OCD: Using Genome Data to Predict Risk, Symptoms and Treatment Response

The webinar, hosted by Dr. Jeff Borenstein, introduces Dr. Gwyneth Zai as the speaker for the session on Obsessive-Compulsive Disorder (OCD) genetics. Dr. Zai will discuss predicting risk, symptoms, and treatment response using genome data. The Brain and Behavior Research Foundation, under Dr. Borenstein's leadership, has funded innovative neuroscience and psychiatry projects since 1987, focusing on disorders like OCD. Dr. Zai's presentation will cover the complexity of OCD, genetic approaches to understand brain genes' role in OCD risk and antidepressant response, and identifying genetic variations linked to OCD risk.

Dr. Zai explains OCD, moving from its historical classification within anxiety disorders to its current status as a separate category. She describes the disorder's debilitating nature, affecting 1-3% of the population, characterized by obsessions and compulsions. The presentation highlights the importance of considering genetic factors in understanding OCD, referencing family and twin studies that suggest a hereditary component. The talk also touches on the biopsychosocial model, acknowledging the interplay of biological, psychological, social, and environmental factors in OCD's development.

This section delves into the specifics of genetic studies related to OCD, starting with candidate gene studies that examine individual genes for associations with OCD. It discusses the evolution of genetic research from single gene studies to genome-wide association studies (GWAS), which survey the entire genome. The summary also mentions the importance of looking at neurotransmitter systems like serotonergic, dopaminergic, and glutamatergic, which are implicated in OCD's biological mechanisms and treatment responses.

Dr. Zai presents findings from various GWAS on OCD, discussing the challenges of finding significant genetic markers due to the complex nature of the disorder. She mentions several studies, including one published in 2012 and a meta-analysis in 2018, which identified potential genetic associations within the glutamatergic system. The summary underscores the need for larger sample sizes to achieve genome-wide significance and the importance of international collaboration in genetic research.

The presentation examines the heterogeneity of OCD, aiming to categorize the disorder into more homogeneous subgroups based on genetic factors. Dr. Zai discusses clinical characteristics, such as gender differences, age of onset, symptom subtypes, and treatment responses, and how these may relate to specific genetic markers. The summary highlights the importance of understanding these genetic subtypes to improve diagnosis and personalized treatment approaches.

Dr. Zai explores the field of pharmacogenetics, focusing on how genetic variations can predict an individual's response to antidepressant medications, which are commonly used to treat OCD. The summary discusses the challenges of patients not responding to initial treatments and the potential benefits of genetic testing in guiding more effective, personalized medication choices. It also touches on the importance of considering both pharmacodynamic and pharmacokinetic factors in drug response.

This section summarizes the results of Dr. Zai's genetic studies on OCD, including candidate gene studies, genome-wide association studies, and pharmacogenetics. The summary highlights the complexity of OCD and the potential associations between specific genetic markers and symptom subtypes, treatment responses, and cognitive deficits. The discussion also looks ahead to future research directions, including the study of cognitive domains, cross-disorder approaches, and epigenetic biomarkers.

Dr. Zai emphasizes the importance of collaboration in advancing OCD research, acknowledging the contributions of mentors, colleagues, and various international groups. The summary stresses the collective effort required to make progress in understanding and treating OCD, from genetic studies to cognitive and epigenetic research, and the need for continued support and involvement from the scientific community.

The final part of the summary addresses the practical application of pharmacogenetics, with discussions on the current recommendations for genetic testing in relation to antidepressant treatment. It also explores the potential of future biomarkers, including epigenetic markers, imaging, and cognitive measures, to predict treatment response and the risk of developing OCD. The summary concludes with a Q&A session where Dr. Zai provides insights on comorbidity between OCD and other disorders, the potential use of TMS for OCD, and how individuals can get involved in research.