Psychosocial Functioning and Cognitive Deficits are Not Associated With Membrane-Bound Catechol-O-Methyltransferase Deoxyribonucleic Acid Methylation in Siblings of Patients With Schizophrenia

and †Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
The Journal of nervous and mental disease (Impact Factor: 1.69). 11/2012; 200(11):941-5. DOI: 10.1097/NMD.0b013e3182718c35
Source: PubMed


In this study, we investigated whether the siblings of patients with schizophrenia have deficits in cognition and psychosocial functioning and whether the psychosocial functioning and cognitive deficits correlate with the methylation status of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene in peripheral leukocytes. Cognitive abilities were evaluated using the attention/vigilance Continuous Performance Test, delayed/immediate recall scores, the Wisconsin Card Sorting Test, and the Semantic Verbal Fluency Test. Psychosocial functioning was evaluated using the Scale for the Assessment of Negative Symptoms, the Global Assessment of Functioning scale, and the Social Adjustment Scale. A bisulfate-based sequencing was adopted to analyze the methylation status of the MB-COMT promoter in peripheral leukocytes. Significant impairments in attention/vigilance and verbal memory and significant decreases in immediate and delayed recall scores were observed in the siblings of patients with schizophrenia compared with the healthy subjects. In addition, significant deficits in global social functioning and in social interaction were found in the siblings. The tested region of the MB-COMT promoter was generally unmethylated in peripheral leukocytes, without significant correlation with behavioral deficits in the siblings.Our study demonstrated that the siblings have significant deficits in cognition and psychosocial functioning, which may not be associated with MB-COMT methylation in peripheral leukocytes.

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    ABSTRACT: The serotoninergic system as a target for add-on treatment seems to be a promising approach in patients with schizophrenia. OBJECTIVE: To clarify if selective 5HT-6 antagonist AVN-211 (CD-008-0173) adds clinical and cognitive effects to stable antipsychotic treatment. METHODS: A randomized, double-blind, placebo-controlled, add-on, 4r-week trial in 47 schizophrenia patients (21 patients receiving study drug and 26 receiving placebo) who were stabilized on antipsychotic medication was performed. Seventeen patients from the study drug group and 25 patients from the placebo group completed the trial. Treatment effects were measured using clinical rating scales and attention tests. RESULTS: With no differences at baseline, there was a significant difference between the groups in Positive and Negative Syndrome Scale (PANSS) positive subscale score (p = 0.058) in favor of patients in the treatment group at the endpoint. The PANSS positive subscore (p = 0.0068) and Clinical Global Impression-Severity (CGI-S) (p = 0.048) score significantly changed only in the treatment group. Only in the placebo group were significant changes in Calgary Depression Rating Scale (CDRS) total score registered. The indices of attention tests at endpoint did not show differences between the groups, with the exception of the scope of change in the results of the subtest VIII of the Wechsler Adult Intelligence Scale (WAIS), which showed difference between the groups (p = 0.02) and was significantly larger in the treatment group. Only inside the study drug group, significant changes in selectivity and continuous attention were observed regarding total correct responses (p = 0.0038) and reaction time (p = 0.058) in the Continuous Attention Task (CAT) test. CONCLUSION: Selective 5HT6 antagonist AVN-211 (CD-008-0173) added antipsychotic and some procognitive (attention) effects to antipsychotic medication.
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