Research

Dr. Robert McMullen discusses the impact of a variety of well-known supplements and nutraceuticals and their impact on patients with depression.

How does a small molecule blocking a few receptors change a patients’ passionately held paranoid belief that the FBI is out to get him? To address this central puzzle of anti-psychotic action, we review a framework linking dopamine neurochemistry to psychosis, and then link this framework to the mechanism of action of antipsychotics. Normal dopamine transmission has a role in predicting novel rewards and in marking and responding to motivationally salient stimuli. Abnormal dopamine transmission alters these processes and results in an aberrant sense of novelty and inappropriate assignment of salience leading to the experience of psychosis.

Antipsychotics improve psychosis by diminishing this abnormal transmission by blocking the dopamine D2/3 receptor (not D1 or D4), and although several brain regions may be involved, it is suggested that the ventral striatal regions (analog of the nucleus accumbens in animals) may have a particularly critical role. Contrary to popular belief, the antipsychotic effect is not delayed in its onset, but starts within the first few days. There is more improvement in the first 2 weeks, than in any subsequent 2-week period thereafter. However, a simple organic molecule cannot target the complex phenomenology of the individual psychotic experience. Antipsychotics diminish dopamine transmission and thereby dampen the salience of the preoccupying symptoms. Therefore, in the initial stage of an antipsychotic response, the patients experience a detachment
from symptoms, a relegation of the delusions and hallucinations to the back of their minds, rather than a complete erasure of the symptoms. Only with time, and only in some, via the mediation of new learning and plasticity, is there a complete resolution of symptoms. The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed.

Select research suggests that wireless radiation from cell phones, wireless internet, and other signals can affect a baby in the womb or even directly following its birth. The Babysafe Project provides such research and we’ve provided the link here for information on this topic and how to protect your child prior to birth.

Professor Heather Ashton outlines how various benzodiazepine medications work and how withdrawal works in the human body.

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. We 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.

Total and LDL cholesterol measured in 9, 15 and 18 years old boys predicted Disinhibition and Thoughtlessness in 25 years old young adults. High scores of Disinhibition were associated with low total and LDL cholesterol levels in males but, while less consistently, with high total and LDL cholesterol levels in females. Cross-sectional analysis did not result in systematic outcomes.