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Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes
Jennie G Pouget1, Vanessa F Gonçalves, Erika L Nurmi
1• Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Toronto, ON, Canada.
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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