Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping.

The description of the heterogeneous phenomenological, pathophysiological, and etiological nature of schizophrenia is under way; however, the relationships between heterogeneity levels are still unclear. We performed a robust cross-sectional study, including a systematic neuropsychological battery, assessment of clinical symptoms, neurological soft signs, morphogenetic anomalies and smell identification, and measurement of event-related potentials on 50 outpatients with schizophrenia in their compensated states. An explorative fuzzy cluster analysis revealed two subgroups in this sample that could be distinguished from each other on symptomatological, cognitive and neurological levels. The patterns of cognitive dysfunctions and neurological developmental anomalies equally indicate that there may be hemispherical differences between the patients belonging to the different clusters.

Effects of a hypnotically altered state of consciousness on intensification of semantic processing.

In a study of the linguistic processes involved in hypnosis, 22 volunteer medical students performed semantic and phonologic fluency tasks and then associative priming tests with 2 delay-lengths in waking alert and hypnotic conditions as well. The participants performed better during semantic than phonological fluency tests in alert and also in hypnotic states, and this difference was significantly greater in hypnosis. The increased semantic performance in hypnosis was accompanied by a decrease of the rule-offending errors. Significant semantic priming effects were detected in both states of consciousness in direct and indirect relations as well as in the automatic, intralexical level, and also when the extralexical control processes were activated. Overall, the results appear to show that the hypnotically altered state of consciousness produces significantly better performance in semantic information processing than can be elicited in alert waking conditions.

Correlations between clinical symptoms, working memory functions and structural brain abnormalities in men with schizophrenia.

Thirteen male patients with schizophrenia and thirteen male normal control subjects were compared by magnetic resonance imaging (MRI) on volumes of the straight gyrus (SG), anterior cingulate gyrus, middle frontal gyrus, hippocampus, third ventricle, cavum septi pellucidi, total brain volume and intracranial volume. In addition, neuropsychological tasks were used to measure working memory and executive functions. Healthy volunteers and schizophrenic patients showed no significant differences in mean values for volumes of regions of interests. In the case of the SG, we found a significant difference in laterality: the tendency toward left dominance in healthy volunteers changed to significant right dominance in patients. The schizophrenic patients showed lower performance in working memory tasks, and strongly significant group differences were observed in measures of neurological signs assessed by the Neurological Evaluation Scale (NES). Negative symptoms correlated with the level of spatial working memory and executive functions. Negative symptoms also correlated with the volume of the right hippocampus, while the rate of anhedonia negatively correlated with the relative volume of the left SG.

Impact of venlafaxine on gene expression profile in lymphocytes of the elderly with major depression--evolution of antidepressants and the role of the "neuro-immune" system.

Antidepressive drugs offer considerable symptomatic relief in mood disorders and, although commonly discovered by screening with single biological targets, most interact with multiple receptors and signaling pathways. Antidepressants require a treatment regimen of several weeks before clinical efficacy is achieved in patient populations. While the biochemical mechanisms underlying the delayed temporal profile remain unclear, molecular adaptations over time are likely involved. The selective serotonin and noradrenaline reuptake inhibitor, venlafaxine, offers a dual antidepressive action. Its pharmacological behavior, however, is unknown at the genetic level, and it is difficult to monitor in human brain samples. Because the hypothalamic-pituitary-adrenal axis is often severely disrupted in mood disorders, lymphocytes may serve as models of neuropsychiatric conditions. As such, we examined the role of venlafaxine on the gene expression profile of human lymphocytes. DNA microarray was used to measure the expression patterns of multiple genes in human lymphocytes from depressed patients treated with this mood stabilizer. In this self-controlled study, RNAs of control and treated samples were purified, converted into cDNA and labeled with either Cy3 or Cy5, mixed and hybridized to DNA microarrays containing human oligonucleotides corresponding to more than 8,000 genes. Genes that were differentially regulated in response to treatment were selected for follow up on the basis on novelty, gene identity, and level of over-expression/repression, and selected transcripts were profiled by real-time PCR (data have been normalized to beta-actin). Using software analysis of the microarray data, a number of transcripts were differentially expressed between control and treated samples, of which only 57 were found to significantly vary with the "P" value of 0.05 or lower as a result of exposure to venlafaxine. Of these, 31 genes were more highly expressed and 26 transcripts were found to be significantly less abundant. Most selected genes were verified with QRT-PCR to alter. As such, independent verification using QRT-PCR demonstrated the reliability of the method. Genes implicated in ionic homeostasis were differentially expressed, as were genes associated with cell survival, neural plasticity, signal transduction, and metabolism. Understanding how gene expression is altered over a clinically relevant time course of administration of venlafaxine may provide insight into the development of antidepressant efficacy as well as the underlying pathology of mood disorders. These changes in lymphocytes are thought to occur in the brain, and a "neuro-immune system" is proposed by this study.