engleski

The association of brain-derived neurotrophic factor (BDNF) Val66Met or catechol-o-methyltransferase (COMT) Val158Met polymorphism with antipsychotic-induced treatment response in schizophrenic patients

Schizophrenia is chronic psychiatric disorder, frequently associated with treatment resistance. Pharmacogenetics might help in selection of the adequate treatment for an individual patient. We evaluated the association of brain-derived neurotrophic factor (BDNF Val66Met) or catechol-o-methyltransferase (COMT Val158Met) polymorphisms with treatment response in 446 patients with schizophrenia (diagnosis made with SCID based on DSM-IV criteria). Patients received olanzapine (N=214) 10-20 mg/day, risperidone (N=111) 3-6 mg/day and clozapine (N=121) 100-500 mg/day. Response to antipsychotic drugs was defined as reduction in Positive and Negative Syndrome Scale (PANSS) scores after 8 weeks compared to baseline scores. The results, evaluated with χ2 test, analysis of variance and Tukey’s test, revealed that COMT Val158Met polymorphism was not significantly associated with response to olanzapine, risperidone or clozapine, while BDNF Val66Met polymorphism was not related to risperidone or clozapine response after 8 weeks of treatment. BDNF Val66Met polymorphism was significantly associated with response to olanzapine, since patients subdivided according to the Met/Met, Met/Val and Val/Val genotype (F=4.034 ; p=0.019), or Met carriers (the combined Met/Met and Val/Met genotype) and Val/Val homozygotes (F=4.034 ; p=0.019) had significantly different PANSS positive scores, and Met carriers and Val/Val homozygotes had significantly (F=4.080 ; p=0.045) different total PANSS scores. BDNF Met carriers had lower reduction in PANSS scores and poorer response to olanzapine treatment than Val/Val homozygotes, while responders had more frequently Val/Val genotype and responded better to olanzapine treatment than Met carriers. These findings suggest that genotyping of BDNF Val66Met might be used to differentiate responders and non-responders in schizophrenia.

brain-derived neurotrophic factor; BDNF Val66Met; catechol-o-methyltransferase; COMT Val158Met; polymorphisms; treatment response; schizophrenia

nije evidentirano