The International Journal of Neuropsychopharmacology

Review Article

Association of the HTR2C gene and antipsychotic induced weight gain: a meta-analysis

Vincenzo De Lucaa1a2 c1, Daniel J. Muellera1, Andrea de Bartolomeisa2 and James L. Kennedya1

a1 University of Toronto, Centre for Addiction and Mental Health, Neurogenetics Section, Toronto, ON, Canada

a2 University ‘Federico II’, Section of Psychiatry, Department of Neurosciences, Naples, Italy


The 5-HT2C receptor has been hypothesized to represent an important modulator in feeding behaviour. Evidence was based on the observation that knock-out mice for the 5-HT2C receptor gene (HTR2C) develop obesity and that many atypical antipsychotics with potent 5-HT2C antagonism may induce weight gain in susceptible individuals. Pharmacogenetic studies focusing mainly on the –759C/T promoter polymorphism (rs3813929) of the X-linked HTR2C gene revealed controversial results. We investigated the association of the HTR2C gene and weight gain using meta-analytical techniques, combining all published data while restricting our analysis to studies investigating the 759C/T. We also investigated whether ancestry (Caucasian vs. Asian) and clinical factors moderated any association. We found evidence for a slight association of –759C/T with weight gain and significance between studies for heterogeneity. Our meta-analysis provides support for the association of HTR2C in weight gain but indicates that firmly establishing the role of pharmacogenetics in clinical psychiatry requires much larger sample sizes that have been hitherto reported.

(Received September 17 2006)

(Reviewed November 16 2006)

(Revised November 22 2006)

(Accepted December 18 2006)

(Online publication February 12 2007)


c1 Address for correspondence: V. De Luca, M.D., Neurogenetics Section, CAMH, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. Tel.: (+001) 416.5358501 (ext. 4421) Fax: (+001) 416.979.4666 E-mail: