A View Through the Neural Panes: A Multimodal Journey into OCD: Structural, Neurometabolic, and Functional Insights

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition characterized by recurrent and unwanted obsessions and compulsions. Obsessions are persistent, unwanted thoughts or impulses that cause anxiety. Compulsions are repetitive behaviors performed to reduce the experienced anxiety. OCD has four distinct symptom dimensions: 1) fear of contamination and cleaning compulsions, 2) symmetry, ordering, and counting, 3) aggressive, sexual, and blasphemous obsessions, and 4) hoarding and checking. OCD often co-occurs with other disorders, such as depression and anxiety. Treatment options include psychotherapy and pharmacotherapy, with cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) being the most effective psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) are the first choice for medication. However, these treatment strategies are not equally effective for everyone. A better understanding of the underlying neurobiological processes of OCD may help improve treatment. Although much imaging research has been conducted on the structure and function of the brains of people with OCD, significant questions remain unanswered due to the limitations of previous studies, including the confounding effects of medication use and small sample sizes. Additionally, relatively little research has been done on changes in neurotransmitters in the brains of people with OCD. There is suspicion that important neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA), differ in the brains of individuals with OCD. One reason for the limited research on neurotransmitters is the technical limitations of current measurement methods. Therefore, two important approaches are needed to better understand the underlying neurobiology of OCD. First, large-scale, harmonized research with large participant groups and detailed clinical characterization is required. Second, there is a need for technically advanced studies that investigate potential differences in neurotransmitters between individuals with and without OCD. The goal of the studies in this dissertation was therefore twofold. The first aim was to reliably identify structural brain differences between medication-free OCD patients and healthy controls by using larger sample sizes. By also collecting detailed clinical information from this large group of participants, we aimed to better understand the relationships between these findings and clinical variables such as disease duration, comorbid anxiety, and depression. These analyses are based on data collected in the Global OCD study, a worldwide consortium where data collection and processing were harmonized. The second aim was to better understand whether there are consistent differences in neurotransmitter concentrations between individuals with and without OCD, and how these neurotransmitters relate to clinical features or change after undergoing psychotherapy. We also sought to map how neurotransmitters change during exposure to OCD-related images in an MRI scanner by using technologically innovative imaging techniques. This dissertation includes five studies that utilize various imaging techniques to gain a deeper insight into the neurobiological mechanisms of OCD and potentially contribute to the development of more effective treatments in the future.