Putative psychosis genes in the prefrontal cortex: combined analysis of gene expression microarrays

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown similarities between schizophrenia and bipolar disorder in phenotypes and in genotypes, and those studies have contributed to an ongoing re-evaluation of the traditional dichotomy between schizophrenia and bipolar disorder. Bipolar disorder with psychotic features may be closely related to schizophrenia and therefore, psychosis may be an alternative phenotype compared to the traditional diagnosis categories.</p> <p>Methods</p> <p>We performed a cross-study analysis of 7 gene expression microarrays that include both psychosis and non-psychosis subjects. These studies include over 400 microarray samples (163 individual subjects) on 3 different Affymetrix microarray platforms.</p> <p>Results</p> <p>We found that 110 transcripts are differentially regulated (p < 0.001) in psychosis after adjusting for confounding variables with a multiple regression model. Using a quantitative PCR, we validated a set of genes such as up-regulated metallothioneins (MT1E, MT1F, MT1H, MT1K, MT1X, MT2A and MT3) and down-regulated neuropeptides (SST, TAC1 and NPY) in the dorsolateral prefrontal cortex of psychosis patients.</p> <p>Conclusion</p> <p>This study demonstrates the advantages of cross-study analysis in detecting consensus changes in gene expression across multiple microarray studies. Differential gene expression between individuals with and without psychosis suggests that psychosis may be a useful phenotypic variable to complement the traditional diagnosis categories.</p

The role of prostaglandins in chemically induced inflammation.

Dye leakage in rats, produced by intracutaneous injections of irritants into the abdominal skin, was quantitated using the Evans blue technique of Harada et al. (1971). In control rats and in rats pretreated with indomethacin (an inhibitor of prostaglandin synthesis) concentration-response lines were obtained for 5-hydroxytryptamine, histamine, bradykinin and prostaglandin E1, bradykinin in the presence of prostaglandin E1 (10-6 M), adenosine-5'-triphosphate, compound 48/80, capsaicin and silver nitrate. In rats pretreated with indomethacin the dye leakage responses to histamine, prostaglandin E1, adenosine-5'-triphosphate and silver nitrate were significantly reduced, but no significant changes were observed in the responses to the other irritants. It is suggested that part of the action of histamine, adenosine-5'-triphosphate and prostagland in E1 is produced indirectly by releaseor stimulation of the synthesis of prostaglandins or their precursors. These results might have important implications in the understanding of the inflammatory response

The effects of bradykinin and prostaglandin E1 on rat cutaneous afferent nerve activity.

1 The activity produced by intra-arterial bradykinin and prostaglandin E1 was investigated in multifibre strands dissected from the saphenous nerves of anaesthetized rats. 2 Bradykinin (0.5-10mug) alone produced little activity in nerve strands but produced considerable activity following a 10 min infusion, but not a single injection, of prostaglandin E1 (5-100 ng). 3 Prostaglandin E, alone produced a few large height spikes but following several injections of bradykinin smaller height spikes were also produced by prostaglandin E1. 4 It was concluded that the presence of a low concentration of prostaglandin E, is required for bradykinin to manifest its actions and that bradykinin and prostaglandin E1 are mutually potentiating in their effects on afferent nerve terminals

The effect of baclofen on the cardiovascular system of the rat.

1 The cardiovascular responses to baclofen were investigated in anaesthetized rats. 2 Low doses of baclofen (less than 5 X 10(-8) mol), given intravenously, produced a transient fall in blood pressure and heart rate. Higher doses (greater than 5 X 10(-7) mol) produced a marked and prolonged increase in blood pressure accompanied by a rise in heart rate and cutaneous arterial dilatation. 3 The pressor and heart rate responses exhibited tachyphylaxis, and were abolished by hexamethonium, cervical cord section, reserpine-treatment and by a combination of alpha- and beta-adrenoceptor antagonists. 4 It is concluded that the increases in blood pressure and heart rate produced by high doses of baclofen are of central sympathetic origin