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Obsessive-Compulsive Disorder (OCD) is a severe psychiatric disorder, which is characterized by the presence of repetitive thoughts, urges or images with a frightening or disgusting content (obsessions) and mental or behavioral acts that are performed over and over again (compulsions). In OCD chronicity is the rule rather than the exception, quality of life is extremely low and family burden is high. Treatment is available, but its effectiveness is limited. Today Cognitive Behavior Therapy (CBT)outperforms other treatments, however, only a part of the patients receives adequate CBT, because many refuse it or drop-out, both most probably because CBT provokes high levels of anxiety. New less anxiety provoking treatments, with other working mechanisms than CBT could enhance treatability of OCD. A psychological treatment that probably meets both criteria, i.e., 1) other mechanism of action, 2) less anxiety-provoking, and that has been proven to be effective for OCD in previous studies, is the Inference Based Approach (IBA). IBA teaches patients how to stay in touch with reality by actively relying on sensory information of the very moment.



The goals of the present study are to reduce chronicity in OCD, by comparing the effectiveness of the Inference Based Approach (IBA) with that of Cognitive Behavior Therapy (CBT) and by identifying biomarkers, socio demographic and clinical factors that predict a better treatment outcome to one compared to the other treatment modality, also establishing the mechanisms of action in both interventions. The ultimate goal is to use the most effective modality for the individual patient, by linking disease profile and stage specific brain substrate and the mechanism of action of the treatment modality.



To study the effectiveness of IBA compared to CBT a multisite randomized controlled non-inferiority trial will be performed in a sample of patients with OCD. Participants will be randomized to 20 sessions IBA vs 20 sessions CBT after baseline measurements.

To study the predictive value of pre-treatment network connectivity to treatment outcome, and to study explanatory mechanisms of change across treatment modalities, in a subsample of patients structural and functional MRI will be collected pre- and post treatment.



*IBA is non-inferior to CBT in treating patients with OCD.

*IBA is superior to CBT in treating patients with OCD with poor insight.

*Pre-treatment decreased activation in the ventromedial prefrontal cortex (vmPFC) / subgenual anterior cingulate cortex (sgACC) and increased sgACC-amygdala connectivity predicts good response to CBT. In contrast, we predict that decreased activation in the dorsolateral prefrontal cortex (dlPFC) and dorsal ACC (dACC) predicts good response to IBA. We expect that CBT will normalize vmPFC-amygdala connectivity (relevant for extinction learning), whereas IBA will normalize the connectivity between the dorsal prefrontal regions (dlPFC/dACC) and striatum (relevant for selective attention and cognitive inhibition).



Referred patients (aged 18 years and older) with a primary DSM-5 diagnosis OCD.



In a single session of 60 minutes prior to treatment and another session directly after treatment completion we will study network connectivity 1) during rest, 2) during selective attention, and 3) during symptom provocation. We will combine functional connectivity measures with structural brain measures, both grey matter volume and white matter integrity.



The proposed study fits well in the research program GGZ-Middellange projecten, because it aims to prevent unnecessary chronicity in patients with OCD by the means of studying the effectiveness of a new promising treatment, by identifying biomarkers that predict treatment response and identifying explanatory working mechanisms of treatment.

Patients state that the proposed study meets their needs because it studies a new psychotherapy. They welcome every new treatment possibility, because it might bring new opportunities for recovery. Also relevant for GGZ-Middellange projecten is that patients participate in the project and that e-health is part of the project.

The proposed study gerenates much knowlegde which will easily find its way to clinical practise. As a product of the study, the new intervention is available. As is an e-health package consiting of psycho-education and homework assignments for both of the interventions. Another product concerns the neuroimaging-based predictors of treatment response (separate for both treatment conditions). The predictors of treatment response will be used in collaboration with other institutes within an international OCD network, to test reproducibility and reliability in unrelated OCD samples.

Management of data will be conform FAIR-data principles.



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