Dataset Information

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression.

ABSTRACT: BACKGROUND:Early childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known. METHODS:We measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) treatment or waitlist (WL) control condition. RESULTS:Analyses included reward positivity (RewP) data from 118 children randomized to PCIT-ED treatment (n = 60) or WL control condition (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 PCIT-ED treatment vs. 55 WL control condition) at baseline. Children in the PCIT-ED group showed a greater reduction in anhedonia (F1,103 = 10.32, p = .002, partial ?2 = .09). RewP reward responses increased more (F1,87 = 5.45, p = .02, partial ?2 = .06) for PCIT-ED and a greater change in RewP was associated with a greater reduction in major depressive disorder symptoms (r = -.24, p = .05). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in the PCIT-ED group (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03). CONCLUSIONS:The ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures were associated with a greater reduction in depression, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

SUBMITTER: Barch DM

PROVIDER: S-EPMC6499710 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression.

Barch Deanna M DM Whalen Diana D Gilbert Kirsten K Kelly Danielle D Kappenman Emily S ES Hajcak Greg G Luby Joan L JL

Biological psychiatry 20181204 10

<h4>Background</h4>Early childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known.<h4>Methods</h4>We measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Paren ...[more]

PMID: 30583852

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Project description:The endocannabinoid system has been implicated in stress adaptation and the regulation of mood in rodent studies, but few human association studies have examined these links and replications are limited.To examine whether a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood physical abuse on lifetime anhedonia and depression and to replicate this interaction in an independent sample.Genetic association study in 1041 young US women with replication in an independent Australian sample of 1428 heroin-dependent individuals as cases and 506 participants as neighborhood controls.Self-reported anhedonia and depression (with anhedonia).In both samples, individuals who experienced childhood physical abuse were considerably more likely to report lifetime anhedonia. However, in those with 1 or more copies of the minor allele of rs1049353, this pathogenic effect of childhood physical abuse was attenuated. Thus, in participants reporting childhood physical abuse, although 57.1% of those homozygous for the major allele reported anhedonia, only 28.6% of those who were carriers of the minor allele reported it (P=.01). The rs1049353 polymorphism also buffered the effects of childhood physical abuse on major depressive disorder; however, this influence was largely attributable to anhedonic depression. These effects were also noted in an independent sample, in which minor allele carriers were at decreased risk for anhedonia even when exposed to physical abuse.Consistent with preclinical findings, a synonymous CNR1 polymorphism, rs1049353, is linked to the effects of stress attributable to childhood physical abuse on anhedonia and anhedonic depression. This polymorphism reportedly resides in the neighborhood of an exon splice enhancer; hence, future studies should carefully examine its effect on expression and conformational variation in CNR1, particularly in relation to stress adaptation.

Project description:BackgroundApproximately half of depressed adolescents fail to respond to cognitive behavioral therapy (CBT). Given the variability in response, it is important to identify pretreatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive versus poor outcome to CBT may have important clinical implications (e.g., informing treatment recommendations). Emerging evidence suggests that neural reward responsiveness represents one promising predictor.MethodsAdolescents with major depressive disorder (n = 36) received CBT and completed a reward task at 3 time points (pretreatment, midtreatment and posttreatment) while 128-channel electroencephalographic data were acquired. Healthy control participants (n = 29) completed the same task at 3 corresponding time points. Analyses focused on event-related potentials linked to 2 stages of neural processing: initial response to rewards (reward positivity) and later, elaborative processing (late positive potential). Moreover, time-frequency analyses decomposed the reward positivity into 2 constituent components: reward-related delta and loss-related theta activity.ResultsMultilevel modeling revealed that greater pretreatment reward responsiveness, as measured by the late positive potential to rewards, predicted greater depressive symptom change. In addition, a group × condition × time interaction emerged for theta activity to losses, reflecting normalization of theta power in the group with major depressive disorder from baseline to posttreatment.ConclusionsAn event-related potential measure of sustained (late positive potential)-but not initial (reward positivity)-reward responsiveness predicted symptom improvement, which may help inform which depressed adolescents are most likely to benefit from CBT. In addition to alleviating depression, successful CBT may attenuate underlying neural (theta) hypersensitivity to negative outcomes in depressed youths.

Dataset Information

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression.

Publications

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression.

Similar Datasets

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