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Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published
  • Jennie G. Pouget
  • Vanessa F. Gonçalves
  • Erika L. Nurmi
  • Christopher P. Laughlin
  • Karyn S. Mallya
  • James T. McCracken
  • Michael G. Aman
  • Christopher J. McDougle
  • Lawrence Scahill
  • Virginia L. Misener
  • Arun K. Tiwari
  • Clement C. Zai
  • Eva J. Brandl
  • Daniel Felsky
  • Amy Q. Leung
  • Jeffrey A. Lieberman
  • Herbert Y. Meltzer
  • Steven G. Potkin
  • Charlotte Niedling
  • Werner Steimer
  • Stefan Leucht
  • Daniel J. Müller
  • James L. Kennedy
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<mark>Journal publication date</mark>01/2015
<mark>Journal</mark>Pharmacogenomics
Issue number1
Volume16
Number of pages18
Pages (from-to)5-22
Publication StatusPublished
<mark>Original language</mark>English

Abstract

AIM: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain.

PATIENTS & METHODS: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119).

RESULTS: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10(-3)), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10(-3)) and RUPP samples (p = 2.76 × 10(-4)).

CONCLUSION: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect.