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Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety.

ABSTRACT: BACKGROUND:Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala-PFC function and anxiety symptoms across development. METHODS:Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala-PFC connectivity, as a function of early-childhood BI. RESULTS:In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala-left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety-connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety-ABV association, whereas high-BI children showed a positive anxiety-ABV association. CONCLUSIONS:Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.

SUBMITTER: Abend R

PROVIDER: S-EPMC7711072 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety.

Abend Rany R Swetlitz Caroline C White Lauren K LK Shechner Tomer T Bar-Haim Yair Y Filippi Courtney C Kircanski Katharina K Haller Simone P SP Benson Brenda E BE Chen Gang G Leibenluft Ellen E Fox Nathan A NA Pine Daniel S DS

Psychological medicine 20190108 1

<h4>Background</h4>Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinall ...[more]

PMID: 30616705

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Project description:Anxiety and obsessive-compulsive disorders are common childhood psychiatric disorders. Behavioral inhibition (BI) is a widely studied risk factor for anxiety. Less is known about overcontrol, a related behavioral phenotype characterized by concern for errors, perfectionism, and inflexibility and also associated with anxiety and obsessive-compulsive disorder. Both BI and overcontrol show associations with aberrant cognitive control and neural error responding (via the error-related negativity; ERN) yet it is unknown whether each imparts differential risk. Understanding whether overcontrol demonstrates independent associations from BI with cognitive functioning, neural error monitoring, and childhood anxiety and obsessive-compulsive presentations could aid in identifying a novel mechanistic treatment target. We assessed BI, overcontrol, cognitive functioning and psychopathology in a cross-sectional sample of 5-6 year old children (N = 126). Children completed an electroencephalogram (EEG) to assess the ERN. Overcontrol was associated with worse cognitive shifting, worse inhibitory control and higher anxiety and obsessive-compulsive symptoms, beyond BI. BI was associated with worse cognitive shifting, better inhibitory control and higher anxiety symptoms, beyond overcontrol. When assessed simultaneously, only overcontrol demonstrated a significant relationship with a blunted ERN. Moreover, overcontrol mediated (cross-sectionally) the well-established relationship between ERN and anxiety and obsessive-compulsive symptoms. BI and overcontrol impart differential risk for child cognitive functioning and anxiety while overcontrol demonstrates additional risk for aberrant neural error monitoring, anxiety and obsessive-compulsive presentations. Overcontrol may also be a mechanistic pathway between the ERN and transdiagnostic anxiety and obsessive-compulsive symptoms. Overcontrol may be a target warranted for early-childhood intervention in anxiety and OCD.

Project description:BackgroundAnxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy.MethodsIn this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12.ResultsThe percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline.ConclusionsBoth cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.)

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Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety.

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Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety.

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