Patterns of gene expression in the limbic system of suicides with and without major depression

Abstract

The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

Suicide and the Polyamine System

“…In addition to SAT1, other genes active during polyamine catabolism were also investigated. Gene expression levels of SAT2, an acetyltransferase that shares identity and homology with SAT1 [53], and ornithine aminotransferase-like 1, involved in the production of ornithine, were both found to be increased in the hippocampus of suicide completers [54]. In addition, the expression levels of spermine oxidase (SMOX) and spermine synthase (SMS), enzymes responsible, respectively, for the breakdown and synthesis of spermine, were altered in suicide completers.…”

The 2009 Nobel conference on the role of genetics in promoting suicide prevention and the mental health of the population

“…The first talk (Gustavo Turecki; McGill University, Canada) showed the utility of genome-wide expression studies, 13 here presenting a novel strategy for dealing with genetic heterogeneity by using an Extreme Value Analysis (EVA), examining genes in top 5% and with > 3-fold change in gene expression over 17 different brain regions in subgroups of suicides. Results showed reduction in mainly astrocytic gap junction genes GJA1 and GJB6, and transcription factor SOX9, among B20% of the suicides.…”

Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders

“…Numerous postmortem studies have shown abnormalities of histology, morphometry, neurochemistry and gene expression in the hippocampus of people with schizophrenia, 1-3 bipolar disorder [4][5][6] and depression. 5,[7][8][9] Individuals with schizo phrenia have shown hippocampal hypofunctionality with simultaneous prefrontal cortex hyperactivation during episodic memory retrieval tasks. 10,11 Moreover, functional neuroimaging reveals a connection between overactivation of the hippocampus and the positive psychotic symptoms of schizophrenia, such as hallucinations and delusions.…”