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

Abstract

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 learninga 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 rsfc 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. K E Y W O R D S biological markers, child and adolescent, cognitive behavioral therapy (CBT), functional magnetic resonance imaging (fMRI), obsessive-compulsive disorder (OCD) Moira A. Rynn and Rachel Marsh are joint senior authors.samples should replicate and extend these findings that may ultimately lead to treatment targets for future circuit-based interventions aimed at improving fear extinction (and adaptive learning in general) in youth with OCD or subclinical OC symptoms.

Aberrant cerebellar-cerebral functional connectivity in patients with obsessive-compulsive disorder, and its trajectory after pharmacotherapy and potential for diagnosis and prediction of early treatment effects

“…Nabeyama et al observed that less activation in the cerebellum of patients with OCD than HCs during the Stroop task was increased after a 12-week behavior therapy [71]. Cyr et al found that the FC between the right basolateral amygdala and the ventromedial prefrontal cortex was signi cantly reduced in patients with OCD at baseline relative to HCs, and increased following a 12-16-week exposure and response prevention intervention [72]. The normalizations of cerebral structure and metabolism were also observed in patients with OCD who treatment with paroxetine.…”

“…et al reported that greater raphe nucleus-left MTG FC was positively correlated with the severity of OCD at baseline, and the larger FC of the raphe nucleus-left MTG was also found in SSRI non-responders relative to responders, which could serve as a predictor of SSRI response after 16 weeks[80]. Altered network connectivity could also predict response to cognitive behavioral therapy[35,72,[81][82][83], exposure therapy [84, 85], continuous theta burst stimulation [86], or deep brain stimulation [87] in patients with OCD. Multivariate analysis, i.e., SVR and SVM, better re ected the temporal and spatial patterns of brain networks than conventional univariate methods.…”

Subcortical shape in pediatric and adult obsessive‐compulsive disorder

“…Thus, this secondary data analysis focused on N = 200 participants with usable structural MRI: Study 1 (R21MH093889; MPIs: R. M., H. B. S.) included 66 adults (33 OCD; 33 healthy, 18–52‐year‐olds), Study 2 (R01MH104648; MPIs: R. M., H. B. S.) included 79 adults (42 OCD; 37 healthy, 18–55‐year‐olds), and Study 3 (R21MH101441; MPIs: R. M., M. A. R.) included 55 children and adolescents (28 OCD; 27 healthy, 5–18‐year‐olds). Prior structural and functional MRI findings from these studies are published elsewhere (Cyr et al, 2020, 2021; DeSerisy et al, 2021; Marsh et al, 2014, 2015; Pagliaccio et al, 2019; Posner et al, 2014; Shi et al, 2021).…”

“…M., M. A. R.) included 55 children and adolescents (28 OCD; 27 healthy, 5-18-year-olds). Prior structural and functional MRI findings from these studies are published elsewhere (Cyr et al, 2020(Cyr et al, , 2021DeSerisy et al, 2021;Marsh et al, 2014Marsh et al, , 2015Pagliaccio et al, 2019;Posner et al, 2014;Shi et al, 2021).…”

Anatomical distance affects functional connectivity at rest in medicine-free obsessive–compulsive disorder

“…A considerable number of resting-state functional magnetic resonance imaging (RS-fMRI) studies have reported that OCD may result from altered large-scale brain networks rather than from a single brain region [ 2 – 4 ]. Functional connectivity (FC) is an index for characterizing temporal and spatial functional communication among different brain regions, and has been widely used in OCD [ 5 – 7 ]. Previous studies used region-of-interest (ROI) seed-based FC and independent component analysis (ICA) approaches to evaluate FC changes in specific regions/networks [ 8 – 10 ].…”