Using common variant analyses (GWAS) for defining an inflammatory subtype of schizophrenia to genetically inform adjuvant anti - inflammatory treatment

Genome-wide association studies (GWAS) have been enormously successful in psychiatric research.1 Here we will present further advances towards our understanding of schizophrenia, through the use of optimized methodology... [ view full abstract ]

Genome-wide association studies (GWAS) have been enormously successful in psychiatric research.¹ Here we will present further advances towards our understanding of schizophrenia, through the use of optimized methodology implemented in Berlin, Germany. In a first phase we are aiming to collect 2,500 individuals with schizophrenia and 2,500 healthy controls within two years with an optimized collection strategy.

Repurposed drugs for the treatment of psychiatric illness have a long history; indeed, the initial first-generation antipsychotic – chlorpromazine – was originally developed to support anesthesia. Based on the proinflammatory hypothesis of schizophrenia, several small randomized placebo-controlled studies on adjuvant use of nonsteroidal anti-inflammatory drugs (NSAIDs) for schizophrenia were performed, a recent meta-analysis revealed that NSAIDs may have benefits for positive symptoms.²    

With the method of specific polygenic risk scoring we will genetically define an inflammatory schizophrenia subgroup. We will reinvite 50 schizophrenia patients with extremely high and extremely low inflammatory risk scores and perform an adjuvant double blind treatment trial with repurposed aspirin.

Here we will present the methodology for this study, involving specific polygenic risk scores. 

¹ Ripke, S. et al. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).    

² Nitta, M. et al. Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials. Schizophr. Bull. 39, 1230–1241 (2013).