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

 描述(由申请人提供)：母亲吸毒成瘾是妇女和受影响儿童的主要公共卫生问题，对儿童的社会、情感和认知发展具有长期影响。目前的治疗策略倾向于关注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永久化的发展过程，如未解决的童年依恋创伤、忽视和慢性压力。与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，患有毒瘾的母亲可能更不能对婴儿的暗示做出适当的反应，发现他们本质上不那么有成就感或显著，更容易引发压力。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，与未上瘾的母亲相比，上瘾母亲看到自己和未知婴儿的脸时，功能磁共振反应减弱。这些区域包括下丘脑、纹状体和前额叶腹内侧皮质。催产素是一种神经肽，在成瘾母亲中可见外周水平下降，它与母亲的大脑和行为反应密切相关。当鼻腔给药时，我们的试点数据显示纹状体、前额叶皮质和杏仁核的激活增强。这笔续期拨款的目的是通过进行一项随机、双盲、安慰剂对照、鼻腔内催产素对母亲大脑反应的交叉研究，继续并扩大我们对母亲成瘾的调查。来自我们目前两个研究地点(贝勒医学院和耶鲁儿童研究中心)的150名母亲将与她们4到7个月大的婴儿一起参加为期两个月的四次研究访问。在访问1期间，母亲将完成成人依恋访谈，以确定她们的依恋分类，并确定未解决的创伤的标志。在第二次访问中，将对母婴互动进行录像自由玩耍评估(CARE-Index)，并对修改后的静止面孔程序进行评估，以评估产妇照料和同步的质量。在最后两次研究访问中，功能磁共振将被用来比较母亲在接受鼻腔内注射催产素或安慰剂后，母亲的大脑对婴儿面部暗示的反应，比较“自己”和“未知”的快乐和悲伤的面孔。我们将专注于纹状体、前额叶皮质和杏仁核之间的激活和功能连接，这些区域是包含催产素能神经元连接的关键奖赏和应激相关区域。我们还将研究可能缓和催产素在大脑中的影响的因素，包括依恋分类、母婴同步性、感觉寻求或冒险行为，以及压力/创伤暴露。这些知识将对我们为患有药物依赖和成瘾的母亲发现新的治疗策略的长期目标做出重大贡献。

 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.