EXPLORING IMMUNOLOGICAL AND MOLECULAR MECHANISMS INVOLVED IN OBSESSIVE-COMPULSIVE DISORDER WITH COMORBID NEURODEVELOPMENTAL DISORDERS

Abstract Background Obsessive-compulsive disorder(OCD) is a debilitating condition that has a lifetime prevalence of 1%–2% and an average age of onset of approximately 20 years. Although various treatments, such as antidepressants, have been widely used, the pathogenesis of the disease remains unclear. In addition, the onset and severity of OCD are associated with comorbidity of various neurodevelopmental disorders(NDD), such as autism spectrum disorder, attention deficit/hyperactivity disorder, and Tourette’ s or tic disorder. In recent years, immunological mechanisms of OCD such as Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus have been proposed. In Europe and the United States, a number of meta-analyses have investigated the immunological mechanism of OCD especially the associations between OCD and serum cytokine levels. However, most of these studies have focused on the comparisons between OCD patients and healthy controls, and there are no studies regarding the immunological or molecular mechanisms of OCD, especially its causal relation with comorbidities of NDD. Aims & Objectives We aimed to elucidate the developmental mechanism of OCD by examining the involvement of immune factors in OCD and its comorbidities and by determining immune-related genes that are differentially expressed in OCD patients with and without comorbidity of NDD. Method Whole blood samples were collected at the Department of Neuropsychiatry, Hyogo Medical University Hospital from inpatients and outpatients who met the Diagnostic and Statistical Manual-5(DSM-5) criteria for OCD. RNA was extracted from the blood samples and subjected to whole exome sequencing. Genes with a false discovery rate<0.3 were designated as differentially expressed using edgeR software. Molecular analyses were conducted using an established pipeline and Ingenuity Pathway Analysis (IPA) software. We also measured the levels of IL1β, IL6, IL18, TNFα, and other cytokines. Clinical symptoms were assessed by a trained psychiatrist using various rating scales. The presence of comorbid NDD was also determined using the structured diagnostic interview according to DSM-5. Written informed consent was obtained from all participants and the study was approved by the Ethical Review Committee of Hyogo Medical University Hospital(Approval number: 3960). Results At this time, 8 OCD patients with and without any comorbidity of NDD were differentiated and analyzed. IPA showed involvement of several biological pathways relevant to immunological function. Other functions, such as neural functions, were also indicated. Discussion & Conclusion Our results indicate a potential role of inflammation in OCD patients with any comorbidity of NDD. Moreover, other candidate molecules that affect severity were also suggested. However, caution should be exercised in interpreting the results because of the small sample sizes, and further studies in a lager sample are required to validate our results.