Project Abstract. Children of depressed mothers are at increased risk for developing multiple psychiatric disorders in their lifetime. Devastatingly, these affective and behavioral disorders appear to emerge early in these high risk youth, with some studies showing elevated rates by age 5 or 6—highlighting the need to uncover etiological mechanisms that occur in the first five years of life. One putative mechanism of risk for psychopathology is aberrant responding in reward and social circuitry that is associated with less motivation for and pleasurable enjoyment of positive experiences. However, when, how, and why these reward disruptions emerge is unclear. One possibility is that compromised caregiving during the first years of life may fail to reinforce healthy reward function in offspring, given that warm, synchronous interactions appear to serve as a social reward. The conceptual model of this proposed BRAINS award is that positive reciprocal and synchronous interactions between mother and child during the crucial infant- toddler years may serve to reinforce brain development in offspring reward systems via oxytocin- dopamine-frontostriatal pathways. For children of depressed mothers, this loop may be compromised by less synchronous interactions and the negative impact of these asynchronous interactions may have cascade effects for child social behavior, including affect regulation with and by others, perspective- taking, and empathy, and for child psychiatric illness, especially anxiety and disruptive disorders. Using a multi-method, accelerated longitudinal design, a diverse sample of 160 mothers (half meeting criteria for depression) and first-born children will be recruited into three cohorts (at child age 12 months, 24 months, and 36 months at study entry) and will be assessed yearly for three years. Mother-child synchrony during play will be assessed for each cohort yearly using affective (shared positive affect) and behavioral (harmonious, reciprocal play) indices. Simultaneous near-infrared spectroscopy (NIRS), an optical imaging technique that is non-restrictive and child-friendly will be used to measure neural responding to mother-child play in both mothers and children at all ages. Mother-child synchrony of neural responding in cortical neural regions implicated in reward responding, social flexibility, synchronous interactions, and mentalizing will also be explored. Starting at child age 3, child neural response to reward and social feedback will be assessed using developmentally-appropriate NIRS reward paradigms. At age 5, children will undergo an fMRI scan to explore activity in and connectivity among reward and social networks. Changes in child prosocial behavior and aggressive behavior and emergence of preschool psychopathology (anxiety, disruptive disorders) will be measured at child ages 3-5.Mother- child bio-behavioral synchrony will be evaluated as a predictor of these changes and the onset of disorder.