This website describes research that may offer new insights into the causes of mental illness, or that may suggest complementary or alternative treatments.
Nothing in this website is intended to replace personalized medical advice. Do not enact any medication changes based on what you find here without first discussing it with a qualified medical provider.
A recent clinical study of melatonin to prevent migraine headache unexpectedly found a possible weight loss effect of melatonin. The study was conducted by Andre Leite Gonçalves and colleagues from Albert Einstein Hospital, São Paulo, Brazil.
The study was well-designed and compared the effects of a standard migraine treatment medication (amitriptyline, 25 mg at bedtime) to a nightly 3 mg dose of melatonin among groups of men and women with frequent migraine headaches (2 to 8 migraine attacks per month). The study also included a parallel placebo group, and was conducted in double-blind fashion. Neither the patients nor the study doctors knew who was getting an active drug or a placebo. The study lasted 12 weeks, and approximately 60 subjects were in each treatment group.
Melatonin appeared highly effective at reducing 
migraine frequency. By study’s end, over half of the patients taking melatonin reported a greater than 50% reduction of headache frequency. In contrast, only 20% of those in the placebo group experienced a reduction of that magnitude. Melatonin treatment also beat amitriptyline treatment; just under 40% of amitriptyline-treated patients were designated as responders.
In addition to the obvious possibility that migraines were less frequent because patients might have been sleeping better, the authors offer several possible explanations for the ability of melatonin to prevent migraines. Melatonin possesses anti-inflammatory properties, can regulate blood flow within the brain, and can affect the actions of several important neurotransmitter substances.
An unexpected finding was that patients in the nightly 
melatonin group, on average, lost a bit of weight while those in the placebo group gained almost a pound and those in the amitriptyline group gained about 2 pounds over the course of 12 weeks. (Amitriptyline is one of many psychoactive medications with a side effect of weight gain). The magnitude of weight loss in the melatonin group was really very small (a third of a pound, on average). But the fact those in the other groups gained is remarkable. This finding is in line with a body of basic science research that points to an ability of melatonin to regulate metabolism and weight.
Many animal studies support a role for melatonin in weight loss. Melatonin can inhibit the maturation of isolated fat cells. Melatonin reduced weight gain and fat accumulation in rats subjected to obesity-generating high calorie diets. Like humans, rats at middle age begin to grow fat, and daily melatonin reverses middle age obesity, even at low doses that did not measurably increase blood levels. Melatonin can increase the amount of “brown fat” in many animal species, and it is speculated that this may apply as well to humans. Brown fat is metabolically very active, and can burn calories just to generate body heat. So, having more brown fat would be a great advantage in the fight against weight gain. Taken together, these studies suggest that melatonin can regulate food intake, energy metabolism, fat storage and body weight.
This study is among the first to suggest an ability to melatonin to prevent weight gain. Many psychotropic medications cause unwanted weight gain. Emerging research suggests that melatonin may slow down weight gain when olanzapine is used in the treatment of first episode psychosis, and may reverse weight gain when second generation antipsychotic medications are used to treat bipolar disorder.
Melatonin is available over the counter in the USA and many other countries. It has a low side effect/risk profile that is appealing to many potential users. It would be worthwhile to see if there are specific demographic groups or illness types that preferentially respond to melatonin. Or whether the weight gain blocking effect is more robust with particular types of medications.
Slides from a lecture addressing the causes of psychotic illness, how often it occurs, and some first-line treatment options
An over-the-counter dietary supplement can help people quit smoking, according to a newly-released study. The supplement, N-acetylcysteine, also reduced depression.
N-acetylcysteine is derived from cysteine, an essential amino acid obtained from dietary protein. N-acetylcysteine has a long history of use in medicine. It is used to prevent liver damage from acetaminophen (paracetamol) overdose. It is also sometimes used to improve breathing in some types of lung disease.
In recent years, scientists have discovered that N-acetylcysteine is also psychotropic. There are at least two ways in which it can affect brain function. First, N-acetylcysteine is an antioxidant. Many psychiatric conditions are associated with excessive production of oxygen-derived free radicals, or with decreased antioxidant defenses. When free radicals and antioxidant defense levels are imbalanced, this is called oxidative stress. N-acetylcysteine can increase levels of glutathione, which is a major player in the body’s oxidative defense system. So, N-acetylcysteine may help to reduce oxidative stress in the brain. A second major action of N-acetylcysteine is its ability to interact with the glutamate neurotransmitter system. Glutamate is the most abundant neurotransmitter in the brain. Imbalanced glutamate signaling is implicated as a possible contribution toward addictive disorders – as well as toward depression.
