Limits...
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.

Show MeSH

Related in: MedlinePlus

Distribution of gene ontology groups for biological process at level 4 of differentially expressed genes between suicide vs. non-suicide in schizophrenia cohorts.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2211497&req=5

Figure 2: Distribution of gene ontology groups for biological process at level 4 of differentially expressed genes between suicide vs. non-suicide in schizophrenia cohorts.

Mentions: Functional annotation of the differentially expressed genes by Gene Ontology indicated that 9 biological processes were significantly overrepresented (at level 4; P < 0.05) among the suicide candidate genes in the schizophrenia cohort (Fig. 2). The transport genes were the most commonly over-represented biological process in our suicide candidate gene list for schizophrenia, including the glial, high affinity, glutamate transporter (SLC1A3). In contrast, no significantly over-represented biological process group emerged with suicide candidate genes in the bipolar disorder group.


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)

Distribution of gene ontology groups for biological process at level 4 of differentially expressed genes between suicide vs. non-suicide in schizophrenia cohorts.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Distribution of gene ontology groups for biological process at level 4 of differentially expressed genes between suicide vs. non-suicide in schizophrenia cohorts.
Mentions: Functional annotation of the differentially expressed genes by Gene Ontology indicated that 9 biological processes were significantly overrepresented (at level 4; P < 0.05) among the suicide candidate genes in the schizophrenia cohort (Fig. 2). The transport genes were the most commonly over-represented biological process in our suicide candidate gene list for schizophrenia, including the glial, high affinity, glutamate transporter (SLC1A3). In contrast, no significantly over-represented biological process group emerged with suicide candidate genes in the bipolar disorder group.

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