Abstract
Mood disorders are characterized by increased proinflammatory activity, anhedonia, abnormal neurophysiological responses to emotionally-valenced faces, and neuromorphometric abnormalities of the hippocampus and (particularly the left) subgenual anterior cingulate cortex (sgACC). However, the relationship between these variables is unclear. We performed whole-genome transcriptomics analysis on peripheral blood mononuclear cells obtained from 24 healthy subjects and 29 unmedicated, currently depressed patients with a primary mood disorder (bipolar disorder and major depressive disorder). Thirteen out of 26 genes that showed both >1.25-fold expression changes and statistically significant differences between groups were previously implicated in neurological and/or inflammatory disease (CFD, NUCKS1, CTSZ, CD160, IL23A, SERTAD1, NFKBIZ, IER5, CITED2, APBB3, ADM, TNF, and NR4A2). Moreover, the comparison of the mood disordered versus healthy samples implicated a single Ingenuity Pathway Analysis gene network. Consistent with the hypothesis that increased expression of proinflammatory cytokines can diminish the pleasure experienced in response to positive stimuli, analogous to ‘sickness behavior’, anhedonia ratings correlated positively with gene expression of APBB3, CITED2, IER5, NR4A2, and TNF. Expression of CITED2 and APBB3 as well as the dopamine-related NR4A2 gene correlated inversely with the BOLD response to masked happy faces in the rostral ACC/ventromedial PFC and posterior cingulate. In the mood disorder group, a significant positive correlation was found between gray matter thickness of the left sgACC, measured using FreeSurfer, and expression of CITED2 and NR4A2.
Published Version
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