Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder

9Citations
Citations of this article
54Readers
Mendeley users who have this article in their library.

Abstract

Background Major depressive disorder (MDD) is a debilitating mental illness and a major cause of lost productivity worldwide. MDD patients often suffer from lifelong recurring episodes of increasing severity, reduced therapeutic response, and shorter remission periods, suggesting the presence of a persistent and potentially progressive pathology. Methods Subgenual anterior cingulate cortex postmortem samples from four MDD cohorts (single episode, n = 20; single episode in remission, n = 15; recurrent episode, n = 20; and recurrent episode in remission, n = 15), and one control cohort (n = 20) were analyzed by mass spectrometry–based proteomics (n = 3630 proteins) combined with statistical analyses. The data was investigated for trait and state progressive neuropathologies in MDD using both unbiased approaches and tests of a priori hypotheses. Results The data provided weak evidence for proteomic differences as a function of state (depressed/remitted) or number of previous episodes. Instead it suggested the presence of persistent MDD effects, regardless of episodes or remitted state, namely on proteomic measures related to presynaptic neurotransmission, synaptic function, cytoskeletal rearrangements, energy metabolism, phospholipid biosynthesis/metabolism, and calcium ion homeostasis. Selected proteins (dihydropyrimidinase-related protein 1, synaptosomal-associated protein 29, glutamate decarboxylase 1, metabotropic glutamate receptor 1, and excitatory amino acid transporter 3) were validated by Western blot analysis. The findings were independent of technical, demographic (sex or age), or other clinical parameters (death by suicide and drug treatment). Conclusions Collectively, the results provide evidence for persistent MDD effects across current episodes or remission, in the absence of detectable progressive neuropathology.

Cite

CITATION STYLE

APA

Scifo, E., Pabba, M., Kapadia, F., Ma, T., Lewis, D. A., Tseng, G. C., & Sibille, E. (2018). Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder. Biological Psychiatry, 83(1), 81–89. https://doi.org/10.1016/j.biopsych.2017.08.008

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free