants being intended to make it more active.22
It is entirely conceivable some chemicals like dopamine or serotonin in the brain of those with severe mental disorders are out of balance, but that is most likely a symptom rather than the root cause. What causes the chemical imbalance in the first place?
The root causes of mental disorders can be complex but are not intractable or unfixable. Regardless of what type of disorders, depression or dementia, or anything in between, scientifically, the root causes are either psychological or biological, and in most cases, the combination of the two ranging from mostly psychological to mostly biological.
Psychological Causes
Myriad psychological factors, such as adverse childhood experiences, challenges in school, family strife, financial difficulties, traumatic events, loss of loved ones, social isolation, hostile working environment, all can contribute to mental disorders. For the purpose of conveying the key concepts, all these factors can be loosely referred to as stress or stressors (the event or experience causing stress). For those whose disorders are mainly caused by stress, psychotherapy is the right treatment — its effectiveness has passed the test of time. Recall the moral treatment, a prototype of the modern psychotherapy, reportedly had a success rate of over 50 percent in the 1800s.2
Psychotherapy is equally effective today. However, it has been underappreciated and underused as described by Dr. Carlat in his book Unhinged,14 a must-read offering a front-row view inside psychiatry practice and research for anybody interested in mental health care. “In fact, according to the latest data from a group of researchers at Columbia University, only one out of every ten psychiatrists offer therapy to all their patients. Doing psychotherapy doesn’t pay well enough. I can see three or four patients per hour if I focus on medications (such psychiatrists are called ‘psychopharmacologists’), but only one patient in that time period if I do therapy,” wrote Dr. Carlat. “The income differential is a powerful incentive to drop therapy from our repertoire of skills, and psychiatrists have generally followed the money.”
Even if psychotherapy were not underused, we should understand stress (in a broad sense) is only one of the triggers and therefore psychotherapy does not help those patients whose symptoms are primarily driven by biological risk factors. The ineffectiveness of psychotherapy to those patients creates an opening for big pharma and interest groups to sell the chemical imbalance theory and expensive drugs. Unfortunately, none of the drugs like antipsychotics and antidepressants fix the biological risk factors either.
Biological Causes
Although the number of potential biological risks or causes can be overwhelming, they can be viewed as genetic or environmental.
Genetic Factors
Genes have become the scapegoat for very single disease when there is ‘no cure’ and there is no exception for mental disorders — it is easier to blame the genes, hide behind the veil of ‘genetic predisposition,’ and to prescribe mind-altering drugs than to fix the real problems.
Although it is convenient to blame the genes for the ills, no meaningful associations between DNA polymorphisms (genetic mutations) and psychiatric disorders have been identified except for ApoE4 associated with Alzheimer’s disease as will be further discussed shortly. Just a few years ago, however, the hopeless quest of the genetic crystal ball was seemingly revived by the so called GWASs (genome-wide association studies) that produced GPSs (genome-wide polygenic scores) by combining hundreds, thousands, and even millions of SNPs (single nucleotide polymorphism) when no relationship can be found with single SNPs.
Now GPS has become the hottest subject in the genetic universe. As a result, “Psychiatric Genetics Begins to Find Its Footing.”23 However, the practice is no more than just data dredging – it has little practical value, as described by a scathing editorial entitled “Polygenic scores: Are they a public health hazard?” published in 2019: “GPSs are a ‘fortune-telling’ device, and indeed they are, in the same sense as are astrology and tea leaves. GPSs are the ultimate ‘snake oil’ based on measuring noise: some of the most expensive snake oil in human history.”24
The GPSs in psychiatry don’t even pass the laugh test. According to the CDC, in only 20 years from 2000 to 2020, autism prevalence skyrocketed 417 percent from 1 in 150 to 1 in 36 children.25 Have the genes of these children changed? Researchers from Johns Hopkins University find the prevalence of major depressive episodes among adolescents jumped 30% during the decade from 1995 to 2014.26 And according to CDC, in 16 years from 2000 through 2016, the age-adjusted suicide rate increased by 30%; in particular, for females, the rate increased by 50% during the same time period.27 Have the genes, especially women’s, changed?
It cannot be clearer that mental disorders, like most other chronic diseases, are a result of the changing environment, which is increasingly inundated with toxic chemicals, rather than the fault of genes. Granted, some people are more prone to mental disorders than others because of genetic variations. But bear in mind, except for rare genetic mutations, the vast majority of the mutations or SNPs are normal and even indispensable – without variation, there’d be no evolution – humankind could be wiped out by one virus or plague if everyone had identical genes.
Genes are not wrongdoers — they are the victims of the changing environment too as detailed in Chapter 10 of the book Road to Health. So, let’s focus on the environment factors we can change rather than on the genes, through no fault of their own, that we cannot change. Of course, in the future, science may advance enough to identify rare mutations in related psychiatric disorders and edit them and may also be able to edit the genes to accommodate the changing environment and personal lifestyles. But for the patients who are suffering now, it is more like a pie in the sky than anything else.
Environmental Factors
Environmental factors can affect our health from inside and outside our body.
Internal Triggers
From inside, dysbiosis (overgrowth of pathogenic bacteria in the gut) and intestinal permeability (leaky gut) are the most dangerous enemies.
The fact that gut bacteria can induce mental disorders was recognized at least a century ago by George Porter Phillips in the London’s notorious Bethlem Royal Hospital housing the mental ill. “Of the 18 patients Phillips tested [altering gut bacteria], 11 were cured completely, with two others showing significant improvement – offering some of the first evidence that our gut bacteria can have a profound influence over our mental wellbeing.”28
Treating infection to cure psychiatric disorders was practiced in America too. In the largest mental hospital of the nation at the time, the New Jersey State Hospital in Trenton, Dr. Henry Cotton, the medical director of the hospital, and his staff performed surgeries on thousands of patients to remove the “infected body parts” such as colon and teeth to cure psychiatric disorders like psychosis and depression.29 The practice came to an end in the early 1930s after Cotton and his staff got caught falsifying data on outcomes (inflating effective rate and underreporting mortality rate). Cotton fell from grace and unfortunately the concept of dysbiosis was also buried with his notoriety for nearly 80 years.
Not until a little over a decade ago, was the concept and gravity of dysbiosis re-recognized by alternative medicine practitioners. Nowadays, testing and treating gut dysbiosis is common practice among alternative medicine practitioners such as Functional Medicine doctors. Research activities on this topic has also surged. According to National Library of Medicine, there were only 10 research papers on the topic (gut microbiota and psychiatric disorders) published in 2011; it jumped to 655 in 2022. Some of the papers appeared in the top science journals such as Cell.30
How can gut microbiota (more specifically, bacteria) affect our mental status? Well, like any other organisms, bacteria need to eat and poop. It turns out what they produce is vital to our health. In fact, good bacteria produce many compounds (metabolites), such as vitamins and SCFAs (acetic acid, propionic acid, butyric acid, hexanoic acid, pentanoic acid, isovaleric acid, and isobutyric acid), all of which affect our wellbeing. Furthermore, they also produce neurotransmitters, which regulate brain activities. For example, Lactobacilli and Bifidobacteria produce GABA, Escherichia coli produce dopamine and serotonin, and Lactobacilli produce acetylcholine.30 In fact, over 90% of the body’s serotonin is produced in the gut which is widely called the second brain.
