Exploring immunological and molecular mechanisms involved in obsessive-compulsive disorder with comorbid...

Obsessive-compulsive disorder (OCD) is a psychiatric disease with a prevalence of 2%-3%. Despite the effectiveness of antidepressants, such as serotonin reuptake inhibitors, for treating OCD, its pathogenesis remains unclear. Recent research has implicated immunological mechanisms, particularly in OCD patients with comorbid neurodevelopmental disorders (NDD), such as autism spectrum disorder, attention deficit/hyperactive disorder, and Tourette's disorder. To examine these mechanisms, we investigated immunological factors involved in OCD patients with any NDD comorbidity (OCD + NDD group), compared with those without comorbid NDD (OCD group).

Twenty-eight OCD patients treated at Hyogo Medical University Hospital were recruited for this study. Of them, 14 patients with NDD comorbidity (OCD + NDD) were compared with 14 patients without comorbid NDD (OCD). RNA was extracted from blood samples and analyzed using RNA sequencing and Ingenuity Pathway Analysis (IPA). Plasma levels of IL11 and IL17A were measured with ELISA.

RNA sequencing identified 716 significantly differentially expressed genes, with 47 related to immune functions, in the OCD + NDD group compared with the OCD group. IL11 and IL17A were central, with IL11 linked to neutrophil production and IL17A to T cell migration and cytokine secretion. Pathway analysis indicated complex interactions among these genes.

This study highlights significant immunological changes in OCD patients with any NDD. Decreased anti-inflammatory IL11 and increased proinflammatory IL17A suggest a shift towards inflammation, which may contribute to neurodevelopmental issues.

Immunological dysregulation in OCD with comorbid NDD may offer potential therapeutic targets. Immune gene interactions should be further investigated in effort to improve treatment strategies for treatment-refractory OCD patients, especially those with neurodevelopmental comorbidities.