Sensory gating deficit is associated with catechol-O-methyltransferase polymorphisms in bipolar disorder

Abstract

Objectives. Recent studies have evidenced that bipolar patients show a sensory gating deficit (P50). Among the neural systems that could be influencing this electrophysiological phenotype, dopamine seems to play an important role. We hypothesize that catechol-O-methyltransferase (COMT), the main metabolizer of dopamine in prefrontal cortex, is related to this deficit. Methods. We selected three polymorphisms in COMT gene: rs2075507 (Promoter 2 region), Val158Met (rs4680) and rs165599 (3’ region). A case–control study was performed in 784 controls and 238 bipolar patients. Besides, 122 euthymic bipolar subjects and 95 healthy subjects carried out a sensory gating task (P50). Results. Polymorphism rs165599 in the COMT gene was associated with susceptibility to bipolar disorder (BD), mainly in women (AG: OR = 1.46; GG: OR = 1.84; P = 0.03). In the female group, haplotype AAG was associated with an OR = 7.6. Subjects who carried Val158 allele evidenced a deficit in suppression (P = 0.046) and rs165599 allele G carriers (mainly in homozygosis) had a bigger S2 amplitude and a higher S2/S1 ratio (1.6^e-5 < P < 0.01). Not a single association was proven in the control group. Conclusions. Our results support the association of the COMT gene with BD and with one of its potential endophenotypes, auditory sensory gating deficit, measured by the P50 paradigm.

Key words::

• Bipolar disorder
• sensory gating
• genetics
• catechol O-methyltransferase
• haplotypes

Acknowledgements

Support for the study was provided by the National Institute of Health Carlos III (FIS Exp. PI030544, FIS N° 060628.), the Mutua Madrileña Foundation and the Committee of Castilla la Mancha (Exp: 0316-02). I.A. has received a research grant from the Foundation for Biomedical Research of the Clínico San Carlos Hospital, Madrid (Spain). The authors would like to thank all patients for their participation in the study.

Statement of Interest

None to declare.