Differential Treatment Response, Neuroinflammation, and Psychosis Associated with Chromosome Deletion

Abstract

Dr. Hollander is the editor of this journal, Esther and Joseph Klingenstein Professor and Chairman of Psychiatry at the Mount Sinai School of Medicine, and director of the Seaver and New York Autism Center of Excellence in New York City. There is substantial evidence that obsessivecompulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to treatment interventions. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram/placebo, was investigated by Dan J. Stein, MD, PhD, and colleagues. Factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/ checking, hoarding/symmetry, religious/sexual, and somatic/hypochondriacal). While escitalopram exhibited good efficacy across the range of OCD symptom dimensions, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to fully delineate the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity. A greater understanding of subfactors within various symptom domains may eventually lead to greater understanding of differential treatment outcomes. Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. Jonas Hannestad, MD, PhD, and colleagues reviewed how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-α treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation, which could interfere with excitatory amino acid metabolism, leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of antiand pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation may ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression. Thus, psychiatric disorders, such as depression, may benefit from a greater understanding of the role of inflammation in its pathophysiology. Medical specialties, such as rheumatology, have benefited from greatly expanded treatment options for inflammation in recently. Varenicline has demonstrated efficacy in the promotion of smoking cessation. However, from the time of initial trials, it has been associated with significant psychiatric adverse effects. Andres J. Pumariega, MD, and colleagues describe a case where mixed mood and psychotic disturEditor’s Letter