Improvement of prefrontal brain function in endogenous psychoses under atypical antipsychotic treatment.

Typical and atypical antipsychotics are thought to exert their effects on different neurotransmitter pathways with specific action of atypical compounds on the prefrontal cortex, but studies directly investigating the effect of those drugs on neurophysiological measures of prefrontal brain function are sparse. We therefore investigated the influence of different antipsychotics on an electrophysiological marker of prefrontal brain function (NoGo anteriorization, NGA) and neuropsychological test scores. For this purpose, 38 patients with endogenous psychoses were investigated at the beginning of a stationary psychiatric treatment and at a 6-week-follow-up. Patients were treated with typical or atypical antipsychotics, or a combination of both. They underwent psychopathological diagnostic and neuropsychological testing, as well as electrophysiological investigations during a Continuous Performance Test. The results indicate that typical and atypical antipsychotics differentially affected the development of the NGA over the course of the treatment, typical antipsychotics tending to result in decreased values at follow-up, and atypical antipsychotics stabilizing, or increasing this parameter. Performance in tests of frontal lobe function generally declined under typical antipsychotics and improved with atypical compounds, changes in Stroop interference correlated with changes in the NGA. We conclude that typical and atypical antipsychotics differ regarding their effect on prefrontal brain function in schizophrenia, atypical neuroleptics often showing a more favorable impact than conventional antipsychotics on respective parameters.

Is FKBP5 a genetic marker of affective psychosis? A case control study and analysis of disease related traits.

BACKGROUND: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important pathogenic factor in depression. Genetic variants of FKBP5, a protein of the HPA system modulating the glucocorticoid receptor, have been reported to be genetically associated with improved response to medical treatment and an increase of depressive episodes. METHODS: We examined three single nucleotide polymorphisms (SNPs) in FKBP5, rs4713916 in the proposed promoter region, rs1360780 in the second intron and rs3800373 in the 3'-untranslated region (3'-UTR), in a case-control study of Caucasian origin (affective psychosis: n = 248; controls: n = 188) for genetic association and association with disease related traits. RESULTS: Allele and genotype frequencies of rs4713916, rs1360780 and rs3800373 were not significantly different between cases and controls. Two three-locus haplotypes, G-C-T and A-T-G, accounted for 86.2% in controls. Odds ratios were not increased between cases and controls, except the rare haplotype G-C-G (OR 6.81), representing 2.1% of cases and 0.3% of controls. The frequency of rs4713916AG in patients deviated from expected Hardy-Weinberg equilibrium, the genotype AA at rs4713916 in monopolar depression (P = 0.011), and the two-locus haplotype rs1360780T--rs3800373T in the total sample (overall P = 0.045) were nominally associated with longer continuance of disease. CONCLUSION: Our data do not support a significant genetic contribution of FKBP5 polymorphisms and haplotypes to affective psychosis, and the findings are inconclusive regarding their contribution to disease-related traits.

Analysis of GABRB2 association with schizophrenia in German population with DNA sequencing and one-label extension method for SNP genotyping.

OBJECTIVES: Schizophrenia (SCZ) is a complex mental disease that affects approximately 1% of the population. In this study, six SNPs in GABRB2 were genotyped for a case-control association study with the cycloid psychosis subtype of SCZ in the German population using two methods for SNP genotyping. DESIGN AND METHODS: The SNPs were genotyped by direct DNA sequencing, as well as a novel one-label extension method. The results were analyzed for association with SCZ. RESULTS AND CONCLUSIONS: Significant association was found for SNPs rs1816071 and rs1816072 with SCZ susceptibility. This is consistent with our previous finding of association of SNPs in GABRB2 with SCZ susceptibility in Han Chinese. There was a total agreement between the genotyping results from one-label extensions and the results of direct DNA sequencing, thus validating the accuracy of the one-label extension method of SNP genotyping.

Sensory gating deficit in a subtype of chronic schizophrenic patients.

The dual click P50 paradigm has been established as a neurophysiological method to detect gating mechanisms. Studies of schizophrenic patients have shown that an insufficient reduction of the P50 amplitude after the second relative to the first stimulus indicates a deficient sensory gating mechanism. The aim of this study was to compare the P50 responses in the dual click paradigm of healthy volunteers to those of patients with different psychotic disorders, especially with regard to psychopathology and nosology according to ICD-10 and DSM-IV and to the classification system of Leonhard. A total of 34 patients and 12 healthy volunteers were investigated electrophysiologically while they performed the P50 dual click experiment. Patients with prominent negative symptoms and without perceptual abnormalities and patients with a hebephrenic subtype of schizophrenia showed less suppression in the dual click P50 paradigm than did healthy controls. Patients with brief/acute and transient psychotic disorders or cycloid psychoses did not differ from healthy volunteers with regard to suppression in the dual click P50 paradigm. No striking influence of gender, age, duration of disease and present medication was found. The findings confirm the lack of sensory gating measured by the dual click P50 paradigms in some but not all patients with schizophrenia. Both subtype of schizophrenia and current form of psychopathology appear to be related to the presence or absence of abnormal sensory gating.

Postpartum psychoses: prognosis, risk factors, and treatment.

Puerperal psychoses do not represent a nosological entity, but rather a selection of puerperally triggered "ordinary" functional psychoses with cycloid psychoses predominating and schizophrenias occurring very rarely. The prognosis is basically favorable concerning symptom remission and social and occupational functioning. However, there is a considerable frequency of relapses and an increased suicide rate. The most important risk factors for an episode of a puerperal psychosis are being primiparous and having suffered a previous episode of a psychosis, particularly a cycloid psychosis. Controlled treatment studies up to now are absent. Case studies suggest in acute episodes the efficacy of a symptom-oriented pharmacologic treatment where ablactation is recommended. With respect to prophylactic treatment some authors propose to apply lithium in late pregnancy or immediately after delivery. Because of its possible teratogenic effects and the altogether rather sparse data, the authors however cannot recommend the use of lithium during pregnancy. Applying estradiol after delivery may be beneficial and safe, but further studies are necessary to clarify these issues.