Targeting compulsivity Treatment mechanisms in obsessive-compulsive disorder

The main aim of this thesis was to investigate the neural mechanisms underlying the treatment of OCD. First-line treatment for OCD consists of pharmacological treatment with SSRIs and/or psychological treatment with CBT. Both treatments have proven to be effective, but the neural mechanisms underlying successful treatment remain unclear. In this thesis, comprehensive research is presented on both the long and short term effects of treatment, analyzing data from a pediatric and adult OCD sample and comparing both treatment modalities (SSRIs vs. CBT). Additionally, we tested whether the current neurobiological model of OCD is still accurate and supports the current treatment protocols. Our findings implicate that distress-induced compulsivity is predominantly associated with involvement of the goal-directed network. This shines new light on the pathophysiology of OCD and further substantiates the current treatment of choice, i.e., cognitive behavioral therapy. Furthermore, we showed that treatment induced neural changes in children are long-lasting during a period of ongoing brain maturation. We then provided first insight in the common and specific neural mechanisms underlying treatment response, suggesting that CBT and SSRIs support recovery from OCD along partly distinct pathways. Furthermore, we showed that treatment induced changes are not only limited to the CSTC circuits, but are widespread across different areas of the brain. Finally, we propose the addition of the insula to the neurobiological model of the disorder as an import neural mediator in treating OCD, possibly leading towards the enhancement of current treatments and the development of novel treatment options.