Eduardo Prado, Michael Mays and colleagues conducted a study in which smokers who had already failed to respond to medication assistance (nicotine replacement therapy; or varenicline/Chantix; or bupropion/Wellbutrin/Zyban) were invited to participate. In the study, all volunteers participated in smoking-focused psychotherapy and half received either placebo capsules or N-acetylcysteine for a total of 12 weeks. N-acetylcysteine was dosed at 3000 mg per day (delivered as 1500 mg, twice-daily doses).
The quit rate for the N-acetylcysteine group was 47%, while only 21% of placebo-treated volunteers were able to quit by the end of 12 weeks.
At the beginning of the study, the average daily use was 20 cigarettes per day. By twelve weeks, the N-acetylcysteine group smoked, on average, 9 cigarettes per day. Placebo group volunteers smoked an average of 16 cigarettes per day.
Depression scores went down in both groups, but the N-acetylcysteine group had significantly greater reduction of depression. Hamilton Depression Rating Scale scores declined more than 40% in the N-acetylcysteine group.
Side effect reports were mild. Nausea was the most commonly reported side effect. Diarrhea, skin allergy, and respiratory allergy also occurred.
The major caveat of this study is its small sample size. Of the 31 volunteers who were enrolled, 18 completed the entire study. (6 volunteers dropped out in the active treatment group; 7 dropped out from the placebo group). So it remains to be seen if these findings can be generalized to a broad population. On the other hand, these findings are remarkable because they were obtained from a difficult-to-treat sample of long-term pack-a-day smokers for whom prior medication therapy had failed.
Here is a copy of the powerpoint slides used for a lecture at the Mason Community Center on 11 February 2015. The general theme is the relationship between diet/nutrition and mental health/illness.
Topics addressed include: 1) the heterogeneity of psychiatric diagnoses; 2) the various types of fatty acids, and 3) their relationship to mental health; 4) relationship between the composition of the diet and measures of depression, anxiety, and well-being; 5) the relationship between obesity and depression; and 6) brief comments on the relationship between gluten and schizophrenia.
The bottom line regarding foods: mental well-being seems best served by whole food diets rich in vegetables, fruits, whole grains, legumes, fish, and poultry. Processed food, junk food, and convenience foods seem to increase the risk for depression and anxiety.
Here is the powerpoint slide deck: Diet and Mental Health Lecture Notes
Dr. Leonard John Hoffer, Professor of Medicine at McGill University reviewed the potential roles of vitamin deficiencies as a possible cause of schizophrenia, and whether or not they may be of some value in its treatment.
He focuses on the possible roles of folic acid, vitamin C, and niacin.
The entire review article is free to download.
Here are a few notable quotes from the article:
“Organic brain disorders indistinguishable from schizophrenia may be induced by certain drugs and by neurological, metabolic, inflammatory and infectious diseases. Such disorders account for approximately 5% of cases initially diagnosed as first-episode schizophrenia by expert psychiatrists.”
“Clinical reports have described abnormal folic acid and vitamin B12 metabolism in some people with schizophrenia. A genetic defect in folic acid metabolism has been shown to cause a schizophrenic syndrome. The addition of 15mg/day of methylfolate to standard psychiatric therapy improved the clinical and social recovery of patients with acute schizophrenia.”
“Ascorbic acid deficiency is well known in chronic schizophrenia (37) and regrettably is not a relic of the past, having been observed in approximately one-third of the patients in a modern British mental hospital… Two double-blind randomized clinical trials (37, 44), an open trial (45) and a case report (46) indicate that the symptoms of chronic schizophrenia can be ameliorated by high-dose ascorbic acid therapy.”
A new study shows that playing Tetris can reduce naturally-occurring cravings.
Jessica Skorka-Brown led a study at Plymouth University in which college students were asked to rate their cravings on a scale of 0 (no cravings at all) to 100 (craving something very much). Most of the participants (58, to be exact) craved food or drink. Others reported cravings for caffeine (10) or nicotine (12).
After scoring their initial craving strength, the study subjects were randomly assigned to a computer that let them play Tetris for three minutes, or to a computer that merely showed a “game loading” image sequence for the same amount of time.
Craving strength did not change much in the group that got the dummy computers. Their average craving strength declined by 5% (from an initial score of 58 to a final score of 55). In contrast, playing Tetris for three minutes caused a 24% drop in craving strength (from 59 to 45).
