title: The role of the ITIH3 rs2535629 variant in antipsychotic response.
abstract: There is mounting evidence that schizophrenia risk variants influence response to antipsychotic medication. Common single nucleotide polymorphisms (SNPs) in or near the inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) gene have been repeatedly associated with schizophrenia and related psychiatric disorders in genome-wide association studies. Here, we provide the first study to assess the relevance of the ITIH3 rs2535629 SNP in response to antipsychotic medication.
  
  
  
  The rs2535629 SNP was genotyped in N=256 patients receiving various antipsychotics for up to 26weeks. Treatment response was assessed using the Brief Psychiatric Rating Scale (BPRS) including its positive and negative subscales. Follow-up analyses were performed after stratifying for ethnicity and medication.
  
  
  
  We found significant association of rs2535629 with improvement of negative symptoms in patients of European ancestry after six months of clozapine treatment (F1,87=8.8, pcorr=0.032). Patients homozygous for the minor A-allele showed the best improvement of negative BPRS scores. However, we observed no association between rs2535629 and changes in total BPRS score in the entire sample or the clozapine-treated subgroup.
  
  
  
  Although there was no association of genotype with overall changes in BPRS scores, the greater improvement of negative symptoms in minor allele carriers indicates that rs2535629 may help to identify a subset of schizophrenia patients with better treatment response to clozapine. Therefore, our findings provide the first suggestive evidence that rs2535629 is relevant in antipsychotic response.
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany; Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: E J
authors.initials: EJ
authors.lastname: Brandl
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: T A
authors.initials: TA
authors.lastname: Lett
authors.affiliation: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: N I
authors.initials: NI
authors.lastname: Chowdhury
authors.affiliation: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Bakanidze
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: H Y
authors.initials: HY
authors.lastname: Meltzer
authors.affiliation: Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine, CA, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Potkin
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York City, NY, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Lieberman
authors.affiliation: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: daniel.mueller@camh.ca.
authors.forename: D J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000328:Adult; D000510:Alpha-Globulins / Q000235:genetics*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D010054:Brief Psychiatric Rating Scale; D003024:Clozapine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
chemical_list: D000510:Alpha-Globulins; D014150:Antipsychotic Agents; C011877:inter-alpha-inhibitor; D003024:Clozapine
keywords: Clozapine; ITIH3; Schizophrenia; Treatment response; rs2535629