2008 Brain Star Award Recipient - P. Adolfo Sequeira
Recipient
P. Adolfo Sequeira - Biosketch
PhD Human Genetics
McGill University
Article
Patterns of gene expression in the limbic system of suicides with and without major depression. Sequeira A, Klempan T, Canetti L, ffrench-Mullen J, Benkelfat C, Rouleau GA, Turecki G. Mol Psychiatry. 2007 Jul;12(7):640-55
Significance of the paper
Suicide is a major public health problem and the leading cause of death for men younger than 35 years in Canada and with one million suicides worldwide estimated by the World Health Organization each year. This study aimed to identify new molecular targets playing a role in the neurobiology of suicide and depression in the limbic system, often associated with the control of emotions and with mood disorders but never studied before on a global comprehensive manner.
Differential expression in limbic regions (anterior (BA24) and posterior (BA29) cingulate cortex, amygdala and hippocampus) showed group-specific patterns of expression in suicide and depression. Gene ontology analysis revealed an overrepresentation of transcription and metabolic genes in the hippocampus and amygdala, whereas altered genes in the BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity. 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 pointed to global alteration of GABAergic neurotransmission in suicide and major depression.
Overall, these results suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicide and highlight the role of the hippocampus in major depression. This is the first global gene expression study of suicide and depression in the limbic system. The identification of GABAergic alterations, if confirmed, could lead to the development of biomarkers to facilitate the assessment of suicide risk and the prevention of suicide in major depression.