Craving something involves memories – lots of memories. Many of these memories involve images and remembered sensations of the desired thing. These memories can become so numerous and so strong that they may overload the brain’s short term working memory buffers, making it difficult for someone to use those memory buffers to come up with reasons not to indulge in the craving.
This study adds to a growing body of literature showing that it is possible to reduce cravings by engaging the ‘visuospatial sketchpad’ of working memory. Cravings for cigarettes as well as for chocolate are reduced when research subjects occupy their working memories with other images.
Cravings appear to take control of our short-term memory, robbing us of mental resources needed to resist the urge. Deliberately occupying our attention and memory, with games that engage visual problem solving, may clear the slate and give us the freedom to choose the next object of our full attention.
Acetyl-l-carnitine is the subject of over 1000 scientific papers in the Medline database. It is a natural product with very interesting reported benefits when used as a supplement. Maurizio Rossini and colleagues from the University of Verona report that the benefits of acetyl-l-carnitine include reducing pain and depression in patients with fibromyalgia.
They recruited 102 volunteers from 7 different Italian rheumatology clinics. To be eligible for the study, volunteers had to have a diagnosis of fibromyalgia syndrome, according to the criteria established by the American College of Rheumatology. Volunteers also had to have at least 11 positive trigger points to be included in the study.
Volunteers were randomly assigned to a placebo treatment group, or an active treatment group. The active treatment was acetly-l-carnitine at a dose of 1500 mg daily for ten weeks.
The placebo response in this study was pretty strong. For the first six weeks, pain scores dropped equally well in both the placebo group and the acetyl-l-carnitine group. However, beyond 6 weeks there was no further improvement in the placebo group. On the other hand, patients taking acetyl-l-carnitine continued to improve. At the end of 10 weeks, the acetly-l-carnitine-treated patients clearly surpassed the placebo group. Acetyl-l-carnitine significantly reduced the number of trigger points, and also decreased the objectively-measured pain threshold.
The study also showed that showed that acetyl-l-carnitine reduced depression.
Acetyl-l-carnitine is a very interesting molecule. It serves as an “acetyl group donor” within the body. (An acetyl group is the organic chemistry term for a particular arrangement of 2 carbon atoms attached to an oxygen atom). Acetyl groups are an extremely important source of cellular energy. Structures called mitochondria inside each cell can convert acetyl groups into ATP, which is the ultimate energy currency of living systems. Through a process called histone acetylation, the body also uses acetyl groups to control the expression of various genes.
Possibly by influencing gene expression, acetyl-l-carnitine increases levels of nerve growth factors within the brain. Acetyl groups from acetyl-l-carnitine can find their way into the neurotransmitter acetylcholine, a neurotransmitter involved in memory. Acetyl-l-carnitine also appears to increase levels of serotonin and dopamine in the brain.
In their discussion of their findings, Dr. Rossini and his co-authors cite prior work showing that acetyl-l-carnitine improves fatigue in patients with chronic fatigue syndrome and in multiple sclerosis, and also reduces pain associated with diabetic neuroropathy.
In comparing the magnitude of beneficial effects seen in this study with those reported from other treatments, acetyl-l-carnitine seems about equal to duloxetine (Cymbalta) and pregabalin (Lyrica).
Acetyl-l-carnitine has no major pharmaceutical sponsorship. Its potential benefits are not advertised or promoted to clinicians. However, considering its effect size in this study and its low risk for side effects, it seems worthwhile to consider its use as part of the treatment for fibromyalgia.
Bad nutrition and bad behavior are related, according to a British study on the effect of dietary supplements on antisocial behavior.
The study, led by Dr Bernard Gesch, randomly assigned 231 prison inmates to nutritional supplements or to identical placebos. The supplements consisted of a commercially available multivitamin (Forceval) plus an essential fatty acid supplement (Efamol). The average duration of treatment was 142 days.
The researchers kept track of how many times the study participants were found, after a judicial hearing, to have broken prison rules. The results were astonishing.
There was a 7% reduction in the rate of offending in the placebo group, compared to a 35% reduction in the group that took the vitamin/fatty acid supplements.
There were similarly strong results in the rate of violent offenses: a 10% reduction in the placebo group versus a 37% reduction in the supplements group.
This study has several important strengths that make it especially convincing.
In the words of the study’s authors:
Dialectical Behavior Therapy normalizes the overactive amygdala of borderline personality disorder.
New research shows that a specialized from of psychotherapy can reduce mood swings and calm a hyperactive brain region in patients with borderline personality disorder. These beneficial changes in emotional reactivity and brain function happened without the use of any medications. The findings highlight the value of a specialized psychotherapy and demonstrate that psychotherapy alone can help to restore neurological balance in one of the brain’s key emotion control centers.
