AN EXAMINATION OF THE GUT MICROBIOME IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER VERSUS HEALTHY CONTROLS

Abstract

Obsessive-Compulsive Disorder (OCD) is a debilitating, chronic neuropsychiatric disorder estimated to effect approximately 1-2% of the Canadian population. Our understanding of the pathophysiological mechanisms involved in OCD is unclear, as evidenced by the moderate response associated with treatments targeting these putative pathways. As such, there is a need to explore novel mechanisms of disease. Recent research has focused on the gut-brain axis and highlighted the potential role of the gut microbiota in psychiatric conditions. Further, the role of inflammation is also gaining traction in psychiatric research. This thesis investigates the role of these commensal gut bacteria in OCD, by examining stool samples of unmedicated, non-depressed OCD outpatients and healthy community controls. Given that systemic inflammation is a suggested pathway by which gut bacteria effect behaviour, morning levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor-necrosis factors-α (TNF-α) were also examined. To our knowledge, this thesis is the first investigation of the gut microbiome in OCD. This thesis describes: (1) a critical review of the literature developing a theoretical basis for a role of microbial dysbiosis in OCD; that (2) three specific genera and species richness/diversity are lower in OCD patients compared to controls; (3) mean CRP, but not IL-6 and TNF-α, is elevated in this sample of OCD patients; and (4) gastrointestinal symptom severity and prevalence of irritable bowel syndrome is higher in OCD. Taken together, this thesis is the first study to provide evidence for microbial dysbiosis in OCD. Although systemic inflammation may not mediate the relationship between reduced diversity and OCD symptomatology, these results provide evidence for mild systemic inflammation. Further gastrointestinal and psychiatric symptom severity are positively correlated, but not specific to patients with IBS. These results suggest the gut microbiome may be a potential pathway of interest for future OCD research, clinical implications are also made.