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Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive-compulsive disorder.

ABSTRACT: BACKGROUND:Intensive cognitive-behavioral therapy (CBT) can effectively reduce symptoms in obsessive-compulsive disorder (OCD). However, many relapse after treatment. Few studies have investigated biological markers predictive of follow-up clinical status. The objective was to determine if brain network connectivity patterns prior to intensive CBT predict worsening of clinical symptoms during follow-up. METHODS:We acquired resting-state functional magnetic resonance imaging data from 17 adults with OCD prior to and following 4?weeks of intensive CBT. Functional connectivity data were analyzed to yield graph-theory metrics. We examined the relationship between pre-treatment connectome properties and OCD clinical symptoms before and after treatment and during a 12-month follow-up period. RESULTS:Mean OCD symptom decrease was 40.4?±?16.4% pre- to post-treatment (64.7% responded; 58.8% remitted), but 35.3% experienced clinically significant worsening during follow-up. From pre- to post-treatment, small-worldness and clustering coefficient significantly increased. Decreases in modularity correlated with decreases in OCD symptoms. Higher pre-treatment small-world connectivity was significantly associated with worsening of OCD symptoms during the follow-up period. Psychometric and neurocognitive measures pre- and post-treatment were not significant predictors. CONCLUSION:This is the first graph-theory connectivity study of the effects of CBT in OCD, and the first to test associations with follow-up clinical status. Results show functional network efficiency as a biomarker of CBT response and relapse in OCD. CBT increases network efficiency as it alleviates symptoms in most patients, but those entering therapy with already high network efficiency are at greater risk of relapse. Results have potential clinical implications for treatment selection.

SUBMITTER: Feusner JD

PROVIDER: S-EPMC4438601 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive-compulsive disorder.

Feusner Jamie D JD Moody Teena T Lai Tsz Man TM Sheen Courtney C Khalsa Sahib S Brown Jesse J Levitt Jennifer J Alger Jeffry J O'Neill Joseph J

Frontiers in psychiatry 20150520

<h4>Background</h4>Intensive cognitive-behavioral therapy (CBT) can effectively reduce symptoms in obsessive-compulsive disorder (OCD). However, many relapse after treatment. Few studies have investigated biological markers predictive of follow-up clinical status. The objective was to determine if brain network connectivity patterns prior to intensive CBT predict worsening of clinical symptoms during follow-up.<h4>Methods</h4>We acquired resting-state functional magnetic resonance imaging data f ...[more]

PMID: 26042054

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Project description:BackgroundCognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD.MethodsTwenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix.ResultsThinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness.ConclusionsThe current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.

Project description:BACKGROUND AND OBJECTIVES:This study examined the occurrence of sudden gains (or reversal of gains) among children with obsessive-compulsive disorder (OCD) during the course of cognitive-behavioral therapy (CBT), as well as the association of sudden gains with treatment response, treatment group, and pre-treatment clinical characteristics. METHODS:The sample consisted of 136 youth (ages 7-17) with a primary diagnosis of OCD who were randomized in a double-blinded fashion to 10 sessions of CBT with augmentation of either d-cycloserine or placebo. Sudden gain status was determined based on clinician-rated obsessive-compulsive symptom severity, which was collected on 9 occasions across the study period. RESULTS:42.6% of youth experienced at least one sudden gain, which tended to occur either after starting exposure and response prevention or towards the end of treatment. After applying the Benjamini-Hochberg procedure for multiple comparisons, there were no significant pre-treatment predictors of sudden gains and only reduced insight predicted the reversal of gains. Individuals with at least one sudden gain had improved overall treatment outcomes, measured both by reduction in OCD symptom severity, and by global illness severity. LIMITATIONS:Several clinical constructs were not examined. Symptomatology was not assessed at every treatment session. Differences in those who achieved sudden gains and those who did not may be obscured. There is the possibility that a sudden gain reflected a scoring error generated by an optimistic or inaccurate report. Finally, a relatively homogenous sample may limit the generalizability of results. CONCLUSIONS:The course of CBT for pediatric OCD is variable with many children experiencing sudden gains, but a sizable percentage experience a reversal of gains which was related to reduced insight. Sudden gains tended to occur after starting exposure and response prevention and towards the end of treatment. TRIALSREGISTRATION:ClinicaltrialsgovRegistry:NCT00864123. https://www.clinicaltrials.gov/ct2/show/NCT00864123.

Dataset Information

Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive-compulsive disorder.

Publications

Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive-compulsive disorder.

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