On the other hand, bad bacteria secrete neurotoxins and pro-inflammatory compounds such as lipopolysaccharide (LPS), enterotoxins, microbial-derived amyloids, and small non-coding RNA (sncRNA), which can severely damage the brain.31
In addition, bad bacteria also produce other compounds like LPS glycolipid subtype (BF-LPS) and B. fragilis toxin (BFT) disrupting the linings of intestines as well as the blood-brain barrier (BBB) and thus inducing leaky gut and leaky brain, which permit neurotoxins entering the systemic circulation and gaining access into the brain.31
Indeed, gut dysbiosis and leaky gut are co-conspirators down there. So, for starters, what is leaky gut? Inside our belly, there is an extensive intestinal lining covering more than 4,000 square feet of surface area, which forms a tight barrier controlling what gets absorbed into the bloodstream. Leaky gut, also called intestinal permeability, happens when the intestinal lining is damaged or dysfunctional, allowing bacteria, toxins, and large food particles pass through to reach the blood stream. Numerous risk factors such as stress, gluten, NSAIDs (non-steroidal anti-inflammatory drugs), and bacterial metabolites, can trigger leaky gut. And some of them can also damage the blood-brain barrier and induce leaky brain.
Leaky gut and leaky brain together constitute an expressway for all kinds of neurotoxins to reach the brain – a recipe for mental disorders.
Taken together, what happens in the gut does not stay in the gut – it goes to the brain. Indeed, mounting evidence indicates dysbiosis and leaky gut are linked to all mental disorders from depression to autism, and from schizophrenia to dementia.32-49 Of course, dysbiosis and leaky gut are not the only root causes.
In addition to gut dysbiosis, anybody having acute psychiatric symptoms should also have other infections checked out too. Infectious agents like bacteria and viruses have been suspected to cause psychiatric disorders such as schizophrenia since the late 1800s based on the observation that individuals sometimes present with symptoms of schizophrenia, bipolar disorder or depression shortly after having an infectious disease.
For the last two decades or so, the infectious theory of psychosis has received renewed scientific support – numerous studies have linked the disorder to certain infections caused, for example, by a parasite called toxoplasma gondii or by a virus called cytomegalovirus.50 Of course, at the patient level, it is difficult to determine how much the infection contributes to the psychiatric condition – it could be unrelated, it could be one of the contributing factors, or it could be the chief culprit. Nevertheless, infection causing psychiatric disorders is not farfetched, which is well illustrated by a 2005 case report published in Clinical Practice and Epidemiology in Mental Health. In the abstract, the authors summarized:51
We describe a 22 year-old female Caucasian who, three days after a mild pharyngitis [sore throat], developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation.
Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles’ lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids.
More recently, the fact that viral infections can trigger mental disorders is further highlighted by the COVID-19 pandemic which leaves some long COVID patients with conditions such as brain fog, depression, and anxiety. Granted, other factors may play a role too, but there is a takeaway message here – mental disorders are not necessarily indicating there’s something mysteriously and hopelessly wrong in the head.
External Triggers
The escalating number of people suffering from mental disorders such as depression and autism in the last few decades leads to an inescapable conclusion: environmental toxins are one of the key drivers behind the rise – nothing else has changed that much. Indeed, an increasing number of studies have demonstrated thousands of manmade chemicals in the environment are linked to psychiatric disorders like depression and autism. Many of these chemicals, such as pesticides in our food chain, ubiquitous POPs (persistent organic pollutants) like the notorious PCBs, and VOCs (volatile organic compounds emitted as poisonous gases from almost all synthetic products in our homes), are neurotoxic – poisoning the brain and causing variety of mental disorders such autism, depression, and schizophrenia.52-57
Furthermore, although the general public is largely unaware, mounting research evidence indicates these synthetic chemicals, especially those thousands of endocrine disrupters such as BPA, PCBs, DES, and pesticides, can affect sexual behaviors or preferences.58-63 Studies have clearly demonstrated these chemicals can even alter sexual organs during the early development period.64-66 Although scientific experiments in these cases cannot be performed on humans, the increasing number of children born with intersex variation (ambiguous sex organs or a combination of male and female) should serve as a canary in the coal mine.67
In addition to manmade chemicals, heavy metals such as lead and mercury released by variety of industries have increasingly contaminated the air, water, and food chain. And it has been well established these heavy metals can do serious damage to the brain and induce a host of psychiatric disorders.68-70
These countless and ubiquitous chemicals and heavy metals should be taken seriously by anybody with any mental disorders – the detoxification capacity (ability of getting these toxins out of the body) is different from person to person thanks to genetic variants (SNPs). On top of SNPs, epigenetics (gene expression) may play an even larger role in detoxification because it dictates the synthesis of enzymes used to move the toxins out of the body. And gene expression can be greatly altered by what we eat and even how we think.71,72 The book Road to Health (chapter 10) provides more details on this topic.
Another important external contributor to mental health is nutrition – “we are what we eat” is not only true for our body but also for our mind. Indeed, what we eat can profoundly affect our mental status through multiple passways in addition to gene expression. In 2015, a group of 17 international experts on behalf of The International Society for Nutritional Psychiatry Research concluded “the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology.”73 In fact, numerous studies including randomized controlled trials have demonstrated micronutrients play a significant role in mental health, especially for major depression.74-81
The vital role of nutrition in mental health is apparent – “the human brain operates at a very high metabolic rate and uses a substantial proportion of total energy and nutrient intake; in both structure and function (including intracellular and intercellular communication), it is reliant on amino acids, fats, vitamins, and minerals or trace elements.”73
Among all the micronutrients, the importance of vitamin D in mental health cannot be overstated. Research has revealed vitamin D, now widely regarded as a neurosteroid, regulates brain development and affects brain functions – gestational or neonatal vitamin D deficiency is associated with a high risk of psychiatric disorders like autism, and schizophrenia;82 and vitamin D deficiency has been linked to some degenerative conditions such as Alzheimer’s. Most commonly, vitamin D deficiency is a major contributor to depression.83-85 In fact, it is hard to find a disease, mental or physical, that is not related to vitamin D deficiency. Vitamin D deficiency is one of the easiest things in life to fix, yet many are still deficient and unaware of it.
