Gene Expression Profiling of Depression and Suicide in Human Prefrontal Cortex

Sibille, Etienne; Arango, Victoria; Galfalvy, Hanga; Pavlidis, Paul; Erraji-Benchekroun, Loubna; Ellis, Steven P.; Mann, J. John

doi:10.1038/sj.npp.1300335

Cited by 106 publications

(88 citation statements)

References 41 publications

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“…Finally, two genes were confirmed as overexpressed in the non-depressed suicide when compared to the controls: ADCY8 (microarray FC = 1.46, RT FC = 1.62) and APLP2 (microarray FC = 1.35, RT FC = 1.33). Overall, as seen in other studies using microarrays and brain tissue, 51 correlations between relative fold changes seen using microarray and real-time analyses for the seven genes were good (mean R = 0.377, s.d. = 0.179).…”

Section: Nosupporting

confidence: 81%

“…36,37,58,59 Few studies have explored global expression changes between groups of suicides and psychiatrically normal controls, some have however focused on a particular psychiatric diagnosis, such as bipolar disorder or schizophrenia, and included within these groups subjects that died by suicide. [60][61][62][63][64][65][66][67] Sibille et al 51 recently compared expression patterns in BA9 and BA47 of depressed suicides versus psychiatrically normal controls matched on the basis of sex, age, DAVID genes correspond to the total number of unique DAVID annotated genes. The percentage represents the number of differentially expressed genes belonging to a given category over the total number of DAVID annotated genes.…”

Section: Discussionmentioning

confidence: 99%

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Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. 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 confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

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Section: Nosupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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“…Both the initial 'present' gene sets and those considered significant in data analysis were subjected to PCA. Analysis of gene ontology (GO) was carried out for differentially expressed genes using the gene score resampling (GSR) method in ErmineJ (v2.1.7), 10 with full resampling of ANOVA P-values and 200 000 iterations in P-value estimation for false discovery rate correction.…”

Section: Discussionmentioning

confidence: 99%

“…10 While 163 genes were categorized as differentially expressed in this region for our study, we opted not to use stringent correction procedures in the initial analysis. Rather, we see microarray studies as a hypothesis-generating tool, with the strength and validity of findings resting on finding consistency and independent sample validation, criteria used in this study, as well as the accumulated body of evidence from additional studies and complementary approaches.…”

Section: Discussionmentioning

confidence: 99%

“…In comparison with microarray studies of schizophrenia and bipolar disorder, only a handful of studies have been reported on gene expression changes associated with major depression and completed suicide. [8][9][10] There is a clear need for further investigation of the gene expression changes associated with these phenotypes to gain better insight into their possible biological mechanisms. 11 We have carried out a microarray-based investigation of these brain regions in both depressed and nondepressed suicide victims in comparison with controls, to identify novel candidate systems and biological pathways that may be involved in suicide and major depression.…”

Section: Introductionmentioning

confidence: 99%

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Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

et al. 2007

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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.

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Implication of SSAT by Gene Expression and Genetic Variation in Suicide and Major Depression

Sequeira¹,

Gwadry²,

Ffrench‐Mullen³

et al. 2006

Arch Gen Psychiatry

164

146

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Gene Expression Profiling of Depression and Suicide in Human Prefrontal Cortex

Cited by 106 publications

References 41 publications

Patterns of gene expression in the limbic system of suicides with and without major depression

Patterns of gene expression in the limbic system of suicides with and without major depression

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

Implication of SSAT by Gene Expression and Genetic Variation in Suicide and Major Depression

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