Neuromelanin-Sensitive MRI as a Marker of Dopamine Hyperactivity and CBT Response in Children With Obsessive-Compulsive Disorder

ABSTRACT

Background: Positron Emission Tomography (PET) findings suggest that increased striatal dopamine neurotransmission may underlie Obsessive-Compulsive Disorder (OCD) in adults. This is untested in pediatric OCD since PET is overly invasive and untenable for pediatric research. Thus, we used neuromelanin-sensitive MRI (NM-MRI) to assess nigrostriatal dopamine transmission in children with OCD and predict response to cognitive behavioral therapy (CBT). Methods: NM-MRI data was collected from 35 children on a GE 3T scanner with a 64-channel head coil. Those with OCD received manualized CBT before being re-scanned after 16-10 weeks. Following stringent QC procedures, 10 scans were excluded, leaving baseline and follow-up data from 15 children with OCD (9.7±1.7 years) and 10 matched controls (10.0 ± 1.8 years). Data were preprocessed with in house procedures (Wengler et al, Neuroimage, 2020). Linear regression analyses assessed group differences in dopamine signal and associations with CBT response. Results: Group differences in NM-MRI signal were detected in the VTA with greater signal in the OCD compared to HC group (t(14.45)=-2.13, p=.05). NM-MRI signal did not correlate significantly with baseline OC symptoms, but predicted better CBT response in the OCD group (p=.04), as measured by change in symptoms pre-post CBT. Conclusions: These new findings suggest alterations in the mesocortical dopaminergic system in pediatric OCD, stemming from the VTA. Dopaminergic hyperactivity may contribute to the reward processing deficits noted in OCD and mark CBT response in pediatric patients. Data collection has resumed (post COVID-19) and we anticipate increasing the sample size before the SOBP meeting in April. Supported By NIMH R01MH115024-01A1 Keywords Pediatric Obsessive-Compulsive Disorder, Neuromelanin-Sensitive MRI, Precision Psychiatry, Dopamine, Cognitive Behavioral Therapy