This proposed competitive supplement/revision extends the aims of this ongoing randomized controlled trial of Parent Child Interaction Therapy Emotion Development (PCIT-ED) by adding complimentary neural measures of three core emotion domains that are directly targeted by the treatment. This includes hedonic tone measured by reward processing and negative emotion reactivity measured by response to loss/lack of reward as well as emotion regulation. PCIT-ED is an early psychotherapeutic intervention for preschool depression that directly targets emotion reactivity, hedonic tone and emotion regulation. These emotion domains are measured behaviorally in the ongoing RCT, but this supplement will allow a unique investigation of the neural correlates of these constructs. The treatment is designed to target these emerging components of emotion development, known to be altered in preschool depression, by acting through the parent child relationship during this period of relatively greater neuroplasticity and rapid developmental change. The Research Domain Criteria (RDoC) provides a framework in which to identify and test core behavioral and neural dimensions contributing to altered hedonic processing and emotion reactivity and regulation associated with early onset depression. Depression is associated with both decreased responsiveness to reward and enhanced responsiveness to loss in adolescents and adults. We propose to study depressed preschoolers (PO-MDD) prior to treatment, mid-treatment and post-treatment using well-validated ERP and fMRI markers of response to reward and loss previously used to characterize depression related alterations in these domains. We will test the hypotheses that behavioral and neural indicators of responsiveness to reward and loss will improve as a result of PCIT-ED, and that these neural measures will predict who is most likely to respond. Such data could provide crucial evidence of translational biomarkers of treatment efficacy and predictors of treatment response, of particular importance during this early neuroplastic developmental period. The proposed supplement will add ERP and fMRI measures of these specific constructs through the use of age appropriate paradigms, measured pre and post treatment/wait condition, to inform predictors of treatment response and potentially mechanisms of change. This add-on study is in line with the NIMH strategic plan and the RDoC initiative by investigating brain behavior relationships central to depression and targeting them early in development. The ongoing R01 is the first large scale RCT of an early intervention for depression to our knowledge and therefore provides an unprecedented opportunity to investigate changes in affective systems in very young children from both behavioral and neural perspectives. We include both ERP and fMRI to determine whether these complementary measures identify unique or overlapping variance in the neural correlates/mechanisms of change and/or the predictors of treatment response.
This project has high relevance for public health by developing biomarkers of brain function that are related to recovery of depression in early childhood. Specifically the data will help us to understand the mechanisms leading to improvement in depression and function in depressed preschoolers during Parent-Child Interaction Therapy-Emotion Development, as well as to help identify age-appropriate and feasible biomarkers that predict who is most likely to benefit from treatment.
