This analysis and post mortem sample size with replicates is noteworthy for an adequately powered sample to detect 1. 3 fold changes, improving sensitivity, reliability, and signal to noise issues. Previous smaller microarray studies have suggested that GABAA receptor subunits and glutamate related genes were differentially expressed in bipolar disorder and schizophrenia as well as in suicide completers associated with these disorders. We identified the up regula tion of gamma amino butyric acid A receptor, 5 subunit gene in suicide associated with bipolar disorder, confirming a previous report. The expres sion levels of two glutamate related genes, Glutamate ammonia ligase and glial high affinity glutamate transporter member 3 were decreased in suicide completers with schizophrenia.

The serotonergic and noradrenergic systems have been suggested to be associ ated with suicide. However, no genes related to these two neurotransmitter systems were identified, consistent with a previous report. This negative finding may sug gest indirect effects on these neurotransmitter systems. Genetic linkage studies have identified several loci associ ated with suicidal behaviors in bipolar disorders. Signifi cant and suggestive linkages for suicide were mapped on chromosome 2, 5, and 10 from 162 bipolar pedigrees. Among this studys suicide candidate genes associ ated with bipolar disorder, the tripartite motif containing 23 gene is located close to the significantly linked D5S1725 marker on chromosome 5. Another large scale genetic linkage study for bipolar disorder using 1060 individuals identified linkage on chromosome 10q25.

3 for suicide attempts. The microarray differentially expressed candidate gene EMX2 is included in this region of interest. Therefore, these two genes may be apt for future genetic association studies for suicide associated with bipolar disorder, proving causation. While this reanalysis study has the strengths of a larger sample size, independent replicates, and well character ized patient samples from specific areas of cortex, the find ing should be interpreted cautiously as this study has some Batimastat limitations. First, the mixed cellular nature of the brain samples might lower sensitivity due to dilutional effects as opposed to pure neuronal cells of a specific cor tical layer.

In general, most microarray studies with post mortem brain tissues find fold changes of less than 2 Differentially expressed genes between suicide completer vs fold, including this study. Second, although smoking, alcohol, and drug abuse were measured as confounding factors, all possible unmeasured, confounding variables for suicide cannot be formally excluded, such as severity of illness, personality traits, hopelessness, agitation, depres sive symptoms, and stress. Third, these findings are correlational and not causal. Fourth, these gene lists Distribution schizophreniaexpressed genes biological processvs.