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Hot Publication – Tripp et al.

Brain-derived Neurotrophic Factor Signaling and Subgenual Anterior Cingulate Cortex Dysfunction in Major Depressive Disorder
Tripp A, Oh H, Guilloux JP,Martinowich K, Lewis DA, Sibille E.

Understanding the primary pathology in major depression remains elusive, and it is estimated that current treatments of the illness result in just 33% of patients achieving a complete recovery. A recent study conducted by Adam Tripp, MD, PhD, Hyunjung Oh, MS, their mentor Etienne Sibille, PhD, and colleagues suggests that alternative molecular targets may be susceptible in the disease process of depression, opening-up new approaches for future research for the treatment of depression.  For this study, investigators in the Department of Psychiatry evaluated gene expression in two molecular pathways (GABA and brain derived neurotrophic factor-BDNF) thought to be involved in the pathophysiology of major depression in two key brain regions that regulate emotion (anterior cingulate cortex and amygdala). To study these pathways, Tripp et al. examined changes in both postmortem human brains and in mouse genetic models. The observed alterations in GABA and BDNF pathways in humans were recreated by the mouse models, suggesting that specific cellular (e.g. somatostatin interneurons) and functional (e.g. dendritic inhibition) elements of brain circuitry may be acutely vulnerable and adversely affected in depression.

Contributors:

Adam Tripp, MD, PhD, Hyunjung Oh, MS, David Lewis, MD, and Etienne Sibille, PhD (Department of Psychiatry and the Center for Neuroscience, University of Pittsburgh)

Jean-Philippe Guilloux, PhD (Université Paris-Sud, Châtenay-Malabry, France)

Keri Martinowich, PhD (Lieber Institute for Brain Development, Johns Hopkins University School of Medicine)

The results of this investigation were published in the November 2012 issue of the American Journal of Psychiatry. Click here for a link to the abstract.