Pharmacogenetic dissection of central and peripheral candidate genes in atypical antipsychotic-induced weight-gain

Vincenzo S. Basile*, Mario Masellis, Vincenzo DeLuca, Herbert Y. Meltzer, Jeffrey A. Lieberman, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

A drawback to the treatment of schizophrenia with atypical antispsychotics (AAs) is the occurrence of weight gain. Variability exists among individuals regarding this weight gain and genetic predisposition has been suggested. AAs may potentially disrupt both central mechanisms regulating appetite and peripheral mechanisms governing energy expenditure to cause weight gain. Evidence supports a role for the serotonin 2C and histamine H1 receptors in central hypothalamic regulation of food intake and consequently for AA induced weight gain. There is also support for peripheral AA disruption of thermogenesis and metabolic rate via TNFα, β3 and α1 adrenergic receptors. We investigated these candidate genes in 77 patients with DSM-IIIR diagnoses of schizophrenia that were prospectively assessed for clozapine-induced weight gain. ANCOVA analyses correcting for covariates were utilized to detect differences among genotypes. Although results were predominantly negative, trends were noted for TNFα (F[2,72] = 2.58, P = 0.12; means per genotype of 7.4 ± 3.7, 2.3 ± 4.1 and 3.9 ± 4.5) and the α1 adrenergic receptor (F[2,57] = 1.45, P = 0.24; Arg/Arg = 3.24 ± 3.1; Arg/Cys = 4.89 ± 4.9; Cys/Cys = 0.85 ± 3.4). These candidate genes may be involved in clozapine induced weight gain, although replication is necessary.

Original languageEnglish (US)
Pages (from-to)581-582
Number of pages2
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume105
Issue number7
StatePublished - Oct 8 2001

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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