Characterization of the molecular pathology of depression in human postmortem subjects.

Overview:

Our research goals have focused on translational research aimed at identifying the cellular and molecular basis of major depression, using genomic, proteomic, genetic/epigenetic and single cell studies in postmortem brains of depressed and control subjects. We have provided direct evidence for BDNF- and GABA-related pathologies in depression with gender- and brain region-specific features. These studies provide supporting evidence and potential links between two major hypotheses of depression, namely the reduced neurotrophic support and altered GABA hypothesis. Combined with imaging evidence from other groups, we have proposed a model linking molecular, cellular, biochemical, and neural network findings for a role of cortical GABA neurons in the increased self-focus/rumination symptom dimension in depression. This coherent translational model has now generated testable hypotheses for a dimensional and symptom-based investigation of altered GABA function in neuropsychiatric disorders.

 

Publications:

 – Scifo E, Pabba M, Kapadia F, Ma T, Lewis DA, Tseng GC, Sibille E. Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder. Biol Psychiatry. 2018 Jan 1;83(1):81-89. PubMed PMID: 28935211; PubMed Central PMCID: PMC5705452.

– Ding Y, Chang LC, Wang X, Guilloux JP, Parrish J, Oh H, French BJ, Lewis DA, Tseng GC, Sibille E. Molecular and Genetic Characterization of Depression: Overlap with other Psychiatric Disorders and Aging. Mol Neuropsychiatry. 2015 May;1(1):1-12. PubMed PMID: 26213687; PubMed Central PMCID: PMC4512183.

– Tripp A, Oh H, Guilloux JP, Martinowich K, Lewis DA, Sibille E. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry. 2012 Nov;169(11):1194-202. PubMed PMID: 23128924; PubMed Central PMCID: PMC3638149.

– Guilloux JP, Douillard-Guilloux G, Kota R, Wang X, Gardier AM, Martinowich K, Tseng GC, Lewis DA, Sibille E. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry. 2012 Nov;17(11):1130-42. PubMed PMID: 21912391; PubMed Central PMCID: PMC3237836.