Deep within each of the brain’s temporal lobes is a relatively small structure called the amygdala. It was named after the Greek word for almond because of its size and shape. This brain almond is a key player in the initial experience of emotions – and can even rekindle feelings throughout the body when we recall past emotional events. Scientists can observe amygdala activity by using functional MRI. When research subjects are shown emotionally expressive faces, the amygdala lights up with activity.
If amygdala activity is part of emotional experience, then amygdala hyperactivity can lead to overwhelming emotions, perhaps to the point of contributing to mental illness. Borderline personality disorder is a condition in which people experience extreme and highly reactive, sometimes incapacitating moods. When borderline personality patients are shown emotionally-evocative images, their amygdala response is decidedly hyperactive. Under normal circumstances, amygdala activity fades if the same image is shown over and over again. Not so in the case of borderline personality. This “lack of habituation” of amygdala activity may account for the difficulty many borderline patients report in “letting go” of a painful memory.
Dialectical Behavior Therapy was developed to help people gain control of their thoughts and behaviors by teaching skill and techniques when people find that life situations or even stressful memories start to create emotional havoc. It is the most widely studied form of treatment for borderline personality disorder. Over 17 well-conducted clinical studies demonstrate its benefits. Up to this point, most of the recognized benefits have been in areas of life quality, or reported control of moods and mood swings. Very little is known about whether this form of psychotherapy can actually change brain function. A new report by Marianne Goodman from the Bronx VA Medical Center shows that dialectical behavior therapy not only improves emotional regulation, but also can actually calm the overactive amygdala of borderline personality.
Dr. Goodman and her colleagues measured amygdala reactions in 11 patients who viewed emotion-evoking pictures while undergoing functional MRI scans of their brains. The amygdala response in the borderline patients was significantly higher than in a healthy comparison group. The patients then participated in Dialectical Behavior Therapy, which consisted of weekly skills-training classes and weekly individual meetings with a DBT therapist who reviewed and coached the implementation of emotion-regulating skills in patients’ daily lives.
After 12 months of therapy, the patients repeated their exposures to emotion-charged images while their brains were again scanned to measure amygdala activity. The researchers observed more normal amygdala activity at the end of the therapy. Patients also experienced less problematic emotional reactivity in their daily lives. Scores on the emotional regulation questionnaires correlated strongly with the measured reductions of amygdala activation.
Borderline personality disorder can be seen as “emotional ADHD.” Patients experience hyper-reactive and extreme emotions. An overactive amygdala may be to blame. This study shows that Dialectical Behavior Therapy can help to restore emotional balance and may do so by training the amygdala. That it can do this without relying on medications is even more impressive.
Paul Amminger and colleagues published results of a small study with big results. They suggest that omega-3 fatty acids improve the overall level of functioning and reduce the severity of numerous psychiatric symptoms in young people with borderline personality disorder.
The data are from a larger study led by Dr. Amminger at the University of Viennna, Austria. The parent study involved young people with symptoms that suggested a high risk of progressing psychosis. The parent study, enrolled 81 adolescents (average age of 14 to 18 years) thought to be at “ultra-high risk of psychosis.” From that sample, they found and followed 15 patients who also had borderline personality disorder.
About half of the group took an omega-3 supplements that delivered 700 mg of EPA plus 480 mg of DHA per day. The other half took identical placebos containing fish-flavored coconut oil. The study lasted 12 weeks.
By the end of the study, 29% of the patients in the placebo group proceeded to show signs of psychosis; while this happened to none of the omega-3 users.
The overall level of functioning improved substantially among the borderline personality patients in the omega-3 treated group. In contrast, functioning remained stable yet impaired in the placebo group. (The investigators used the Global Assessment of Functioning Scale to gauge functional status).
Psychiatric symptoms were measured in the study using a rating scale called the Positive and Negative Symptoms Scale (PANSS). Using this measurement scale, the researchers discovered that omega-3 treatment had the biggest impact on: Depression, Feelings of suspiciousness or persecution; Tension; Emotional withdrawal; Anxiety; and Impaired impulse control. They used PANSS symptom subscales to construct a Borderline Personality Severity Score (comprised of items related to suspiciousness, tension, and poor impulse control), and found a very large therapeutic response to the omega-3 treatment.
Although their study group consisted of a relatively small number of volunteers, the effects of the omega-3 treatment were very large. The data suggest that omega-3 fatty acids, at the right doses for a long-enough period of time, can significantly improve the quality of life for people with borderline personality disorder.
