MRSI correlates of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder

BackgroundThe brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (1H MRSI).MethodFive unmedicated OCD patients (4 ♀, 13.5 ± 2.8) and 9 healthy controls (7 ♀, 13.0 ± 2.5) underwent MRSI (1.5 T, repetition-time/echo-time = 1500/30 ms) of bilateral putamen, thalamus and pregenual anterior cingulate cortex (pACC). Patients were rescanned after 12 weeks of exposure-based CBT. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) of OCD symptoms was administered before and after CBT.ResultsFour of 5 patients responded to CBT (mean 32.8% CY-BOCS reduction). Multiple metabolite effects emerged. Pre-CBT, N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) in left pregenual anterior cingulate cortex (pACC) was 55.5% higher in patients than controls. Post-CBT, tNAA (15.0%) and Cr (23.9%) in left pACC decreased and choline compounds (Cho) in right thalamus increased (10.6%) in all 5 patients. In left thalamus, lower pre-CBT tNAA, glutamate + glutamine (Glx), and myo-inositol (mI) predicted greater post-CBT drop in CY-BOCS (r = 0.98) and CY-BOCS decrease correlated with increased Cho.ConclusionsInterpretations are offered in terms of the Glutamatergic Hypothesis of Pediatric OCD. Similar to 18FDG-PET in adults, objectively measurable regional MRSI metabolites may indicate pediatric OCD and predict its response to CBT.

► CBT is an effective treatment for OCD, but its brain mechanism is unknown. ► We acquired MRSI of the brain in children with OCD before and after CBT. ► After CBT, metabolite levels changed in the cingulate and thalamus of OCD patients. ► Some metabolite changes correlated with symptomatic response to CBT. ► Results were interpreted using the Glutamatergic Hypothesis of Pediatric OCD.