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Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex.

Kim S, Choi KH, Baykiz AF, Gershenfeld HK - BMC Genomics (2007)

Bottom Line: Microarray studies with post-mortem prefrontal cortex (Brodmann's Area 46/10) tissue require larger sample sizes.Among bipolar samples, 13 genes were found and among schizophrenia samples, 70 genes were found as differentially expressed.By qRT-PCR, PLSCR4 and EMX2 were significantly down-regulated in the schizophrenia suicide completers, but could not be confirmed in bipolar disorder.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry, Univ, of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA. Howard.Gershenfeld@UTSouthwestern.edu.

ABSTRACT

Background: Suicide is an important and potentially preventable consequence of serious mental disorders of unknown etiology. Gene expression profiling technology provides an unbiased approach to identifying candidate genes for mental disorders. Microarray studies with post-mortem prefrontal cortex (Brodmann's Area 46/10) tissue require larger sample sizes. This study poses the question: to what extent are differentially expressed genes for suicide a diagnostic specific set of genes (bipolar disorder vs. schizophrenia) vs. a shared common pathway?

Results: In a reanalysis of a large set of Affymetrix Human Genome U133A microarray data, gene expression levels were compared between suicide completers vs. non-suicide groups within a diagnostic group, namely Bipolar disorder (N = 45; 22 suicide completers; 23 non-suicide) or Schizophrenia (N = 45; 10 suicide completers ; 35 non-suicide). Among bipolar samples, 13 genes were found and among schizophrenia samples, 70 genes were found as differentially expressed. Two genes, PLSCR4 (phospholipid scramblase 4) and EMX2 (empty spiracles homolog 2 (Drosophila)) were differentially expressed in suicide groups of both diagnostic groups by microarray analysis. By qRT-PCR, PLSCR4 and EMX2 were significantly down-regulated in the schizophrenia suicide completers, but could not be confirmed in bipolar disorder.

Conclusion: This molecular level analysis suggests that diagnostic specific genes predominate to shared genes in common among suicide vs. non-suicide groups. These differentially expressed, candidate genes are neural correlates of suicide, not necessarily causal. While suicide is a complex endpoint with many pathways, these candidate genes provide entry points for future studies of molecular mechanisms and genetic association studies to test causality.

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Ingenuity pathway analysis of EMX2 and differentially expressed suicide candidate genes in bipolar disorder (A) and schizophrenia (B).
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Figure 3: Ingenuity pathway analysis of EMX2 and differentially expressed suicide candidate genes in bipolar disorder (A) and schizophrenia (B).

Mentions: Additionally, we analyzed the list of differentially expressed genes for each diagnosis by the Ingenuity Pathways Analysis (IPA) software to identify biological pathways and networks. We identified distinct signaling networks from suicide candidate genes that included the EMX2 gene in both disorders (Fig. 3). In bipolar disorder, the pathway perspective suggested a signaling network related to both cellular movement and cell to cell signaling, with interactions encompassing 10 differentially expressed, suicide candidate genes (Fig. 3A). By contrast, in schizophrenia patients, the differentially expressed genes were related in a cell death signaling network (Fig. 3B).


Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex.

Kim S, Choi KH, Baykiz AF, Gershenfeld HK - BMC Genomics (2007)

Ingenuity pathway analysis of EMX2 and differentially expressed suicide candidate genes in bipolar disorder (A) and schizophrenia (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211497&req=5

Figure 3: Ingenuity pathway analysis of EMX2 and differentially expressed suicide candidate genes in bipolar disorder (A) and schizophrenia (B).
Mentions: Additionally, we analyzed the list of differentially expressed genes for each diagnosis by the Ingenuity Pathways Analysis (IPA) software to identify biological pathways and networks. We identified distinct signaling networks from suicide candidate genes that included the EMX2 gene in both disorders (Fig. 3). In bipolar disorder, the pathway perspective suggested a signaling network related to both cellular movement and cell to cell signaling, with interactions encompassing 10 differentially expressed, suicide candidate genes (Fig. 3A). By contrast, in schizophrenia patients, the differentially expressed genes were related in a cell death signaling network (Fig. 3B).

Bottom Line: Microarray studies with post-mortem prefrontal cortex (Brodmann's Area 46/10) tissue require larger sample sizes.Among bipolar samples, 13 genes were found and among schizophrenia samples, 70 genes were found as differentially expressed.By qRT-PCR, PLSCR4 and EMX2 were significantly down-regulated in the schizophrenia suicide completers, but could not be confirmed in bipolar disorder.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry, Univ, of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA. Howard.Gershenfeld@UTSouthwestern.edu.

ABSTRACT

Background: Suicide is an important and potentially preventable consequence of serious mental disorders of unknown etiology. Gene expression profiling technology provides an unbiased approach to identifying candidate genes for mental disorders. Microarray studies with post-mortem prefrontal cortex (Brodmann's Area 46/10) tissue require larger sample sizes. This study poses the question: to what extent are differentially expressed genes for suicide a diagnostic specific set of genes (bipolar disorder vs. schizophrenia) vs. a shared common pathway?

Results: In a reanalysis of a large set of Affymetrix Human Genome U133A microarray data, gene expression levels were compared between suicide completers vs. non-suicide groups within a diagnostic group, namely Bipolar disorder (N = 45; 22 suicide completers; 23 non-suicide) or Schizophrenia (N = 45; 10 suicide completers ; 35 non-suicide). Among bipolar samples, 13 genes were found and among schizophrenia samples, 70 genes were found as differentially expressed. Two genes, PLSCR4 (phospholipid scramblase 4) and EMX2 (empty spiracles homolog 2 (Drosophila)) were differentially expressed in suicide groups of both diagnostic groups by microarray analysis. By qRT-PCR, PLSCR4 and EMX2 were significantly down-regulated in the schizophrenia suicide completers, but could not be confirmed in bipolar disorder.

Conclusion: This molecular level analysis suggests that diagnostic specific genes predominate to shared genes in common among suicide vs. non-suicide groups. These differentially expressed, candidate genes are neural correlates of suicide, not necessarily causal. While suicide is a complex endpoint with many pathways, these candidate genes provide entry points for future studies of molecular mechanisms and genetic association studies to test causality.

Show MeSH
Related in: MedlinePlus