The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain

Trehani M. Fonseka, Arun K. Tiwari, Vanessa F. Gonc¸alves, Jefrey A. Lieberman, Herbert Y. Meltzer, Benjamin I. Goldstein, James L. Kennedy, Sidney H. Kennedy, Daniel J. Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Objectives. Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG). Methods. Nineteen polymorphisms were genotyped using Taqman® assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. Results. In European patients, IL-1β rs16944∗GA (P = 0.013, Pcorrected = 0.182), IL-1β rs1143634∗G (P = 0.001, Pcorrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127∗A (P = 0.049, Pcorrected = 0.784), and IL-1β rs16944∗GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+TT, PPerm = 0.029), and IL-6 rs2069837 (Val/Val+AA, PPerm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+GA, PPerm = 0.006) in African Americans. Conclusions. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalWorld Journal of Biological Psychiatry
Issue number1
StatePublished - Jan 1 2015


  • Antipsychotic-induced weight gain
  • Cytokine
  • Genetics
  • IL-1β, BDNF

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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