In addition to vitamin D, vitamin Bs, especially B9 (folate) and B12, also play a significant role in brain function and mental health.86-89 For instance, folate is metabolized into L-methylfolate which is able to cross the blood brain barrier (BBB) and regulates the production of three major neurotransmitters, dopamine, norepinephrine, and serotonin.90,91 Further, studies have also shown vitamin C plays a vital role in psychiatric disorders including depression, anxiety and schizophrenia as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease.92-94
Although all the 20 or so essential minerals are vital to our mental as well as physical health,95-97 zinc has been studied more than others. Numerous studies have shown zinc deficiency is common among mental health patients and zinc supplements help to ameliorate psychiatric symptoms.98-101
Apart from vitamins and minerals, omega-3s (omega-3 fatty acids) are also essential for our brain to work properly. Omega-3s play a significant role in mental health throughout early childhood and even into adulthood. In the brain, Omega-3s are important for cellular membrane fluidity, function, neurotransmitter synthesis, release, re-uptake, and signal transduction.102,103 Research has also revealed omega-3s, mainly EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), can activate Nrf2-directed gene expression which ramps up antioxidant and detox activities protecting brain cells.104,105 Regardless of the mechanisms, numerous studies have shown inadequate consumption of omega-3s increases the risk of numerous mental health disorders such as ADHD, autism, bipolar disorder, depression, as well as schizophrenia. And dietary supplementation of omega-3s improves the symptoms of these conditions.106-110
Another important group of nutrients are polyphenols, which are compounds naturally found in plant foods including vegetables, fruits, spices, herbs, and tea. At least 8,000 different polyphenols have been identified thus far, which can be grouped into 4 main categories: flavonoids, phenolic acids, polyphenolic amides, and others.111 In addition to their beneficial effects on physical health, studies have shown polyphenols protect the brain by preventing neurodegeneration, inhibiting neuroinflammation, and reducing age-related cognitive decline.112-116 The health benefits of polyphenols have been believed to be their antioxidant effects, but the truth is science has not advanced enough to tease out the true mechanisms of action.
Nevertheless, more and more studies have demonstrated the benefits of high consumption of polyphenols to psychiatric disorders like depression and ADHD.117-121
Related to nutrition and diet, another external trigger, food sensitivity (mostly gluten sensitivity or intolerance) has increasingly garnered attention of alternative medicine practitioners and researchers. Although the prevalence of gluten-triggered psychiatric disorders is unknown because the mainstream psychiatry refuses to recognize the problem and the public is largely aware of it, mounting evidence indicates it is not uncommon. Growing number of studies have shown gluten sensitivity can trigger variety of psychiatric disorders such as ADHD, autism, depression, bipolar, and psychosis.122-133 Numerous cases are reported by practicing psychiatrists and neurologists in books and by researchers in medical journals, where removing gluten from diets reversed the psychiatric disorders such as ADHD, schizophrenia, depression, as well as autism, and the symptoms reappeared whenever exposed to gluten again.134-138
In short, food sensitivity as an environmental trigger cannot be overlooked when hunting the root causes of mental disorders.
4. Healing Mental Disorders by Treating the Root Causes
Mental disorders can be healed so long as the root causes are fixed. In many cases, the fix can be easy – for example, depression is lifted by just taking vitamin D supplements.139 However, for most cases, the fix is not always that simple because very often multiple causes are behind the disorders like depression and autism. Identifying and addressing the invisible root causes can be challenging, but you can do it if you are willing to make the effort.
First, genes are not destiny. There is no depression gene and there is no autism gene. Certainly, genetic variations can put some individuals at higher risk of mental disorders than others. What it means is some people are more sensitive than others to the root causes such as stress and chemical toxins. For instance, those with null GSTM1 and GSTT1 which encode detoxification enzymes are at higher risk of variety of health issues because of the decreased capacity in removing toxins out of the body. However, GSTM1 and GSTT1 null are not a problem if you are mindful to avoid harmful chemicals.
Taken together, it comes down to this: we cannot change our genes, but we can change how we deal with environmental factors affecting our genes and mental health.
Second, psychiatric disorders like schizophrenia and bipolar are not a result of a dark and mysterious force seizing the soul of a person. We must understand mental disorders do not necessarily have their root causes in the head. Yes, chronic severe stress (in a broad sense) or negative thinking can by itself cause depression and other mental disorders by inducing dysbiosis, affecting the nervous and endocrinal systems, and altering gene expression which manages the production of all the hormones and enzymes, etc. But very often stress is not the sole or even main cause of the problem. More likely than not, stress is the last straw bringing the camel down after your brain has been assaulted by toxins produced by the pathogenic bacteria in the gut, the thousands of chemicals in the environment, and poor nutrition.
However, you can’t expect the camel will get up and run after taking off the last straw that brought it down. You can’t heal mental disorders by addressing one trigger at a time – all potential triggers must be addressed simultaneously. Diseases are just like a semitruck, once in motion, it does not take much power to stay in motion and it is hard to stop.
For many, it is also easy to fall into a trap of believing negative thinking is the chief culprit of mental disorders and antidepressants or antipsychotics are the solution. Of course, stress and negative thinking can trigger psychiatric disorders, but the other way around is also true – it is hard for anybody with mental disorders such as depression to think positively. To break the vicious feedback loop, it is paramount to address stress or negative thinking and environmental factors all together.
Finally, in most cases, it is impossible to know the exact root causes — very likely the condition is a result of multiple causes colluding together. Along with other triggers, our body is exposed to thousands of manmade chemicals that can trigger or contribute to mental disorders; how can you know what to fix? Too often patients or care givers are overwhelmed and give up; as a result, the disorders become chronic or incurable.
It does not have to be that way. When you feel overwhelmed and lost, remind yourself there are only four things you need to manage: (1) stress, (2) gut, (3) the environment toxins (including food sensitivity), and (4) nutrition. There is no reason not to take action to heal yourself or your loved ones.
Remember, when you can’t see your enemies firing at you from the thick brush, your rifle probably does not help much even if you are a sharpshooter. You need to bring your machinegun out. If that does not work, throw a firebomb at them.
Healing mental disorders is not wishful thinking or an academic theory. In real life, countless people get themselves out of depression and other serious mental disorders by addressing the root causes rather than relying on prescription drugs. Even autism, sealed as irreversible by the medical establishment, can be healed too.
It is enlightening to meet Jason, a patient of Dr. David Perlmutter, MD, an expert on nutrition, food sensitivity, gut flora (dysbiosis) and brain disorders. At age 3, Jason could only speak single words, and developed obsessions with repetitive things such as flipping light switches and moving his hands. Over the years, his parents took him to multiple doctors who ordered numerous tests like EEG, MRI, and blood work, none of which were helpful of course. At age 12, his parents took Jason to Dr. David Perlmutter. After a few months of treatment for dysbiosis plus some supplements such as vitamin D, Jason became a vibrant normal kid (see Jason’s video on Dr. Perlmutter’s website).
Dr. Perlmutter is no charlatan or snake oil salesman. He is a traditionally trained MD and board-certified neurologist and serves on the Board of Directors and is a Fellow of the American College of Nutrition. He has published extensively in peer-reviewed scientific journals and serves as a member of the Editorial Board for the Journal of Alzheimer’s Disease. He is a five-time New York Times bestselling author. And he has been on many nationally syndicated television programs including 20/20, the Today Show, Oprah, Larry King Live, CNN, Fox News, Fox and Friends, the Dr. Oz Show, the CBS Early Show, and CBS This Morning.
