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Biol Psychiatry. 2018 Jan 1;83(1):81-89. doi: 10.1016/j.biopsych.2017.08.008. Epub 2017 Aug 18.

Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder.

Author information

1
Campbell Family Mental Health Research Institute of the Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
2
Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
3
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
4
Campbell Family Mental Health Research Institute of the Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: etienne.sibille@camh.ca.

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.

KEYWORDS:

Bioinformatics; Major depressive disorder; Mass spectrometry; Progressive neuropathologies; Remission; Subgenual cingulate cortex

PMID:
28935211
PMCID:
PMC5705452
DOI:
10.1016/j.biopsych.2017.08.008
[Indexed for MEDLINE]
Free PMC Article

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