Altered fronto-amygdalar functional connectivity predicts response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Based on findings from adults with obsessive-compulsive disorder (OCD), this study examined alterations in resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA-vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first-line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning-a probable mechanism of action of E/RP. METHODS: Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age- and sex-matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12-16-week E/RP intervention for OCD. Participants were rescanned after the 12-16-week period. ANCOVAs tested group differences in baseline rs-fc. Cross-lagged panel models examined relationships between BLA-vmPFC rs-fc and OCD symptoms pre- and posttreatment. All tests were adjusted for participants' age, sex, and head motion. RESULTS: Right BLA-vmPFC rs-fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA-vmPFC rs-fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to posttreatment. CONCLUSIONS: These results provide further evidence of the BLA-vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.

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

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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

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.

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Cognitive 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. METHODS: Twenty-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. RESULTS: Thinner 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. CONCLUSIONS: The 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.

Distinctions between autobiographical memory specificity and detail: Trajectories across cue presentations.

Autobiographical memory is central to identity and self-awareness, but individuals with depression and Post-Traumatic Stress Disorder tend to have overgeneral memories. Recent research has suggested that the ability to retrieve specific memories and individual differences in the amount of detail in specific memories are independent (Kyung, Yanes-Lukin, & Roberts, 2016). We re-analyzed data from Kyung et al. to test whether these constructs are distinct in terms of their trajectories over cue presentations. Results indicated a U-shaped trajectory for specificity, but a inverted-U trajectory for detail, suggesting a dissociation in which periods of decreasing probability of retrieving specific memories correspond to increasing amounts of detail. Further, trajectories had similar forms when memories included emotional content, but differed for recollections that did not include emotional content. Finally, at the individual level, slopes for specificity and detail across trials were uncorrelated. These findings provide further support for the independence of these constructs.

Stepped Care Interpersonal Psychotherapy Treatment for Depressed Adolescents: A Pilot Study in Pediatric Clinics.

Adolescents with depression are at risk for negative long-term consequences and recurrence of depression. Many do not receive nor access treatment, especially Latino youth. New treatment approaches are needed. This study examined the feasibility and acceptability of a stepped collaborative care treatment model (SCIPT-A) for adolescents with depression utilizing interpersonal psychotherapy for adolescents (IPT-A) and antidepressant medication (if needed) compared to Enhanced Treatment as Usual (E-TAU) in urban pediatric primary care clinics serving primarily Latino youth. Results suggest the SCIPT-A model is feasible, acceptable and potentially beneficial for urban Latino adolescents. Clinicians delivered the SCIPT-A model with fidelity using supervision successfully implemented in a community setting.

Specificity and detail in autobiographical memory: Same or different constructs?

Research on autobiographical memory has focused on whether memories are coded as specific (i.e., describe a single event that happened at a particular time and place). Although some theory and research suggests that the amount of detail in autobiographical memories reflects a similar underlying construct as memory specificity, past research has not investigated whether these variables converge. Therefore, the present study compared the proportion of specific memories and the amount of detail embedded in memory responses to cue words. Results demonstrated that memory detail and proportion of specific memories were not correlated with each other and showed different patterns of association with other conceptually relevant variables. When responses to neutral cue words were examined in multiple linear and logistic regression analyses, the proportion of specific memories uniquely predicted less depressive symptoms, low emotional avoidance, lower emotion reactivity, better executive control and lower rumination, whereas the amount of memory detail uniquely predicted the presence of depression diagnosis, as well as greater depressive symptoms, subjective stress, emotion reactivity and rumination. Findings suggest that the ability to retrieve specific memories and the tendency to retrieve detailed personal memories reflect different constructs that have different implications in the development of emotional distress.

A pilot study of Brief IPT-A delivered in primary care.

OBJECTIVE: The objective was to examine the feasibility, acceptability and preliminary effectiveness of a brief version of Interpersonal Psychotherapy for Depressed Adolescents (BIPT-A) in low-income Latino adolescents treated in an urban pediatric primary care setting. METHOD: Ten adolescents, ages 12 to 19 years, who were referred by their pediatric providers and met criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depression diagnosis participated. Participants received 6 weekly sessions of BIPT-A. Acceptability and feasibility were measured by examining session attendance, treatment completion and treatment satisfaction. Paired-samples t tests were used to preliminarily examine treatment outcome as measured by both self-report and clinician-administered assessments of depression, social functioning and global impairment. RESULTS: Ninety percent of adolescents completed treatment, with 60% of parents having participated in at least one session. Adolescents attended 82% of their treatment sessions, and all participants were very satisfied with the treatment they received. Significant improvement was found for all outcome measures. CONCLUSION: The open trial provides preliminary evidence suggesting that BIPT-A may be a feasible and acceptable treatment model capable of engaging adolescents with mild to moderate depression and impairment in treatment in a primary care setting.

Cultural Competency and Its Effect on Treatment Outcome of IPT-A in School-Based Health Clinics.

BACKGROUND: This paper assesses acculturation and ethnic matching of therapist and patient as predictors and moderators of treatment outcome in a 12-week effectiveness study of Interpersonal Psychotherapy for depressed adolescents (IPT-A) versus treatment as usual (TAU). The treatment was delivered in school-based health clinics in which care was provided for a predominantly Latino patient population. METHODS: Birthplace, length of residence in the United States (U.S.), and therapist-patient ethnic matching were examined as predictors and moderators of treatment outcomes for depression, social functioning, and global functioning scores. RESULTS: Birthplace significantly moderated treatment condition in predicting week 12 depression severity and improvement, and marginally significantly moderated treatment in predicting week 12 depression symptoms, with U.S.-born adolescents who received IPT-A having better outcomes. Birthplace predicted week 12 self-reports of depression, social (overall, school, and family) and global functioning, with U.S.-born adolescents faring worse across treatment conditions. Foreign-born adolescents treated with IPT-A as compared to TAU who lived for a longer period of time in the U.S. demonstrated better overall social functioning as compared to foreign-born adolescents who had lived for a shorter period of time in the U.S. Ethnic matching predicted significant reduction in depression severity and improved overall social functioning, and marginally significant improvement in week 12 depression scores, regardless of treatment condition. CONCLUSIONS: IPT-A may be a culturally responsive treatment for depressed Latino youth who are struggling with acculturation issues that affect their significant relationships. Ethnic matching appears beneficial for the general population in reducing depression and improving social functioning.