Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients

Abstract

Major depressive disorder (MDD) is a leading cause of disability worldwide and results tragically in the loss of almost one million lives in Western societies every year. This is due to poor understanding of the disease pathophysiology and lack of empirical medical tests for accurate diagnosis or for guiding antidepressant treatment strategies. Here, we have used shotgun proteomics in the analysis of post-mortem dorsolateral prefrontal cortex brain tissue from 24 MDD patients and 12 matched controls. Brain proteomes were pre-fractionated by gel electrophoresis and further analyzed by shotgun data-independent label-free liquid chromatography-mass spectrometry. This led to identification of distinct proteome fingerprints between MDD and control subjects. Some of these differences were validated by Western blot or selected reaction monitoring mass spectrometry. This included proteins associated with energy metabolism and synaptic function and we also found changes in the histidine triad nucleotide-binding protein 1 (HINT1), which has been implicated recently in regulation of mood and behavior. We also found differential proteome profiles in MDD with (n=11) and without (n=12) psychosis. Interestingly, the psychosis fingerprint showed a marked overlap to changes seen in the brain proteome of schizophrenia patients. These findings suggest that it may be possible to contribute to the disease understanding by distinguishing different subtypes of MDD based on distinct brain proteomic profiles.

The DSM5/RDoC debate on the future of mental health research: implication for studies on human stress and presentation of the signature bank

“…Consequently, the goal of RDoC is to define the basic dimensions of dysfunction that can cut across mental health disorders (for good examples of this approach, see Goodkind et al, 2015;Martins-de-Souza et al, 2012;Schwarz et al, 2012a,b). Contrary to the DSM5 that is a categorical (yes-no; presence versus absence of a disorder) system, the RDoC is a dimensional system that spans the range from normality to abnormality with continuous measures.…”

Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics

“…Detailed clinical and demographic information regarding these cohorts have been published previously. 16,17 The work described in this study was approved by the Human Research Ethics Committee at the University of Wollongong and conducted according to their guidelines (HE13/069).…”

“…These prior studies have an important limitation in that they do not distinguish between MDP and MDNP, particularly since differential proteome profiles have been recently reported, specifically between MDNP and MDP. 17 …”

Análise proteômica da esquizofrenia

“…The consistent differential expression of ALDOC, ENO2, HK1, PGAM1, TPI1 and GAPDH place Glycolysis as one of the main biochemical pathway for further studies, basic or clinical. Interestingly, this is not the most affected pathway found in the prefrontal cortex of depression brains but oxidative phosphorylation 15 .…”