¹Department of Neuroscience, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, USA

Correspondence: J John Mann, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA. Tel: +1 212 543 5571; Fax: +1 212 543 6017; E-mail: jjm@columbia.edu

Received 26 November 2001; Revised 20 May 2002; Accepted 29 May 2002.

Abstract

The 5-HT_1B receptor has been implicated in several psychopathologies, including pathological aggression, alcoholism and suicide. To test these and related potential genetic relationships in a single population, the human 5-HT_1B receptor (h5-HTR_1B) genotype for the G861C polymorphism was determined in 394 psychiatric patients and 96 healthy volunteers. Structured clinical interviews generated DSM III-R diagnoses. No significant association of the genotype or allele frequencies of the h5-HTR_1B G861C locus was observed with diagnoses of alcoholism, bipolar disorder, schizophrenia or a history of a suicide attempt. Exploratory analyses indicated an association of the genotype and allele frequencies of the h5-HTR_1B G861C locus with a history of substance abuse disorder (²=9.51, df=2, p=0.009; ²=7.31, df=1, p=0.007, respectively) and with a diagnosis of a major depressive episode (²=6.83, df=2, p=0.033; ²=5.81, df=1, p=0.016, respectively). Significant gene dose effects on the risk for substance abuse disorder and a major depressive episode were observed with the 861C allele (Armitage linearity tendency test: ²=7.20, df=1, p=0.008; ²=6.80, df=1, p=0.009, respectively). Substance abuse disorder and major depression appear to be associated with the h5-HTR_1B G861C locus in the patient population, but other psychopathologies such as bipolar disorder, schizophrenia, alcoholism, and suicide attempts were not found to be associated with this polymorphism. This preliminary result will need replication, given the limitations of association studies.