RESUMEN
OBJECTIVE: Foundational knowledge on neural circuitry underlying pediatric obsessive-compulsive disorder (OCD) and how it changes during standard treatment is needed to provide the basis for conceptualization and development of novel targeted treatments. This study explored the effects of sertraline, a selective serotonin reuptake inhibitor, on resting-state functional connectivity in cortico-striatal-thalamic-cortical circuits in pediatric OCD. METHOD: Medication-free youths with OCD (n = 14) and healthy controls (n = 14) were examined at baseline and 12 weeks with resting-state functional magnetic resonance imaging. Between scan sessions, participants with OCD received 12 weeks of sertraline. For each scan, seed-based whole-brain resting-state functional connectivity analyses were conducted with 6 striatal seeds. Analysis of variance examined the interaction between group and time on striatal connectivity, including cluster-based thresholding to correct for multiple tests. Connectivity changes within circuits identified in group analyses were correlated with clinical change. RESULTS: Two significant group-by-time effects in the OCD group showed increased striatal connectivity from baseline to 12 weeks compared with controls. Circuits demonstrating this pattern included the right putamen with the left frontal cortex and insula and the left putamen with the left frontal cortex and pre- and post-central cortices. Increase in connectivity in the left putamen circuit was significantly correlated with clinical improvement on the Children's Yale-Brown Obsessive-Compulsive Scale score (r = -0.58, p = .03). CONCLUSION: Sertraline appears to affect specific striatal-based circuits in pediatric OCD, and these changes in part could account for clinical improvement. Future work is needed to confirm these preliminary findings, which would facilitate identification of circuit-based targets for novel treatment development. CLINICAL TRIAL REGISTRATION INFORMATION: Effects of Sertraline on Brain Connectivity in Adolescents with OCD; https://clinicaltrials.gov/; NCT02797808.
Asunto(s)
Cuerpo Estriado/fisiopatología , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/fisiopatología , Sertralina/uso terapéutico , Adolescente , Mapeo Encefálico , Estudios de Casos y Controles , Niño , Cuerpo Estriado/efectos de los fármacos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Proyectos PilotoRESUMEN
Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed.