Oxytocin and Brain Reward and Stress Responses to Infant Cues in Addicted Mothers

 母亲吸毒成瘾是妇女和受影响儿童的一个主要公共卫生问题，对儿童的社会、情感和认知发展产生长期影响。目前的治疗策略往往侧重于母亲和她目前的成瘾，而不是她与孩子的关系，以及可能使成瘾问题持续存在的发展过程，如未解决的童年依恋创伤，忽视和慢性压力。与那些发现与自己的婴儿接触是一种独特的有益体验的母亲不同，成瘾的母亲可能不太能够对婴儿的暗示做出适当的反应，发现它们本质上不那么值得或突出，而且更容易引起压力。我们目前的研究已经确定了多巴胺能和催产素能脑通路中的关键区域，与非成瘾母亲相比，当成瘾母亲看到自己与未知婴儿的面孔时，这些区域显示出功能性MRI反应减弱。这些区域包括下丘脑、纹状体和腹内侧前额叶皮层。催产素是一种神经肽，在成瘾的母亲中外周水平降低，与母亲的大脑和行为反应密切相关。当鼻内给药时，我们的试验数据显示纹状体、前额皮质和杏仁核的激活增强。该更新补助金的目的是继续和扩大我们对母体成瘾的研究，通过进行鼻内催产素对母体脑反应的随机、双盲、安慰剂对照、交叉研究。将从我们目前的两个研究中心（贝勒医学院和耶鲁儿童研究中心）招募一组新的150名母亲（75名有吸毒史的母亲和75名匹配的对照母亲），沿着她们4至7个月大的婴儿，参加为期两个月的四次研究访视。在第1次访视期间，母亲将完成成人依恋访谈，以确定其依恋分类，并确定未解决创伤的标志物。在访视2时，将进行母婴互动的录像自由游戏评估（CARE指数）和改良的静止面部程序，以评估产妇分娩和同步性的质量。在最后两次研究访视期间，功能性MRI将用于比较接受鼻内催产素或安慰剂后母体大脑对婴儿面部线索的反应，比较“自己的”与“未知的”快乐和悲伤的面孔。我们将集中在激活，功能之间的连接，纹状体，前额叶皮层和杏仁核，关键的奖励和压力相关的地区含有催产素神经元连接。我们还将研究可能缓和催产素在大脑中的作用的因素，包括依恋分类，母婴同步，寻求感觉或冒险行为，以及压力/创伤暴露。这些知识将大大有助于我们的长期目标，即为患有药物依赖和成瘾的母亲发现新的治疗策略。

 DESCRIPTION (provided by applicant): Maternal drug addiction constitutes a major public health problem for both women and affected children, with long lasting consequences on children's social, emotional and cognitive development. Current treatment strategies tend to focus on the mother and her current addiction, rather than her relationship with her child, and developmental processes that may perpetuate the addiction problems, such as unresolved childhood attachment trauma, neglect, and chronic stress. Unlike mothers who find engaging with their own infant to be a uniquely rewarding experience, mothers with addictions may be less able to respond appropriately to their infant's cues, finding them less intrinsically rewardin or salient, and more stress provoking. Our current study has identified key areas in dopaminergic and oxytocinergic brain pathways that show a diminished functional MRI response when addicted mothers view the faces of their own vs. unknown infants, compared with non- addicted mothers. These areas include the hypothalamus, striatum and ventromedial prefrontal cortex. Oxytocin, a neuropeptide with decreased peripheral levels seen in addicted mothers, is integrally involved in maternal brain and behavioral responses. When administered intranasally, our pilot data has shown enhanced activation of the striatum, prefrontal cortex and amygdala. The purpose of this renewal grant is to continue and expand upon our investigation of maternal addiction, by conducting a randomized, double-blinded, placebo- controlled, crossover study of intranasal oxytocin on maternal brain responses. A new group of 150 mothers from our two current study sites (Baylor College of Medicine and the Yale Child Study Center) will be enrolled (75 with a history of drug addiction and 75 matched control mothers), along with their 4 to 7-month-old infants, to participate in four study visits over a two-month period. During Visit 1, mothers will complete the Adult Attachment Interview to determine their attachment classification and to identify markers of unresolved trauma. At Visit 2, a videotaped free-play assessment of mother-infant interaction (the CARE-Index), and a modified Still Face Procedure, will be conducted to assess the quality of maternal caregiving and synchrony. During the final two study visits, functional MRI will be used to compare maternal brain responses to infant face cues after receiving either intranasal oxytocin or placebo, comparing "own" vs. "unknown" happy and sad faces. We will focus on activation of, and functional connectivity between, the striatum, prefrontal cortex and amygdala, key reward and stress related regions containing oxytocinergic neuronal connections. We will also examine factors that may moderate oxytocin's effect in the brain, including attachment classification, mother-infant synchrony, sensation-seeking or risk-taking behavior, and stress/trauma exposure. This knowledge will contribute significantly to our long-term goal of discovering novel treatment strategies for mothers who suffer from drug dependency and addiction.