Major Depressive Disorder (MDD) is a prevalent and debilitating psychiatric illness. Having a mother with MDD is a significant risk factor for MDD. A central process implicated in MDD transmission is emotion dysregulation, which results from a combination of irregular emotional reactions and maladaptive emotion regulation (ER; the ability to alter one?s emotional experience and expression in an adaptive way). Prior studies have shown that ? in response to negative stimuli ? adolescents with familial MDD risk display increased activation in brain regions associated with negative affect (NA; e.g., amygdala), and decreased activity in regions related to cognitive control (e.g., dorsolateral prefrontal cortex [dlPFC]). In response to positive stimuli, at-risk adolescents show blunted response in regions related to reward processing (e.g., ventral striatum) and increased activation in regions related to cognitive control. Together, these findings support the idea that emotion dysregulation is a risk factor for MDD. Conversely, adaptive ER may serve as a protective factor. Thus, emotion dysregulation is an important target for research and intervention. Prior imaging studies, however, suffer from low ecological validity. The present study will address this limitation in two ways. First, we will focus on interpersonal context, which is central to MDD risk. The few studies that used social stimuli examined only responses to peer feedback, despite the evidence that parental feedback is crucial in MDD. The present study will be the first to examine neural responses to both maternal and peer feedback using functional magnetic resonance imaging (fMRI). Second, we will complement fMRI with experience sampling methods (ESM), a highly ecologically valid procedure that involves monitoring individuals in daily life. Thus, the proposed study will uniquely shed light on the associations between neural responses to maternal and peer feedback and everyday experiences. We will recruit 60 never-disordered children (aged 9-13) of mothers with (high-risk) or without (low-risk) past MDD. Participants will complete an fMRI task assessing responses to peer and maternal feedback. Then, we will use ESM for 21 days to assess their emotional reactivity and regulation in response to interpersonal events. We hypothesize that (1) those at high (vs. low) risk will respond to criticism with greater activation in brain regions related to NA and less activation in regions related to cognitive control, whereas in response to praise, they will show less activation in brain regions related to reward circuitry and increased activity in regions related to cognitive control. (2) In response to everyday negative events, high-risk adolescents will experience more NA and use more maladaptive ER and less adaptive ER; in response to positive events, high-risk adolescents will experience less positive affect (PA) and use more maladaptive ER and less adaptive ER. (3) Neural responses to feedback will predict NA, PA, ER, and depressive symptoms in everyday life, and will (4) moderate within-person associations between interpersonal events and affect. (5) Gender will be used as an exploratory moderator across analyses.

Public Health Relevance

Depression is a highly prevalent and debilitating disease, with enormous personal and societal costs. The present study uses a combination of neuroimaging and experience sampling methods (ESM) to examine whether neural responses to maternal and peer feedback are related to emotional reactivity, emotion regulation, interpersonal experiences, and depressive symptoms in the everyday lives of adolescents at high vs. low familial risk for depression. Emotion regulation is known to be malleable, and therefore is a promising target for future intervention and prevention programs.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Psychosocial Development, Risk and Prevention Study Section (PDRP)
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Murphy, Eric Rousseau
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Yale University
Schools of Arts and Sciences
New Haven
United States
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