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COMT (Val158/108Met) genotype moderates the impact ofantipsychotic medication on verbal IQ in twins with schizophrenia

Rebollo-Mesa, Irenea,b; Picchioni, Marcoa,c; Shaikh, Madihaa; Bramon, Elviraa; Murray, Robina; Toulopoulou, Timotheaa

doi: 10.1097/YPG.0b013e32834371a7
Original Articles

Objectives In this study, we aimed to assess the moderating effects of the catechol-O-methyl transferase (COMT) (Val158/108Met) genotype on antipsychotic medication-induced changes in the cognitive performance of patients with chronic schizophrenia.

Methods The sample consisted of 85 monozygotic and53dizygotic twin pairs, of varying concordance for schizophrenia, and healthy control twins. Cognitive abilitywas measured using the Wechsler Adult Intelligence Scale-third edition. We used structural equation modelling to estimate main and interaction effects of the COMT status and antipsychotic medication dose on verbal intelligence quotient (VIQ) and performance intelligence quotient scores.

Results There was no evidence of a main or interaction effect of the COMT status or chlorpromazine equivalent dose on the performance intelligence quotient. There were no main effects of COMT or chlorpromazine equivalent dose on VIQ; however, there was evidence of a statistically significant interaction (P<0.01) between the COMT andchlorpromazine equivalents on VIQ. The VIQ performance ofval/val individuals was significantly lower with increasing antipsychotic medication dose, up to 12 intelligence quotient points lower than met carriers treated with medication. Intheabsence of medication, the three genotypes did not significantly differ, whereas at the highest doses (1500), the val/val homozygotes and Met carriers differed by morethan one standard deviation.

Conclusion Our results show that the verbal abilities ofval homozygotes of the COMT gene are cognitively impaired by higher doses of antipsychotic medication. Thisassociation is reversed in Met carriers. These data areconsistent with an earlier study that found evidence ofmoderating effects of antipsychotic medication onN-back and verbal fluency tasks.

aDivision of Psychological Medicine, Institute of Psychiatry, King's College London

bMRC Centre for Transplantation, King's College London, London

cSt Andrew's Academic, Institute of Psychiatry, Northampton, UK

Correspondence to Irene Rebollo-Mesa, PhD, MRC Centre for Transplantation, King's College London, 5th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE19RT, UK Tel: +44 20 7188 1524; fax: +44 20 7188 5660; e-mail:

Received May 14, 2010

Accepted November 15, 2010

© 2011 Lippincott Williams & Wilkins, Inc.