Chemical Biology

Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In this 2006 study, researchers completed a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene with the possibility of others that may be unknown in the environment.

The microbiome consists of microbes that are both helpful and potentially harmful. Most are symbiotic (where both the human body and microbiota benefit) and some, in smaller numbers, are pathogenic (promoting disease). In a healthy body, pathogenic and symbiotic microbiota coexist without problems. But if there is a disturbance in that balance—brought on by infectious illnesses, certain diets, or the prolonged use of antibiotics or other bacteria-destroying medications—dysbiosis occurs, stopping these normal interactions. As a result, the body may become more susceptible to disease. This article provides information about the microbiome and its affect on mental health.

Growing evidence supports the hypothesis that epigenetics is a key mechanism through which environmental exposures interact with an individual’s genetic constitution to determine risk for depression throughout life. Epigenetics, in its broadest meaning, refers to stable changes in gene expression that are mediated via altered chromatin structure without modification of DNA sequence. According to this hypothesis, severe stress triggers changes—in vulnerable individuals—in chromatin structure at particular genomic loci in the brain’s limbic regions, which drive sustained changes in gene expression that contribute to episodes of depression.

In a pilot study aimed at investigating the effectiveness of targeted nutrient therapy, the clinical progress of 567 patients with a range
of mental illnesses receiving established medical treatment in conjunction with a targeted nutrient program were assessed by clinical outcome after 12 months.

In this article, the interviewer speaks with Dr. Kelly Brogan, a leading voice in natural approaches to women’s mental health. With degrees from MIT and Weil Cornell Medical College, triple board certification in psychiatry, psychosomatic medicine and integrative holistic medicine, and direct experience practicing within the parameters of conventional psychiatry, Dr. Brogan is uniquely qualified to challenge the pseudoscience of the chemical imbalance theory and the drug regimens that it spawned. This conversation addressed Dr. Brogan’s grave concerns about the recent rollout of Zulresso (brexanolone), a drug specifically designed, and approved by the FDA for the treatment of Postpartum Depression.

Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. Joshua L. Roffman, MD, and others examined physiologic and clinical effects of L-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received L-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (PANSS, SANS, CDSS), cognition (MATRICS composite) and three complementary MRI measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared to placebo, L-methylfolate increased plasma methylfolate levels (d=1.00, p=.0009) and improved PANSS Total (d=.61, p=.03) as well as PANSS Negative and General Psychopathology subscales. While PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving L-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity, and increased cortical thickness. In conclusion, L-methylfolate supplementation was associated with salutary physiologic changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials.