TY - JOUR T1 - Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression A1 - Sequeira, Adolfo A1 - Mamdani, Firoza A1 - Ernst, Carl A1 - Vawter, Marquis P. A1 - Bunney, William E. A1 - Lebel, Veronique A1 - Rehal, Sonia A1 - Klempan, Tim A1 - Gratton, Alain A1 - Benkelfat, Chawki A1 - Rouleau, Guy A. A1 - Mechawar, Naguib A1 - Turecki, Gustavo Y1 - 2009/08/11 N2 - Background Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations. Methodology/Principal Findings We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data. Conclusions/Significance The observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions. JF - PLOS ONE JA - PLOS ONE VL - 4 IS - 8 UR - https://doi.org/10.1371/journal.pone.0006585 SP - e6585 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0006585 ER -