Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

Pouget, Jennie G. and Gonçalves, Vanessa F. and Nurmi, Erika L. and Laughlin, Christopher P. and Mallya, Karyn S. and McCracken, James T. and Aman, Michael G. and McDougle, Christopher J. and Scahill, Lawrence and Misener, Virginia L. and Tiwari, Arun K. and Zai, Clement C. and Brandl, Eva J. and Felsky, Daniel and Leung, Amy Q. and Lieberman, Jeffrey A. and Meltzer, Herbert Y. and Potkin, Steven G. and Niedling, Charlotte and Steimer, Werner and Leucht, Stefan and Knight, Jo and Müller, Daniel J. and Kennedy, James L. (2015) Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes. Pharmacogenomics, 16 (1). pp. 5-22. ISSN 1462-2416

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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.

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08 Jun 2016 08:28
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20 Sep 2023 00:53