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BACKGROUND: One of the key risk factors for relapse in schizophrenia is poor insight. Genetic influences on poor insight have not yet been studied despite growing evidence to the extent of genetic contributions in schizophrenia. There is evidence of genetic associations for psychopathology symptom domains (Arnedo et al., 2015) and these domains are strongly associated with insight. Dysfunction of the catechol-O-methyltransferase (COMT) gene is shown to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. COMT Val allele more rapidly inactivates released dopamine than the Met allele, and is shown to be associated with cognitive performance such as working memory and attention, and influences ToM functioning by modulating the dopamine pathways. Since the role of COMT in schizophrenia remains questionable, we determined whether any association exists between COMT genotypes and clinical symptomatology (Lack of Insight and Judgment) in a large cohort of schizophrenia subjects. METHODS: 145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling. Subjects were evaluated on clinical symptoms (PANSS). Genotyping of the COMT Val158Met polymorphism was evaluated compared to PANSS Marder factors, including PANSS items Lack of Insight and Judgment. RESULTS: Of 145 subjects, data from 138 subjects were usable. Distribution of COMT genotype: Met/Met: 28 (20.29%), Val/Met: 61 (44.20%), and Val/Val: 49 (35.51%). There was no significant difference between mean PANSS total score Met/Met: 76.053 (SD 13.011), Met/Val: 78.001 (SD 12.489), Val/Val: 79.596 (SD 11.286). Patients with the COMT Val/Val genotype had significantly higher total score on the PANSS Item Lack of Insight than those with the Val/Met or Met/Met genotypes (p = 0.041). Patients with the COMT Val/Val genotype also had significantly higher scores on the PANSS Disorganized Factor than those with the COMT Val/Met genotype (p = 0.043). As an exploratory analysis, COMT Val/Met showed significant association with Blunted Affect (p = 0.039), but no other items of the negative symptom factor. DISCUSSION: Our findings support hypotheses regarding associations between COMT polymorphisms and lack of insight and judgment in schizophrenia. It is important that the exact mechanisms of genetic contribution to insight are delineated to aid the development of effective treatments and to identify prevention strategies. |
