Investigation of the relationship of treatment resistance with autistic traits and obsessive-compulsive symptoms in schizophrenia through related genetic polymorphisms

Objective: The aim of this thesis is to investigate the relationship between obsessive-compulsive symptoms (OCS), which may be associated with treatment resistance in schizophrenia patients, and autism spectrum disorder (ASD) characteristics and the role of some polymorphisms of BDNF, COMT, HTR2A and SLC6A4 genes, which have previously been found to create susceptibility to OCS in schizophrenia patients. Materials and Methods: A total of 136 participants, including 70 patients with treatment-resistant schizophrenia and 66 patients with schizophrenia without treatment resistance, were included in the study. In the first stage, all participants were administered the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Schizophrenia Scale (CGI-SS) to assess schizophrenia symptoms, the Insight Rating Scale (IRS) to assess their awareness of their symptoms, and the Calgary Depression Scale in Schizophrenia (CDSS) to assess depression severity. The Yale-Brown Obsession-Compulsion Scale (YB-OCS) was then administered to assess the severity of OCD; the PANSS Autism Severity Scale (PAUSS), Repetitive Behaviors Scale-Revised-Turkish Version (TEDÖ-R-TV), Adult Autism Spectrum Questionnaire (OSA), Mind Reading Through Eyes Test (GZOT) and Diagnostic Autism Spectrum Interview (DASI) were administered to assess autistic features. Raven Standard Progressive Matrices Test (RSPMT) was administered to all patients to assess premorbid cognitive functions. In the second stage, blood samples were taken from the patients in the treatment-resistant schizophrenia group and polymorphisms of BDNF, COMT, SLC6A4 and HTR2A genes were investigated and their association with OCD was evaluated. Results: No significant difference was found between the two groups in terms of sociodemographic characteristics and schizophrenia symptom severity. In treatment-resistant schizophrenia patients, OCS severity and autistic characteristics were found to be significantly higher compared to patients who were not resistant to treatment. In the treatment-resistant schizophrenia group, OSA, TEDO total and PAUSS scores of patients with high OCD severity were found to be significantly higher. As a result of multiple linear regression analysis, only OSA scores predicted OCS in this group. In addition, although the frequencies of polymorphisms belonging to BDNF, COMT, HTR2A and SLC6A4 genes differed in the treatment-resistant schizophrenia group compared to the healthy population, no significant association was found with OSA. Conclusion: OCD and autistic features seem to be associated with treatment resistance in schizophrenia. Therefore, it is important to address the diagnosis and differential diagnosis of autism spectrum disorder and OCD in treatment-resistant schizophrenia patients. It is recommended to investigate polymorphisms including glutamatergic genes in larger samples in order to determine the role of polymorphisms of OCD and ASD related genes in this patient group.