Family and case-control association study of the tumor necrosis factor-alpha (TNF-α) gene with schizophrenia and response to antipsychotic medication

Gwyneth Zai, Daniel J. Müller, Jan Volavka, Pal Czobor, Jeffrey A. Lieberman, Herbert Y. Meltzer, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Background: Dysregulation of the immune system has been suggested to play a role in the etiology of schizophrenia (SCZ). In this context, the tumor necrosis factor-alpha (TNF-α) is considered an interesting candidate for genetic studies as overproduction of TNF-α, which may be genetically modulated, can influence neuron growth and proliferation. Moreover, the TNF-α gene is located on chromosome 6p21.3, a region that has been found to be associated with SCZ in numerous linkage studies. One functional polymorphism, G-308A, has been studied for association with SCZ yielding inconsistent findings. Results and discussions: In our study, we investigated the G-308A polymorphism with SCZ including 95 nuclear families and 149 pairs of cases/controls matched by age, gender, and ethnicity. Furthermore, we examined BPRS change scores (after 6 weeks, 3 months, and 6 months) and weight changes (after 6 weeks) with this polymorphism in 153 and 247 patients, respectively, after clozapine treatment. We did not observe biased transmission using family-based association test (P=0.752) or significant differences in case/control studies (P=0.839). However, patients with allele A showed significant improvement on BPRS change score after 3 months (t=2.000, P=0.049) and 6 months (t=2.481, P=0.015) of clozapine treatment when compared with patients without allele A. Moreover, trends were observed for genotype A/A with clinical improvement in BPRS change score after 6 months (F=2.834, P=0.065) using ANCOVA, and for allele G with weight gain (t=-1.702, P=0.091). Conclusion: Overall, the G-308A polymorphism of the TNF-α gene does not appear to play a major role in SCZ but might be involved in antipsychotic response.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalPsychopharmacology
Volume188
Issue number2
DOIs
StatePublished - Oct 2006

Funding

Acknowledgements This work has been supported by the Ontario Graduate Scholarship (GZ), the Institute of Medical Science Continuing Award (GZ), and the Canadian Institutes of Health Research (CIHR) postdoctoral fellowship award (DJM). Gwyneth Zai and Daniel J. Müller have contributed equally to this work.

Keywords

  • Clozapine response
  • Clozapine-induced weight gain
  • Family-based association test (FBAT)
  • Schizophrenia
  • Transmission disequilibrium
  • Tumor necrosis factor-alpha (TNF-α)

ASJC Scopus subject areas

  • Pharmacology

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