Healing or reversing autism is not a rare or miracle event. Just look at the website of the Autism Community in Action to see how many kids have recovered from autism.
To reverse autism, the most important step for parents is first to ditch the dogma of no cure. Granted, healing autism is not always easy – everything depends if the root causes are identified and addressed. Therefore, parents’ perseverance is a must. In this regard, actress Jenny McCarthy is a role model. Her son, Evan, was diagnosed with autism at age two and half. Evan’s autism was so severe that he was locked into his own dark place and had little communication with the outside world including his parents – could not talk, make eye contact, let alone make friends. And he kept having terrifying seizures.
His heroic mom Jenny refused to give up and fought against the medical establishment to pull her son out of the dark place he was in. She became a ‘Google scholar’ and started her most torturous and rewarding journey. After putting her son on a strict gluten-free and casein-free diet, added dietary supplements, and later eliminated candida, Jenny extricated her son from the ‘black hole’. Now Evan is has become YouTube sensational – running his own YouTube channel called “Gaming USA” with one of his friends.
Jenny’s fight to pull her son back was much more challenging than a paragraph can describe. Her journey was well documented in her heart-felt book, Louder than Words – A Mother’s Journey in Healing Autism. All parents having an autistic child should read the book – very inspiring. A short version of her journey is also documented by PBS Frontline.140
Another disheartening condition, schizophrenia/psychosis, is also widely believed incurable. That is not true either. As reported in a well-respected journal Nutrients, a 14-year-old Italian girl completely recovered from psychosis after being put on gluten free diet within a week (google and read the report – it’s free).141 Other cases completely reversed by staying on a gluten free diet have been reported in medical journals too.142 Note that these cases were reported in peer reviewed scientific journals, not sales pitches from charlatans or quacks.
Of course, a gluten free diet won’t heal everybody with autism or schizophrenia – gluten sensitivity is only one of many factors which can induce psychiatric disorders. The key is to address the root causes, which are often not in the head.
If you still doubt these horrific mental disorders can be cured or reversed once the root causes are identified and managed, please read the book Brain on Fire (also made into a movie) by Susannah Cahalan, a journalist with the New York Post – she became ill and was diagnosed with bipolar, psychosis, schizophrenia and nearly locked into a long-term psychiatric institution, which could have been a death sentence. Thank heaven, at the last moment, a bright out-of-box thinking physician figured out the root cause – her psychic symptoms were induced by an autoimmune condition. After the treatment of her autoimmunity, Susannah has recovered completely and returned to her work. To date, sadly, delayed diagnosis or misdiagnosis of this condition is still common.143,144
Finally, many consider Alzheimer’s disease to be scarier than cancer because it is believed not only incurable but also untreatable. Thank heaven, the notion of no cure and no hope is cracking. Again, the key is to understand the root causes as described by those who have recovered from Alzheimer’s disease in the book, The First Survivors of Alzheimer’s, by Dale Bredesen, MD, a neurologist and pioneer in reversing neurodegenerative diseases. More encouragingly, some of those recovered from Alzheimer’s carry the ApoE4 gene, the strongest genetic risk factor for Alzheimer’s disease. In any event, it should be noted most ApoE4 carriers do not get Alzheimer’s (about 1 in 4 people carry the gene), and about half of the patients with Alzheimer’s carry the gene.145 Once again: genes are not destiny.
* * *
All in all, this article is trying to drive one thing home: for most if not all mental disorders, the root cause is not some kind of dark and mysterious force in the head, it is not chemical imbalance in the brain, and it is not the genes. For all psychiatric disorders, regardless of how different the symptoms appear, the culprit(s) are most likely lying in four areas: stress (in a broad sense), gut (dysbiosis and leaky gut), environmental toxins (including food sensitivity and infections), and nutrition (especially micronutrients).
Most often, the disorder is a result of multiple triggers from the four areas. Bear in mind, stress or negative thinking is rarely the sole or principal cause of depression or other mental disorders; rather, it is more likely the last straw bringing the camel down. To reverse mental disorders like depression and schizophrenia, all root causes need to be addressed at the same time. You can’t expect the camel will get up and run after removing the last straw that brought it down — the disorder will likely linger even if one of the triggers is missed.
Identifying and addressing the root causes can be challenging, when you feel lost and discouraged, remind yourself the culprits can only be in the four areas. And if your rifle can’t hit the target, use your shotgun, or throw a grenade at the invisible instigators. Most importantly, take action to address the root causes as early as possible before real damage is done to the brain – you can heal the disease, but you may not be able to reverse the damage done by it.
Finally, it is important to understand fixing the root causes may take time and in many cases prescription drugs can help reduce acute symptoms associated with the wellbeing and safety of the patients and others. However, for depression, patients and caregivers or loved ones need to know antidepressants are little better than sugar pills but have a plethora of side effects.146,147 In particular, studies have shown antidepressants use is linked to suicidality and violence.148-152 If you are looking for an alternative to antidepressants, St. John’s wort merits a try — three systematic reviews analyzed up to 35 of randomized controlled trials have consistently found St. John’s wort is as effective as antidepressants for mild and moderate depression with few side effects.153-155 Lately, other treatment options such as magical mushrooms (psilocybin) and marijuana are increasingly available for patients to relieve certain symptoms such as depression and anxiety.156,157 But the efficacy and side effects of long-term use are unknow. Bear in mind, mental disorders are not due to deficiency of St. John’s wort, magical mushrooms, or marijuana in the brain.
Taken all together, the three most important things to heal mental disorders are: (1) identify the root causes, (2) address the root causes, and (3) stay away from the root causes.
About the Author and Editor: Jian Gao, PhD, is a healthcare analyst/researcher for the last 25 years who devoted his analytical skills to understanding health sciences and clinical evidence. Mr. Frederick Malphurs is a retired senior healthcare executive in charge of multiple hospitals for decades who dedicated his entire 37 years’ career to improving patient care. Neither of us takes pleasure in criticizing any individuals, groups, or organizations for the failed state of healthcare, but we share a common passion — to reduce unnecessary sufferings inflicted by the so-called chronic or incurable diseases on patients and their loved ones by analyzing and sharing information on root causes, effective treatments, and prevention.
Disclaimer: This article and any contents on this website are informational or educational only and should by no means be considered as a substitute for the advice of a qualified medical professional. It is the patients and caregivers’ solemn responsibility to work with qualified professionals to develop the best treatment plan. The author and editor assume no liability of any outcomes from any treatments or interventions.
References
- Leonhardt M. What you need to know about the cost and accessibility of mental health care in America. May 2021. https://www.cnbc.com/2021/05/10/cost-and-accessibility-of-mental-health-care-in-america.html.
- Whitaker R. Mad in America. Bad Science, Bad Medicine, and the Enduring Mistreatment of the Mentally Ill. Basic Books. Hachette Book Group. 1290 Avenue of the Americas, New York, NY 10114.
