title: Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors: Adolfo
authors: A
authors: Sequeira
authors: Firoza
authors: F
authors: Mamdani
authors: Carl
authors: C
authors: Ernst
authors: Marquis P
authors: MP
authors: Vawter
authors: William E
authors: WE
authors: Bunney
authors: Veronique
authors: V
authors: Lebel
authors: Sonia
authors: S
authors: Rehal
authors: Tim
authors: T
authors: Klempan
authors: Alain
authors: A
authors: Gratton
authors: Chawki
authors: C
authors: Benkelfat
authors: Guy A
authors: GA
authors: Rouleau
authors: Naguib
authors: N
authors: Mechawar
authors: Gustavo
authors: G
authors: Turecki
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000235:genetics*; D020869:Gene Expression Profiling; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013405:Suicide; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid