This is a competitive renewal application of the Principal Investigator's grant award RO1MH59299. Obsessive compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling disorder that emerges during childhood or adolescence in as many as 80% of all cases. The clinical phenomenology/nosology and empirical treatment for pediatric OCD have been well delineated making pediatric OCD a leading candidate for developmental neurobiologic study. OCD is also less vulnerable to ambiguities in expression across the lifetime and permits us to study the disorder close to illness onset while remaining applicable to adult subjects. The overall goal of this project, which combines treatment and magnetic resonance imaging expertise at Wayne State University, is to further explicate the underlying neurobiology of pediatric OCD. The effectiveness of treatment with either a selective serotonin reuptake inhibitor (SSRI) or cognitive behavioral therapy (CBT) for pediatric OCD has been demonstrated. Exciting new pilot data under NIMH grant mechanisms (R01MH59299, K24MH02037) suggest that both the SSRI, paroxetine, and CBT return neurobiological functioning toward normal in pediatric OCD patients who improve symptomatically, but perhaps through different mechanisms. This convergence of findings from neurodiagnostic and treatment research presents a unique opportunity to deepen our understanding of the etiopathogenesis of pediatric OCD in the context of the clinically relevant question, """"""""Which treatments for which child with which set of subgrouping characteristics (e.g., SSRI or CBT for patients with increased choline and decreased N-acetyl-aspartate)?"""""""" Recent developments in neuroimaging allow for the direct and noninvasive monitoring of brain neurochemistry in multiple brain regions via proton magnetic resonance spectroscopic imaging (1H MRSI). Compounds that can be measured include the putative neuronal marker, N-acetyl-aspartate (NAA), and choline (Cho). Preliminary studies suggest localized functional neurochemical marker alterations in ventral prefrontal-striatal-thalamic circuitry. No alterations were observed in regions not implicated in the pathogenesis of OCD, e.g., dorsolateral prefrontal cortex, parietal white matter and occipital cortex. Using targeted 1H MRSI to define the primary dependent variables, we propose to employ a 2 (treatment) x 5 (repeated assessments) experimental design to further explicate the neurochemistry of childhood OCD before and during 12 weeks of acute treatment with either paroxetine or CBT and after 6 months of naturalistic follow-up treatment. An untreated normal control group is included to characterize selected MRI markers with regard to normalization with treatment. This combination of biological and behavioral/symptomatic predictor and outcome variables enacts the call for translation approaches to mental illness and may potentially lead to a better mechanistic understanding of pediatric OCD and, in turn, to new diagnostic and treatment approaches.
Showing the most recent 10 out of 51 publications
