Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum

项目总结

Project Summary Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum Opioid use disorder 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. 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 expectant mothers. However, the effects of BT on maternal neurobiology and infant-oriented behaviors are unknown. Preclinical maternal brain-behavior research and human brain magnetic resonance imaging (MRI) studies have provided a model of corticolimbic maternal caregiving neurocircuits (MCN) for parenting and offspring survival. The MCN includes two reciprocally modulating systems for (1) maternal caregiving, mediated by the hypothalamic medial preoptic area (mPOA), ventral tegmental area (VTA), nucleus accumbens (NAc) and ventral pallidum; and (2) maternal defensive/aggressive behaviors, mediated by periaqueductal grey (PAG). For humans, the MCN regulates flexible responses to the demands of their own infant during adaptation to the early postpartum period - such as to the unique, ethologically salient own-baby cry. We aim to examine the human MCN and maternal behaviors in a group of opioid-dependent mothers undergoing BT (n=80), as compared to non-opioid using Depression Matched Controls (MC, n=80). All participant will have 2 MRI scans: T1 at 1-month postpartum and T2 at 4-month postpartum. The drug use and moods in all participants will be assessed at these two time points. We will combine multimodal neuroimaging methods, including functional responses to own-baby cry, gray matter volumes and resting state activity with assessments of maternal caregiving thoughts and behaviors – including measures of sensitivity and hostility – at T1 and T2. Based on our preliminary research and preclinical models we hypothesize that BT increases caregiving MCN responses to own vs. other-baby cry and such effects are linked to maternal caregiving thoughts and behaviors. We predict that T1 to T2 plastic adaptation in the MCN will be affected by BT - such that BT may interfere with normally opposing caregiving and defense subsystems of the MCN. Our controls will include recruitment of depression matched participants and statistical control for maternal childhood aversity, polysubstance use and offspring neonatal abstinence syndrome. Finally, we will explore the effects of these factors on brain and maternal behaviors within the group of BT-treated mothers. The proposed research will elucidate the effects of BT on the neurobiology of parenting - with translational potential to optimize current approaches and suggest directions to best manage postpartum mental health issues and improve mother-child bonding and child outcomes - a brain based biomarker.