title: Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes.
abstract: OBJECTIVE
  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.
  
  
  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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: • Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Toronto, ON, Canada.
authors.forename: Jennie G
authors.initials: JG
authors.lastname: Pouget
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Gonçalves
authors.forename: Erika L
authors.initials: EL
authors.lastname: Nurmi
authors.forename: Christopher
authors.initials: C
authors.lastname: P Laughlin
authors.forename: Karyn S
authors.initials: KS
authors.lastname: Mallya
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.forename: Michael G
authors.initials: MG
authors.lastname: Aman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McDougle
authors.forename: Lawrence
authors.initials: L
authors.lastname: Scahill
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Misener
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Brandl
authors.forename: Daniel
authors.initials: D
authors.lastname: Felsky
authors.forename: Amy Q
authors.initials: AQ
authors.lastname: Leung
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niedling
authors.forename: Werner
authors.initials: W
authors.lastname: Steimer
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
authors.forename: Jo
authors.initials: J
authors.lastname: Knight
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018079:Receptors, GABA / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome; D015430:Weight Gain / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: SLC25A4; TSPO; adenine nucleotide translocator; antipsychotic; genetics; mitochondria; peripheral benzodiazepine receptor; pharmacogenomics; schizophrenia; translocator protein-18 kDa; weight gain