- Torrey EF. The Year Neurology Almost Took Over Psychiatry. Psychiatric Times. Jan. 1, 2002; Vol 19 No 1. https://www.psychiatrictimes.com/view/year-neurology-almost-took-over-psychiatry
- Freudenthal R, Moncrieff J. ‘A landmark in psychiatric progress’? The role of evidence in the rise and fall of insulin coma therapy. Hist Psychiatry. 2022 Mar;33(1):65-78.
- Tan SY, Yip A. António Egas Moniz (1874-1955): Lobotomy pioneer and Nobel laureate. Singapore Med J. 2014 Apr;55(4):175-6.
- Ban TA. Fifty years chlorpromazine: a historical perspective. Neuropsychiatr Dis Treat. 2007 Aug;3(4):495-500.
- Chokhawala K, Stevens L. Antipsychotic Medications. [Updated 2022 Mar 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519503/
- Rosenheck R. Second generation antipsychotics: evolution of scientific knowledge or uncovering fraud. Epidemiol Psychiatr Sci. 2013 Sep;22(3):235-7.
- Cheng F, Jones PB. Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design. Epidemiol Psychiatr Sci. 2013 Sep;22(3):223-33.
- Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31-41.
- Abou-Setta AM, Mousavi SS, Spooner C, et al. First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Aug. (Comparative Effectiveness Reviews, No. 63.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK107254/
- Hartling L, Abou-Setta AM, Dursun S, et al. Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis. Ann Intern Med. 2012 Oct 2;157(7):498-511.
- Ameer MA, Saadabadi A. Neuroleptic Medications. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459150/
- Carlat DJ. Unhinged. The Trouble with Psychiatry – A Doctor’s Revelations about a Profession in Crisis. Free Press. 2010. 1230 Ave of the Americans. New York, NY 10020.
- Stepnicki P, Kondej M, Kaczor AA. Current Concepts and Treatments of Schizophrenia. Molecules. 2018 Aug 20;23(8):2087. doi: 10.3390/molecules23082087. PMID: 30127324; PMCID: PMC6222385.
- Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008 Feb;5(2):e45. doi: 10.1371/journal.pmed.0050045. PMID: 18303940; PMCID: PMC2253608.
- https://www.wired.com/2017/05/star-neuroscientist-tom-insel-leaves-google-spawned-verily-startup/#:~:text=It%20was%20a%20tough%20decision,scratch%20it%20at%20some%20point.%E2%80%9D
- Big Pharma, Bad Medicine – Boston Review
- Moncrieff J. A critique of the dopamine hypothesis of schizophrenia and psychosis. Harv Rev Psychiatry. 2009;17(3):214-25.
- Stępnicki P, Kondej M, Kaczor AA. Current Concepts and Treatments of Schizophrenia. Molecules. 2018 Aug 20;23(8):2087. doi: 10.3390/molecules23082087. PMID: 30127324; PMCID: PMC6222385.
- Seeman MV. History of the dopamine hypothesis of antipsychotic action. World J Psychiatry. 2021 Jul 19;11(7):355-364.
- Moncrieff J, Cooper RE, Stockmann T, et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2022 Jul 20. doi: 10.1038/s41380-022-01661-0. Epub ahead of print. PMID: 35854107.
- Smoller JW. Psychiatric Genetics Begins to Find Its Footing. Am J Psychiatry. 2019 Aug 1;176(8):609-614.
- Baverstock K. Polygenic scores: Are they a public health hazard? Prog Biophys Mol Biol. 2019 Dec;149:4-8.
- CDC: Data & Statistics. https://www.cdc.gov/ncbddd/autism/data.html.
- Mojtabai R, Olfson M, Han B. National Trends in the Prevalence and Treatment of Depression in Adolescents and Young Adults. Pediatrics, 2016; DOI: 10.1542/peds.2016-1878.
- Suicide Rates in the United States Continue to Increase. https://www.cdc.gov/nchs/products/databriefs/db309.htm#:~:text=From%202000%20through%202016%2C%20the,2000%20to%2021.4%20in%202016.
- https://www.bbc.com/future/article/20190218-how-the-bacteria-inside-you-could-affect-your-mental-health
- Andrew Scull A. Madhouse: A Tragic Tale of Megalomania and Modern Medicine. Yale University Press. 2005.
- Sonali S, Ray B, Ahmed Tousif H, et al. Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review. Cells. 2022 Apr 16;11(8):1362. doi: 10.3390/cells11081362. PMID: 35456041; PMCID: PMC9030021.
- Lukiw WJ. Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins-Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain. Front Cell Infect Microbiol. 2020 Feb 12;10:22. doi: 10.3389/fcimb.2020.00022. PMID: 32117799; PMCID: PMC7028696.
- Fond G, Boukouaci W, Chevalier G, et al. The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review. Pathol Biol (Paris). 2015 Feb;63(1):35-42.
- Rogers GB, Keating DJ, Young RL, et al. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016 Jun;21(6):738-48.
- Clapp M, Aurora N, Herrera L, et al. Gut microbiota’s effect on mental health: The gut-brain axis. Clin Pract. 2017 Sep 15;7(4):987. doi: 10.4081/cp.2017.987. PMID: 29071061; PMCID: PMC5641835.
- Fattorusso A, Di Genova L, Dell’Isola GB, et al. Autism Spectrum Disorders and the Gut Microbiota. Nutrients. 2019 Feb 28;11(3):521. doi: 10.3390/nu11030521. PMID: 30823414; PMCID: PMC6471505.
- Megur A, Baltriukienė D, Bukelskienė V, Burokas A. The Microbiota-Gut-Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame? Nutrients. 2020 Dec 24;13(1):37. doi: 10.3390/nu13010037. PMID: 33374235; PMCID: PMC7824474.
- Capuco A, Urits I, Hasoon J, et al. Current Perspectives on Gut Microbiome Dysbiosis and Depression. Adv Ther. 2020 Apr;37(4):1328-1346.
- Chen LL, Abbaspour A, Mkoma GF, et al. Gut Microbiota in Psychiatric Disorders: A Systematic Review. Psychosom Med. 2021 Sep 1;83(7):679-692.
- Munawar N, Ahsan K, Muhammad K, et al. Hidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics? Int J Mol Sci. 2021 Jul 18;22(14):7671. doi: 10.3390/ijms22147671.
- Safadi JM, Quinton AMG, Lennox BR, et al. Gut dysbiosis in severe mental illness and chronic fatigue: a novel trans-diagnostic construct? A systematic review and meta-analysis. Mol Psychiatry. 2022 Jan;27(1):141-153.
- Szeligowski T, Yun AL, Lennox BR, Burnet PWJ. The Gut Microbiome and Schizophrenia: The Current State of the Field and Clinical Applications. Front Psychiatry. 2020 Mar 12;11:156. doi: 10.3389/fpsyt.2020.00156.
- Obrenovich MEM. Leaky Gut, Leaky Brain? Microorganisms. 2018 Oct 18;6(4):107. doi: 10.3390/microorganisms6040107.
- Morris G, Fernandes BS, Puri BK, et al. Leaky brain in neurological and psychiatric disorders: Drivers and consequences. Aust N Z J Psychiatry. 2018 Oct;52(10):924-948.
