M94 - THE GENOMICS OF HIGHLY TREATMENT RESISTANT SCHIZOPHRENIA
Abstract
Understanding the molecular basis of Schizophrenia (SCZ) is one of the most significant problems in psychiatry. The minimal identification of single genes greatly limits the actionability of genomic findings - we need single gene targets for clinical utility, etiological investigation, and therapeutic development. Modern SCZ association studies analyze ~105 subjects to achieve statistical power. To achieve these sample sizes, a range of SCZ subjects – from mild to severe – are included. A time-honored and complementary strategy in genetics is to study an extreme phenotype– here, highly-treatment resistant SCZ (HTRS). It is known that rare Mendelian disorders (e.g., Wilson's Disease) can be misdiagnosed as SCZ because they initially present with psychosis in some individuals. In some of these misdiagnosed cases, antipsychotics are not effective. Therefore, genetically screening individuals with HTRS may uncover Mendelian disorders that present as psychosis and are misdiagnosed as SCZ. If ideal HTRS subjects can be identified, we can screen their genomes for rare Mendelian disorders that mimic SCZ.