Advances in Psychiatry

Obsessive compulsive disorder (OCD), characterized by intrusive and repetitive thoughts and behaviors, often begins in childhood and continues throughout one’s life. Cognitive-behavioral therapy (CBT) with exposure and response prevention (ERP), a first-line treatment for OCD, has been shown to be effective for many individuals, but not all.

Dr. Kate Fitzgerald

“Treating OCD at younger ages can prevent a lifetime of distress, but better and more targeted treatments are needed,” says Kate D. Fitzgerald, MD, the Ruane Professor of Child and Adolescent Psychiatry at Columbia University and a psychiatrist with the New York State Psychiatric Institute and NewYork-Presbyterian/Columbia. “Nearly 50 percent of people with OCD continue with clinically significant illness after receiving exposure and response prevention (ERP) treatment. As clinicians, we are unable to predict who will benefit and who will not [from ERP].”

ERP is associated with symptom improvement, but there is great variability in treatment responses across patients with some work suggesting more robust response at younger ages. Dr. Fitzgerald’s research focuses on elucidating developmentally sensitive mechanisms of cognitive behavioral therapy for patients at various ages.

Cortical-subcortical circuits related to affective-behavioral integration and cognitive control develop through childhood and adolescence and are implicated in OCD. Dr. Fitzgerald sought to examine whether connectivity in cortical-subcortical circuits predict treatment response to ERP in teens and adults with OCD, and whether connectivity predictors differ in younger compared to older patients.

Rendering of the human brain

Using resting-state functional MRI (fMRI) imaging, Dr. Fitzgerald and her research colleagues measured brain connectivity patterns in 116 participants (54 adolescents and 62 adults) randomly assigned to 12 weeks of either ERP or a control therapy involving stress reduction and problem-solving, stress management therapy (SMT). Prior to treatment, resting-state connectivity of cortical (ventromedial prefrontal, cingulo-opercular, frontoparietal) and subcortical regions were assessed with fMRI. The researchers evaluated OCD severity with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before, during, and after treatment.

“This is the first study to our knowledge to examine resting-state functional connectivity predictors of response to ERP compared with an active control psychotherapy, and the first study to directly compare neural predictors of treatment response in adolescents and adults.” – Dr. Kate Fitzgerald and study co-authors

The results of the study, which were published in the December 7, 2022 issue of the American Journal of Psychiatry, demonstrated that across all age groups, both ERP and SMT reduced OCD symptoms, although ERP proved to have more pronounced and clinically significant effects. Additionally, they found that:

• ERP response was selectively associated with less ventromedial prefrontal -subcortical connectivity in both age groups
• Adolescents and adults who had the most active pre-treatment connections in cortical-subcortical circuits involved in cognitive control responded better to either ERP or SMT treatment
• Stronger connectivity between the ventral striatal region of the brain linked to reward processing with frontoparietal areas of the cortex linked to cognitive control characterized better treatment response in adolescents compared to adults
• Greater connectivity between these frontoparietal regions also predicted greater decreases in symptom scores across conditions, but only in adults
• Y-BOCS decreased significantly among those who received ERP versus SMT

“Across age groups, we found that vmPFC-striatothalmic circuitry was uniquely associated with symptom improvement with ERP, while connectivity of cognitive control regions was associated with symptom improvement irrespective of treatment type,” the authors wrote. “Additionally, ventral striatal connectivity distinguished treatment response in adolescents compared with adults. Our findings help delineate the neural circuitry that supports response to psychotherapy based on treatment modality and suggest that developmental differences are an important factor to consider when examining the neural mechanisms of psychotherapy.”

Dr. Fitzgerald notes that understanding neural differences could help guide the development of novel treatments. Her lab is now working on both developing new treatments for children with OCD and increasing the effectiveness of existing therapies.

“One direction that we will take is to use cognitive training to shift the balance of connectivity in brain circuits for cognitive control in OCD-affected youth,” says Dr. Fitzgerald. “The brain is still developing through childhood and adolescence, and it is possible that boosting function in circuits for cognitive control could help children with OCD respond to ERP.”