Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression

作者：Adolfo Sequeira, Firoza Mamdani, Carl Ernst, Marquis P. Vawter, William E. Bunney, Véronique Lebel, Sonia Rehal, Tim Klempan, Alain Gratton, Chawki Benkelfat, Guy A. Rouleau, Naguib Mechawar, Gustavo Turecki · 发表于：PLoS ONE · 年份：2009 · DOI：10.1371/journal.pone.0006585 · 被引用次数：398 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Tryptophan and brain disorders、Suicide and Self-Harm Studies

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 R...