Identification of commonly altered genes between in major depressive disorder and a mouse model of depression

Abstract

The heterogeneity of depression (due to factors such as varying age of onset) may explain why biological markers of major depressive disorder (MDD) remain uncertain. We aimed to identify gene expression markers of MDD in leukocytes using microarray analysis. We analyzed gene expression profiles of patients with MDD (age ≥50, age of depression onset <50) (N = 10, depressed state; N = 13, remitted state). Seven-hundred and ninety-seven genes (558 upregulated, 239 downregulated when compared to those of 30 healthy subjects) were identified as potential markers for MDD. These genes were then cross-matched to microarray data obtained from a mouse model of depression (676 genes, 148 upregulated, 528 downregulated). Of the six common genes identified between patients and mice, five genes (SLC35A3, HIST1H2AL, YEATS4, ERLIN2, and PLPP5) were confirmed to be downregulated in patients with MDD by quantitative real-time polymerase chain reaction. Of these genes, HIST1H2AL was significantly decreased in a second set of independent subjects (age ≥20, age of onset <50) (N = 18, subjects with MDD in a depressed state; N = 19, healthy control participants). Taken together, our findings suggest that HIST1H2AL may be a biological marker of MDD.

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

“…We have detected differentially interacting proteins by comparing data sets from the hippocampus and the CA3 subfield of the hippocampus. All the CA3 (PSD95-cTAP; Grik4 Cre) enriched proteins (Abr, Actn4, Bai3, Cacng8, Grik2, Hist1h2al, Mbp, Nlgn3 and Prdx5) have been reported to have important functions in brain that include roles in synapse formation, synaptic plasticity and psychiatric disorders (Duman, Tu, & Tolias, 2016;Ge et al, 2016;Kalinowska et al, 2015;Lanoue et al, 2013;Malty et al, 2017;Martinelli et al, 2016;Oh et al, 2010;Park et al, 2017;Sigoillot et al, 2015;Walikonis et al, 2001;Yamagata et al, 2017). This might indicate that different types of PSD95 complexes exist in different brain regions with distinct functions.…”

Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder

“…Previously, a gene expression analysis in depressed patients further replicated in mice found lower levels of YEATS4 in depressed patients compared to healthy controls. Moreover, the expression level of this gene was correlated with the dose of imipramine (a tricyclic antidepressant) ( 56 ).…”

Epigenetic mechanisms of major depression: Targeting neuronal plasticity

“…7,[24][25][26] The pathophysiology of MDD and response to antidepressants are suggested to be controlled by epigenetic modulation of transcription. 7,24,25,27 Epigenetics refers to multiple processes that can induce both transient and potentially heritable lasting changes in gene expression. Epigenetic mechanisms alter the affinity of genomic DNA for various regulatory proteins and/or the association of genomic DNA with proteins that maintain the higher-order structure of the chromosome (e.g., chromatin remodeling).…”

“…Indeed, disruptions in transcription occur in various brain areas in preclinical models of depression and in MDD patients . The pathophysiology of MDD and response to antidepressants are suggested to be controlled by epigenetic modulation of transcription . Epigenetics refers to multiple processes that can induce both transient and potentially heritable lasting changes in gene expression.…”