- Julio-Pieper M, Bravo JA, Aliaga E, et al. Review article: Intestinal barrier dysfunction and central nervous system disorders–a controversial association. Aliment Pharmacol Ther. 2014;40(10):1187-201.
- Maes M, Sirivichayakul S, Kanchanatawan B, Vodjani A. Breakdown of the Paracellular Tight and Adherens Junctions in the Gut and Blood Brain Barrier and Damage to the Vascular Barrier in Patients with Deficit Schizophrenia. Neurotox Res. 2019 Aug;36(2):306-322.
- Ishida I, Ogura J, Aizawa E, et al. Gut permeability and its clinical relevance in schizophrenia. Neuropsychopharmacol Rep. 2022 Mar;42(1):70-76.
- Ohlsson L, Gustafsson A, Lavant E, et al. Leaky gut biomarkers in depression and suicidal behavior. Acta Psychiatr Scand. 2019 Feb;139(2):185-193.
- Simeonova D, Ivanovska M, Murdjeva M, et al. Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays. Curr Top Med Chem. 2018;18(19):1641-1655.
- Doney E, Cadoret A, Dion-Albert L, et al. Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders. Eur J Neurosci. 2022 May;55(9-10):2851-2894.
- Yolken RH, Torrey EF. Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol Psychiatry. 2008 May;13(5):470-9.
- Xavier M, Correa B, Coromina M, Canas N, Guimarães J. Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection. Clin Pract Epidemiol Ment Health. 2005 Sep 15;1:15. doi: 10.1186/1745-0179-1-15.
- Reuben A, Manczak EM, Cabrera LY, et al. The Interplay of Environmental Exposures and Mental Health: Setting an Agenda. Environ Health Perspect. 2022 Feb;130(2):25001. doi: 10.1289/EHP9889.
- Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017 Mar 17;8:13. doi: 10.1186/s13229-017-0121-4.
- Guo Z, Xie HQ, Zhang P, et al. Dioxins as potential risk factors for autism spectrum disorder. Environ Int. 2018 Dec;121(Pt 1):906-915.
- van den Bosch M, Meyer-Lindenberg A. Environmental Exposures and Depression: Biological Mechanisms and Epidemiological Evidence. Annu Rev Public Health. 2019 Apr 1;40:239-259.
- Khan A, Plana-Ripoll O, Antonsen S, et al. Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark. PLoS Biol. 2019 Aug 20;17(8):e3000353. doi: 10.1371/journal.pbio.3000353.
- Burkett JP, Miller GW. 2021. Using the exposome to understand environmental contributors to psychiatric disorders. Neuropsychopharmacology 46(1):263–264.
- Hood E. Are EDCs blurring issues of gender? Environ Health Perspect. 2005 Oct;113(10):A670-7. doi: 10.1289/ehp.113-a670.
- Yurekli BS, Kutbay NO, Saygili F. An endocrine disrupting chemical, bisphenol A: could it be associated with sex differentiation in brain regarding to transsexuality? Endocrine Abstracts (2015) 37 EP208 | DOI: 10.1530/endoabs.37.EP208.
- Mhaouty-Kodja S, Naulé L, Capela D. Sexual Behavior: From Hormonal Regulation to Endocrine Disruption. Neuroendocrinology. 2018;107(4):400-416.
- Gore AC, Holley AM, Crews D. Mate choice, sexual selection, and endocrine-disrupting chemicals. Horm Behav. 2018 May;101:3–12.
- Varticovski L, Stavreva DA, McGowan A, et al. Endocrine disruptors of sex hormone activities. Mol Cell Endocrinol. 2022 Jan 1;539:111415. doi: 10.1016/j.mce.2021.111415. Epub 2021 Jul 30.
- Palanza P, Paterlini S, Brambilla MM, et al. Sex-biased impact of endocrine disrupting chemicals on behavioral development and vulnerability to disease: Of mice and children. Neurosci Biobehav Rev. 2021 Feb;121:29-46.
- Hormone Disruptors Linked To Genital Changes and Sexual Preference. https://www.loe.org/shows/segments.html?programID=11-P13-00001&segmentID=7
- O’Laughlin LN. Troubling Figures: Endocrine Disruptors, Intersex Frogs, and the Logics of Environmental Science. Catalyst: Feminism, Theory, Technoscience. 2020, Volume6(Issue1). https://catalystjournal.org/index.php/catalyst/article/view/32350
- Patisaul HB. REPRODUCTIVE TOXICOLOGY: Endocrine disruption and reproductive disorders: impacts on sexually dimorphic neuroendocrine pathways. Reproduction. 2021 Oct 5;162(5):F111-F130.
- Rich AL, Phipps LM, Tiwari S, et al. The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals. Environ Health Insights. 2016 Sep 8;10:163-71.
- Bose-O’Reilly S, McCarty KM, Steckling N, Lettmeier B. Mercury exposure and children’s health. Curr Probl Pediatr Adolesc Health Care. 2010 Sep;40(8):186-215.
- Reuben A, Schaefer JD, Moffitt TE, et al. Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health. JAMA Psychiatry. 2019 Apr 1;76(4):418-425.
- Schwaba T, Bleidorn W, Hopwood CJ, et al. The impact of childhood lead exposure on adult personality: Evidence from the United States, Europe, and a large-scale natural experiment. Proc Natl Acad Sci U S A. 2021 Jul 20;118(29):e2020104118. doi: 10.1073/pnas.2020104118.
- Stevens AJ, Rucklidge JJ, Kennedy MA. Epigenetics, nutrition and mental health. Is there a relationship? Nutr Neurosci. 2018 Nov;21(9):602-613.
- Bainomugisa C, Mehta D. Chapter 8 – How stress affects gene expression through epigenetic modifications,Editor(s): Nagy A. Youssef, In Translational Epigenetics, Epigenetics of Stress and Stress Disorders, Academic Press,Volume 31, 2022, Pages 99-118, ISBN 9780128230398, https://doi.org/10.1016/B978-0-12-823039-8.00014-9.
- Sarris J, Logan AC, Akbaraly, et al; International Society for Nutritional Psychiatry Research. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015 Mar;2(3):271-4.
- Blampied M, Bell C, Gilbert C, Rucklidge JJ. Broad spectrum micronutrient formulas for the treatment of symptoms of depression, stress, and/or anxiety: a systematic review. Expert Rev Neurother. 2020 Apr;20(4):351-371.
- Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med. 2013 Feb;75(2):144-53.
- Marx W, Moseley G, Berk M, Jacka F. Nutritional psychiatry: the present state of the evidence. Proc Nutr Soc. 2017 Nov;76(4):427-436.
- Grosso G. Nutritional Psychiatry: How Diet Affects Brain through Gut Microbiota. Nutrients. 2021 Apr 14;13(4):1282. doi: 10.3390/nu13041282.
- Loughman A, Staudacher HM, Rocks T, et al. Diet and Mental Health. Mod Trends Psychiatry. 2021;32:100-112.
- Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 2017 Jan 30;15(1):23. doi: 10.1186/s12916-017-0791-y.
