Project Summary R01 DA047336-01: Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum Opioid use disorder (OUD) is a fast-growing and devastating epidemic in the US, affecting a high proportion of child-bearing women, with many suffering comorbid mood disorders. Untreated opioid use and dependence may cause withdrawal symptoms, impair interpersonal interactions and may be associated with polysubstance use and neonatal abstinence syndrome (NAS). These problems are linked to higher risks of child maltreatment and costly utilization of foster care. Buprenorphine Treatment (BT) reduces withdrawal and other deleterious effects of illicit opioids for peripartum women. However, the effects of BT on maternal neurobiology and infant-oriented behaviors in the context of OUD are unknown. Preclinical maternal brain-behavior research and human brain magnetic resonance imaging (MRI) studies have provided a model of corticolimbic maternal caregiving neurocircuit (MCN) for parenting behaviors. The MCN includes two reciprocally inhibiting subsystems for (1) maternal care, mediated by the medial preoptic area in hypothalamus, ventral tegmental area, nucleus accumbens and ventral pallidum; and (2) maternal defense, mediated by periaqueductal grey. For humans, the MCN regulates flexible responses to the demands of their own infant – such as to the unique, ethologically salient own-baby cry – during the early postpartum period. We aim to examine the human MCN and maternal behaviors in a group of mothers undergoing BT for OUD (n=80) as compared to non-OUD depression Matched Controls (MC, n=80). All participant will have 2 MRI scans: T1 at 1-month postpartum and T2 at 4-month postpartum. We will measure maternal thoughts and behaviors – including measures of infant-oriented care and defense – and polysubstance use and moods in all participants. We will use multimodal neuroimaging methods to measure resting-state functional connectivity, neural responses to own-baby cry, and gray matter volumes of MCN. Based on our preliminary research and preclinical models we hypothesize that BT in OUD increases activity in both care and defense subsystems of MCN and diminishes normal reciprocal inhibition between these subsystems, resulting in potential disinhibition of maternal infant-oriented defensive thoughts and behaviors. Finally, we will explore the effects of cumulative buprenorphine exposure (daily dosage x days on BT) on MCN physiology and maternal behaviors within the group of BT mothers, controlling for polysubstance use and NAS. The proposed research will elucidate the effects of BT in the context of OUD on the neurobiology of parenting - with translational potential to optimize current approaches to treat mothers with OUD and suggest directions to best manage postpartum mental health issues.

Project Narrative Opioid use disorder (OUD), a significant epidemic with comorbid depression, polysubstance use and neonatal abstinence syndrome, is currently treated with buprenorphine to reduce withdrawal, effects the social emotional brain circuits of that govern maternal caregiving thoughts and behaviors and influence infant development are unknown. This interdisciplinary project will employ multimodal and longitudinal brain imaging and measure parent-infant interactions to investigate how the maternal brain adapts to the early postpartum, focusing on the effects of buprenorphine with comparison groups of depression matched and healthy controls. The completion of this grant will yield brain-based biomarkers connected with inexpensive measures that will contribute to improved assessment and treatment of families suffering OUD, their children and society - which ultimately bears much of the cost for the common trans-generational problems of peripartum drug use.