Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder

Abstract

Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12-16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.

Trial registration: ClinicalTrials.gov NCT02421315.

Figures

Fig. 1. Schematic of the initial path models relating functional connectivity and obsessive–compulsive disorder (OCD) symptoms before and after cognitive-behavioral therapy (CBT) treatment.

Covariances on endogenous variables refer to covariances on error terms of those variables.

Fig. 2. Edges showing significant difference between participants with obsessive–compulsive disorder (OCD) and healthy controls (HC) in functional connectivity at baseline.

a Significant edges according to both methods of correction for Type I error (i.e., false discovery rate (FDR) and network-based statistics (NBS)), along with boxplots displaying the distribution of connectivity strength (Fisher’s r-to-z scores) in each group (circles on the boxplots indicate score > 1.5 × interquartile range [IQR] and diamonds indicate score > 3 × IQR). b Significant edges according to either correction method (i.e., FDR or NBS). Blue lines on brain overlays indicate HC > OCD and red color line indicates OCD > HC. The labels are based on the Cortical Area Parcellation from Resting-State Correlations data set (Gordon et al. [66]).

Fig. 3. Cross-lagged panel results relating obsessive–compulsive disorder (OCD) symptoms and functional connectivity before and after cognitive-behavioral therapy (CBT) treatment.

*p < 0.05, **p < 0.01, ***p < 0.001. OCD symptoms are based on scores from the Children’s Yale-Brown Obsessive–Compulsive Scale. Functional connectivity represents the Fisher’s r-to-z scores between a default mode network (DMN) region (i.e., left angular gyrus; label default 7) and a frontoparietal network (FPN) region (i.e., left rostral middle frontal gyrus; label frontoparietal 9) based on the Cortical Area Parcellation from Resting-State Correlations dataset (Gordon et al. [66]). Regression parameters represent standardized estimates. Covariances between endogenous terms refer to covariances on the error terms of those variables. Values on covariances represent correlations.