- Parletta N, Zarnowiecki D, Cho J, et al. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci. 2019 Jul;22(7):474-487.
- Firth J, Marx W, Dash S, et al. The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials. Psychosom Med. 2019 Apr;81(3):265-280.
- Eyles DW. Vitamin D: Brain and Behavior. JBMR Plus. 2020 Oct 18;5(1):e10419. doi: 10.1002/jbm4.10419.
- Głąbska D, Kołota A, Lachowicz K, et al. The Influence of Vitamin D Intake and Status on Mental Health in Children: A Systematic Review. Nutrients. 2021 Mar 16;13(3):952. doi: 10.3390/nu13030952.
- Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Feb;202:100-7.
- Kaviani M, Nikooyeh B, Zand H, Yaghmaei P, Neyestani TR. Effects of vitamin D supplementation on depression and some involved neurotransmitters. J Affect Disord. 2020 May 15;269:28-35.
- Young LM, Pipingas A, White DJ, Gauci S, Scholey A. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and ‘At-Risk’ Individuals. Nutrients. 2019 Sep 16;11(9):2232. doi: 10.3390/nu11092232.
- Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022 Mar 10;80(4):931-949.
- Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry. 2009;70 Suppl 5:12-7.
- Sangle P, Sandhu O, Aftab Z, Anthony AT, Khan S. Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression. Cureus. 2020 Oct 26;12(10):e11169. doi: 10.7759/cureus.11169.
- Leahy LG. Vitamin B Supplementation: What’s the Right Choice for Your Patients? J Psychosoc Nurs Ment Health Serv. 2017 Jul 1;55(7):7-11.
- Young SN, Ghadirian AM. Folic acid and psychopathology. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(6):841-63.
- Kocot J, Luchowska-Kocot D, Kiełczykowska M, Musik I, Kurzepa J. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders? Nutrients. 2017 Jun 27;9(7):659. doi: 10.3390/nu9070659.
- Han QQ, Shen TT, Wang F, Wu PF, Chen JG. Preventive and Therapeutic Potential of Vitamin C in Mental Disorders. Curr Med Sci. 2018 Feb;38(1):1-10.
- May JM. Vitamin C transport and its role in the central nervous system. Subcell Biochem. 2012;56:85-103.
- Shayganfard M. Are Essential Trace Elements Effective in Modulation of Mental Disorders? Update and Perspectives. Biol Trace Elem Res. 2022 Mar;200(3):1032-1059.
- Saghazadeh A, Mahmoudi M, Shahrokhi S, et al. Trace elements in schizophrenia: a systematic review and meta-analysis of 39 studies (N = 5151 participants). Nutr Rev. 2020 Apr 1;78(4):278-303.
- Firth J, Teasdale SB, Allott K, et al. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. 2019 Oct;18(3):308-324.
- Joe P, Petrilli M, Malaspina D, Weissman J. Zinc in schizophrenia: A meta-analysis. Gen Hosp Psychiatry. 2018 Jul-Aug;53:19-24.
- Sun R, Wang J, Feng J, Cao B. Zinc in Cognitive Impairment and Aging. Biomolecules. 2022 Jul 18;12(7):1000. doi: 10.3390/biom12071000.
- Joe P, Getz M, Redman S, et al. Serum zinc levels in acute psychiatric patients: A case series. Psychiatry Res. 2018 Mar;261:344-350.
- Grønli O, Kvamme JM, Friborg O, Wynn R. Zinc deficiency is common in several psychiatric disorders. PLoS One. 2013 Dec 19;8(12):e82793. doi: 10.1371/journal.pone.0082793.
- DiNicolantonio JJ, O’Keefe JH. The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders. Nutrients. 2020 Aug 4;12(8):2333. doi: 10.3390/nu12082333.
- Zhou L, Xiong JY, Chai YQ, et al. Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system. Front Psychiatry. 2022 Aug 31;13:933704. doi: 10.3389/fpsyt.2022.933704.
- Gao L, Wang J, Sekhar KR, et al. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J Biol Chem. 2007 Jan 26;282(4):2529-37.
- Sakai C, Ishida M, Ohba H, et al. Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells. PLoS One. 2017 Nov 9;12(11):e0187934. doi: 10.1371/journal.pone.0187934.
- Lewis JE, Poles J, Shaw DP, et al. The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review. J Clin Transl Res. 2021 Aug 4;7(4):575-620.
- Mocking RJ, Harmsen I, Assies J, et al. Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry. 2016 Mar 15;6(3):e756. doi: 10.1038/tp.2016.29.
- Grosso G, Galvano F, Marventano S, et al. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev. 2014;2014:313570. doi: 10.1155/2014/313570.
- Agostoni C, Nobile M, Ciappolino V, et al. The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD. Int J Mol Sci. 2017 Dec 4;18(12):2608. doi: 10.3390/ijms18122608.
- Karaszewska DM, Ingenhoven T, Mocking RJT. Marine Omega-3 Fatty Acid Supplementation for Borderline Personality Disorder: A Meta-Analysis. J Clin Psychiatry. 2021 May 4;82(3):20r13613. doi: 10.4088/JCP.20r13613.
- Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010 Dec;2(12):1231-46. doi: 10.3390/nu2121231.
- Vauzour D, Rodriguez-Mateos A, Corona G, et al. Polyphenols and human health: prevention of disease and mechanisms of action. Nutrients. 2010 Nov;2(11):1106-31.
- Vauzour D. Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxid Med Cell Longev. 2012;2012:914273. doi: 10.1155/2012/914273.
- Vauzour D. Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer’s disease pathophysiology. J Sci Food Agric. 2014 Apr;94(6):1042-56.
- Vauzour D. 2017. Polyphenols and brain health. OCL 24(2): A202. https://doi.org/10.1051/ocl/2017008
- Kennedy DO. Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits. Adv Nutr. 2014 Sep;5(5):515-33.
- Gomez-Pinilla F, Nguyen TT. Natural mood foods: the actions of polyphenols against psychiatric and cognitive disorders. Nutr Neurosci. 2012 May;15(3):127-33.
- Trebatická J, Ďuračková Z. Psychiatric Disorders and Polyphenols: Can They Be Helpful in Therapy? Oxid Med Cell Longev. 2015;2015:248529. doi: 10.1155/2015/248529. Epub 2015 Jun 9.
- Lin K, Li Y, Toit ED, Wendt L, Sun J. Effects of Polyphenol Supplementations on Improving Depression, Anxiety, and Quality of Life in Patients with Depression. Front Psychiatry. 2021 Nov 8;12:765485. doi: 10.3389/fpsyt.2021.765485.
- Leri M, Scuto M, Ontario ML, et al. Healthy Effects of Plant Polyphenols: Molecular Mechanisms. Int J Mol Sci. 2020 Feb 13;21(4):1250. doi: 10.3390/ijms21041250.
- Kontogianni MD, Vijayakumar A, Rooney C, et al. A High Polyphenol Diet Improves Psychological Well-Being: The Polyphenol Intervention Trial (PPhIT). Nutrients. 2020 Aug 14;12(8):2445. doi: 10.3390/nu12082445.
