Increased protein and mRNA expression of resistin after dexamethasone administration.

Synthetic glucocorticoids such as dexamethasone are widely used to treat a variety of inflammatory and autoimmune conditions, but they may induce adverse events including hyperglycemia. To shed light on the effect and action mechanism of dexamethasone, we examined the alterations of gene expression levels caused by dexamethasone.Microarray analysis was performed on whole blood collected from 24 physically healthy subjects at baseline and after dexamethasone administration. The expression levels of resistin mRNA were found to be significantly increased after the dexamethasone administration. In a separate sample of 12 subjects, we examined plasma resistin protein levels and found that they were increased after dexamethasone administration. Furthermore, the plasma mRNA and protein levels of resistin were significantly higher in individuals who carried the A allele of RETN single nucleotide polymorphism rs3219175 than in those who did not carry the allele. There was no significant interaction between the genotype and dexamethasone administration. No significant correlation was found between plasma levels of cortisol and resistin. Consistent with previous studies, the genotype of RETN rs3219175 was a strong determinant of resistin levels. The present study showed that oral administration of dexamethasone increases the protein and mRNA levels of resistin irrespective of the rs3219175 genotype.

Possible association of CUX1 gene polymorphisms with antidepressant response in major depressive disorder.

Association between response to antidepressant treatment and genetic polymorphisms was examined in two independent Japanese samples of patients with major depressive disorder (MDD). Genome-wide approach using the Illumina Human CNV370-quad Bead Chip was utilized in the analysis of the 92 MDD patients in the first sample. In all, 11 non-intergenic single-nucleotide polymorphisms with uncorrected allelic P-value <0.0001 were selected for the subsequent association analyses in the second sample of 136 MDD patients. Difference in allele distribution between responders and nonresponders were found in the second-stage sample for rs365836 and rs201522 of the CUX1 gene (P=0.005 and 0.004, respectively). The allelic P-values for rs365836 and rs201522 in both samples combined were 0.0000023 and 0.0000040, respectively. Our results provide the first evidence that polymorphisms of the CUX1 gene may be associated with response to antidepressant treatment in Japanese patients with MDD.

Moderating effect of schizotypy on the relationship between smoking and neurocognition.

PURPOSE: Smoking rates in schizotypic individuals are shown to be elevated, as in patients with schizophrenia, although findings on the association of smoking with different symptomatology of schizotypy have been mixed. Moreover, possible moderating effects of schizotypy on the relationship between smoking and cognition have not been well documented. SUBJECTS AND METHODS: The Schizotypal Personality Questionnaire (SPQ) and the full version of the Wechsler Memory Scale-Revised (WMS-R) were administered to 501 healthy adults. Subjects were divided into smokers (n=85) and non-smokers (n=416) based on the presence/absence of current smoking. RESULTS: The analysis of covariance (ANCOVA) on the three factor scores as well as the total score of the SPQ, controlling for age and gender, revealed that cognitive-perceptual factor was significantly associated with an increased rate of smoking (P=0.048). The ANCOVA on the WMS-R indices, with smoking group as a fixed factor and age, gender and total SPQ score as covariates, revealed that the schizotypy-by-smoking interaction was significant for attention/working memory (P=0.029). DISCUSSION AND CONCLUSION: Positive schizotypy may be associated with more smoking. Schizotypy and smoking could interact with each other to negatively affect attention/working memory.

13C-phenylalanine breath test detects altered phenylalanine kinetics in schizophrenia patients.

Phenylalanine is an essential amino acid required for the synthesis of catecholamines including dopamine. Altered levels of phenylalanine and its metabolites in blood and cerebrospinal fluid have been reported in schizophrenia patients. This study attempted to examine for the first time whether phenylalanine kinetics is altered in schizophrenia using L-[1-(13)C]phenylalanine breath test ((13)C-PBT). The subjects were 20 chronically medicated schizophrenia patients (DSM-IV) and the same number of age- and sex-matched controls. (13)C-phenylalanine (99 atom% (13)C; 100 mg) was administered orally and the breath (13)CO(2) /(12)CO(2) ratio was monitored for 120 min. The possible effect of antipsychotic medication (risperidone (RPD) or haloperidol (HPD) treatment for 21 days) on (13)C-PBT was examined in rats. Body weight (BW), age and diagnostic status were significant predictors of the area under the curve of the time course of Δ(13)CO(2) (‰) and the cumulative recovery rate (CRR) at 120 min. A repeated measures analysis of covariance controlled for age and BW revealed that the patterns of CRR change over time differed between the patients and controls and that Δ(13)CO(2) was lower in the patients than in the controls at all sampling time points during the 120 min test, with an overall significant difference between the two groups. Chronic administration of RPD or HPD had no significant effect on (13)C-PBT indices in rats. Our results suggest that (13)C-PBT is a novel laboratory test that can detect altered phenylalanine kinetics in chronic schizophrenia patients. Animal experiments suggest that the observed changes are unlikely to be attributable to antipsychotic medication.

Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation.

OBJECTIVE: Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. This study was aimed to examine several brain chemical mediators, including Glx (glutamate + glutamine), using (1)H magnetic resonance spectroscopy (MRS) in medicated patients with schizophrenia, with and without psychotic exacerbation. METHOD: (1)H MRS was acquired in 24 patients with schizophrenia, with psychotic exacerbation; 22 patients without exacerbation; and 27 age- and sex-matched healthy volunteers. The levels of metabolites were measured in the left frontal and inferior parietal white matter and compared across the three groups. RESULTS: The Glx level was significantly elevated in the left inferior parietal white matter in the patients with psychotic exacerbation in comparison with that in the healthy volunteers and the patients without exacerbation (P < 0.05). We also detected that there was a significant correlation between Positive and Negative Syndrome Scale-positive scale and Glx level in the left parietal white matter (r = 0.51, P < 0.001). CONCLUSION: Higher than normal Glx levels indicate glutamatergic overactivity in the left inferior parietal white matter with schizophrenic exacerbation, a finding that is in accordance with the glutamatergic hypothesis in schizophrenia. The Glx level measured by (1)H MRS could be a biomarker for exacerbation in schizophrenia.