The role of the ITIH3 rs2535629 variant in antipsychotic response.

INTRODUCTION: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. METHODS: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. RESULTS: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. DISCUSSION: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.

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