- Vojdani A, O’Bryan T, Green JA, Mccandless J, Woeller KN, Vojdani E, Nourian AA, Cooper EL. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 Jun;7(3):151-61.
- Ruggieri M. et al. Low prevalence of neurologic and psychiatric manifestations in children with gluten sensitivity. Journal of Pediatrics. 2008 Feb;152(2):244-9. Epub 2007 Nov 19.
- Ruggieri M, et al. Low prevalence of neurologic and psychiatric manifestations in children with gluten sensitivity. Journal of Pediatrics. 2008;152(2):244-9.
- Dickerson F, et al. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disorders. 2011 Feb;13(1):52-8. doi: 10.1111/j.1399-5618.2011.00894.x.
- Dickerson F. et al. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disorders. 2011 Feb;13(1):52-8. doi: 10.1111/j.1399-5618.2011.00894.x.
- Dickerson F, et al. Markers of gluten sensitivity in acute mania: A longitudinal study. Psychiatry Research. 2012. doi:10.1016/j.psychres.2011.11.007
- Dickerson F. et al. Markers of gluten sensitivity in acute mania: A longitudinal study. Psychiatry Research. 2012 Mar 2. [Epub ahead of print].
- Whiteley P, Shattock P, Knivsberg AM, et al. Gluten- and casein-free dietary intervention for autism spectrum conditions. Front Hum Neurosci. 2013 Jan 4;6:344. doi: 10.3389/fnhum.2012.00344.
- Peters SL, Biesiekierski JR, Yelland GW, et al. Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity – an exploratory clinical study. Aliment Pharmacol Ther. 2014;39(10):1104-12. doi:10.1111/apt.12730
- Busby E, Bold J, Fellows L, Rostami K. Mood Disorders and Gluten: It’s Not All in Your Mind! A Systematic Review with Meta-Analysis. Nutrients. 2018;10(11). doi:10.3390/nu10111708
- Sumathi T, Manivasagam T, Thenmozhi AJ. The Role of Gluten in Autism. Adv Neurobiol. 2020;24:469-479.
- Croall ID, Hoggard N, Hadjivassiliou M. Gluten and Autism Spectrum Disorder. Nutrients. 2021 Feb 9;13(2):572. doi: 10.3390/nu13020572.
- Perlmutter D, Loberg K. Grain Brain. 2013. Little, Brown and Company. 237 Park Ave. New York, NY 10017.
- Philpott WH, Kalita DK. Brain Aleergies. 2000. Keats Publishing. 4255 West Touhy Ave, Lincolnwood (Chicago), Illinois 60712.
- Braly J, Hoggan R. Dangerous Grains. 2002. Avery, a member of Penguin Group Inc. 375 Hudson Street, New York, NY 10014.
- Poloni N, Vender S, Bolla E, et al. Gluten encephalopathy with psychiatric onset: case report. Clin Pract Epidemiol Ment Health. 2009 Jun 26;5:16. doi: 10.1186/1745-0179-5-16.
- Aucoin M, Bhardwaj S. Major Depressive Disorder and Food Hypersensitivity: A Case Report. Neuropsychobiology. 2019;78(4):249-255.
- Saji Parel N, Krishna PV, Gupta A, et al. Depression and Vitamin D: A Peculiar Relationship. Cureus. 2022 Apr 21;14(4):e24363. doi: 10.7759/cureus.24363.
- https://www.pbs.org/wgbh/frontline/article/jenny-mccarthy-were-not-an-anti-vaccine-movement-were-pro-safe-vaccine/
- Lionetti E, Leonardi S, Franzonello C, et al. Gluten Psychosis: Confirmation of a New Clinical Entity. Nutrients. 2015 Jul 8;7(7):5532-9.
- Genuis SJ, Lobo RA. Gluten sensitivity presenting as a neuropsychiatric disorder. Gastroenterol Res Pract. 2014;2014:293206. doi: 10.1155/2014/293206.
- Herken J, Prüss H. Red Flags: Clinical Signs for Identifying Autoimmune Encephalitis in Psychiatric Patients. Front Psychiatry. 2017 Feb 16;8:25. doi: 10.3389/fpsyt.2017.00025.
- Xu L, Chen Z. Anti-NMDA Receptor Encephalitis Misdiagnosed As Generalized Anxiety Disorder: A Case Report. Cureus. 2021 Dec 20;13(12):e20529. doi: 10.7759/cureus.20529.
- Norwitz NG, Saif N, Ariza IE, Isaacson RS. Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers. Nutrients. 2021 Apr 19;13(4):1362. doi: 10.3390/nu13041362.
- Jakobsen JC, Gluud C, Kirsch I. Should antidepressants be used for major depressive disorder? BMJ Evid Based Med. 2020 Aug;25(4):130. doi: 10.1136/bmjebm-2019-111238. Epub 2019 Sep 25. PMID: 31554608; PMCID: PMC7418603.
- Kirsch I. The emperor’s New Drugs – Exploding the Antidepressant Myth. Basic Books. 2010. New York, NY 10016.
- Healy D, Herxheimer A, Menkes DB. Antidepressants and violence: problems at the interface of medicine and law. PLoS Med. 2006 Sep;3(9):e372. doi: 10.1371/journal.pmed.0030372.
- Molero Y, Lichtenstein P, Zetterqvist J, Gumpert CH, Fazel S. Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study. PLoS Med. 2015 Sep 15;12(9):e1001875. doi: 10.1371/journal.pmed.1001875.
- Bielefeldt AØ, Danborg PB, Gøtzsche PC. Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers. J R Soc Med. 2016 Oct;109(10):381-392.
- Hemminki E, Merikukka M, Gissler M, et al. Antidepressant use and violent crimes among young people: a longitudinal examination of the Finnish 1987 birth cohort. J Epidemiol Community Health. 2017 Jan;71(1):12-18. doi: 10.1136/jech-2016-207265. Epub 2016 Jun 28. PMID: 27354489.
- Lagerberg T, Fazel S, Molero Y, et al. Associations between selective serotonin reuptake inhibitors and violent crime in adolescents, young, and older adults – a Swedish register-based study. Eur Neuropsychopharmacol. 2020 Jul;36:1-9. doi: 10.1016/j.euroneuro.2020.03.024. Epub 2020 May 29. PMID: 32475742; PMCID: PMC7347007.
- Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD000448. doi: 10.1002/14651858.CD000448.pub3.
- Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016 Sep 2;5(1):148. doi: 10.1186/s13643-016-0325-2.
- Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. J Affect Disord. 2017 Mar 1;210:211-221.
- Lowe H, Toyang N, Steele B, et al. The Therapeutic Potential of Psilocybin. Molecules. 2021 May 15;26(10):2948. doi: 10.3390/molecules26102948.
- Sarris J, Sinclair J, Karamacoska D, et al. Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review. BMC Psychiatry. 2020 Jan 16;20(1):24. doi: 10.1186/s12888-019-2409-8.