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Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder.
- Source :
-
Biological psychiatry [Biol Psychiatry] 2018 Jan 01; Vol. 83 (1), pp. 81-89. Date of Electronic Publication: 2017 Aug 18. - Publication Year :
- 2018
-
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.<br />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.<br />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).<br />Conclusions: Collectively, the results provide evidence for persistent MDD effects across current episodes or remission, in the absence of detectable progressive neuropathology.<br /> (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Blotting, Western
Chromatography, Liquid
Cohort Studies
Depressive Disorder, Major drug therapy
Depressive Disorder, Major pathology
Disease Progression
Female
Gyrus Cinguli pathology
Humans
Male
Mass Spectrometry
Middle Aged
Proteomics
Depressive Disorder, Major metabolism
Gyrus Cinguli metabolism
Proteome
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2402
- Volume :
- 83
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biological psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 28935211
- Full Text :
- https://doi.org/10.1016/j.biopsych.2017.08.008