Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression
- 16 October 2007
- journal article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 14 (2), 175-189
- https://doi.org/10.1038/sj.mp.4002110
Abstract
The prefrontal cortex is believed to play a major role in depression and suicidal behavior through regulation of cognition, memory, recognition of emotion, and anxiety-like states, with numerous post-mortem studies documenting a prefrontal serotonergic dysregulation considered to be characteristic of depressive psychopathology. This study was carried out to detect changes in gene expression associated with both suicide and major depression using oligonucleotide microarrays (Affymetrix HG-U133 chip set) summarizing expression patterns in primarily ventral regions of the prefrontal cortex (BA44, 45, 46 and 47). A total of 37 male subjects were included in this study, of which 24 were suicides (depressed suicides=16, nondepressed suicides=8) and 13 were matched controls. All subjects were clinically characterized by means of psychological autopsies using structured interviews. Unique patterns of differential expression were validated in each of the cortical regions evaluated, with group-specific changes highlighting the involvement of several key neurobiological pathways that have been implicated in both suicide and depression. An overrepresentation of factors involved in cell cycle control and cell division (BA44), transcription (BA44 and 47) and myelination (BA46) was seen in gene ontology analysis of differentially expressed genes, which also highlights changes in the expression of genes involved in ATP biosynthesis and utilization across all areas. Gene misexpression in BA46 was most pronounced between the two suicide groups, with many significant genes involved in GABAergic neurotransmission. The pronounced misexpression of genes central to GABAergic signaling and astrocyte/oligodendrocyte function provides further support for a central glial pathology in depression and suicidal behavior.Keywords
This publication has 49 references indexed in Scilit:
- Implication of SSAT by Gene Expression and Genetic Variation in Suicide and Major DepressionArchives of General Psychiatry, 2006
- Prominent Reduction in Pyramidal Neurons Density in the Orbitofrontal Cortex of Elderly Depressed PatientsBiological Psychiatry, 2005
- Association of 14-3-3 ε gene haplotype with completed suicide in JapaneseJournal of Human Genetics, 2005
- Gene Expression Profiling of Depression and Suicide in Human Prefrontal CortexNeuropsychopharmacology, 2003
- Familial Pathways to Early-Onset Suicide AttemptArchives of General Psychiatry, 2002
- Depression: Perspectives from Affective NeuroscienceAnnual Review of Psychology, 2002
- Suicidal behavior: is there a genetic predisposition?Bipolar Disorders, 2001
- The Neurobiology and Genetics of Suicide and Attempted Suicide: A Focus on the Serotonergic SystemNeuropsychopharmacology, 2001
- Lower3H-paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high affinity, non-transporter sitesJournal of Neural Transmission, 1996
- Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victimsBrain Research, 1995