Assessing the Influence of Oxytocin on Postpartum Depression Using Brain Imaging

描述（由申请人提供）：婴儿出生后，10-15%的女性会经历产后抑郁症（PPD） （Halbreich & Karkum, 2006）。了解产后期的基本功能神经内分泌学，包括激素介导的神经激活模式，以响应消极的唤起刺激，是必要的适当治疗。对产后以外女性抑郁症的研究表明，抑郁女性表现出前额叶边缘系统神经激活模式的改变，对负面刺激的反应性增加（Liberzon & Martis, 2006; Siegle et al., 2007）。患有产后抑郁症的女性是否也是如此尚不清楚。重要的是，前额叶边缘系统可能调节母性行为（Lorberbaum et al., 1999; Ranote et al., 2004; Seifritz et ., 2003; Swain et al., 2007）。一个可行的假设是，前额叶边缘系统在母亲的影响下发生了改变，对婴儿的刺激变得更加敏感，而对环境中消极刺激的反应则更少。已知神经肽催产素可以降低边缘系统的神经激活（Kirsch等，2005），并且在新妈妈中升高，这表明它可能对产后妇女功能反应性的变化很重要。如果前额叶边缘系统对负面刺激的反应改变对最佳母性行为至关重要，那么先前在抑郁症妇女中证明的这一回路的破坏（Herwig等人，2007；Siegle等人，2007）可能对产后妇女及其婴儿的心理健康具有重要意义。本研究拟探讨产后哺乳期非抑郁妇女是否存在催产素介导的对负性唤起刺激的神经反应的抑制，以及这种抑制是否在产后抑郁症妇女中被破坏。使用功能磁共振成像（fMRI），我们将首先表征非抑郁产后妇女对负性唤起刺激的神经激活，并将其激活与产后产后妇女PPD的神经活动进行比较。内源性催产素水平将与大脑活动相关联，以寻找两者之间的联系。为了研究大脑中催产素作用对女性对负面刺激反应的潜在原因，我们还将测量给予外源性鼻腔催产素喷雾的女性的神经激活。具体来说，36名未分娩妇女、36名产后无抑郁妇女和36名产后抑郁妇女的大脑活动将被比较她们对消极唤起图片的反应。在这三组中，每组有12名女性将在没有干预的情况下接受测试，12名女性将接受安慰剂鼻腔喷雾剂，12名女性将在功能磁共振成像扫描前接受鼻腔催产素喷雾剂。本研究将进一步加深我们对产后神经激活模式的理解，并探讨催产素是否通过抑制边缘脑区对负性刺激的神经激活来促进产妇的最佳行为，从而缓冲女性的抑郁情绪。公共卫生相关性：母性所固有的极端社会心理和生理变化使许多妇女在婴儿出生后的一年内易患情绪障碍。母亲情绪障碍不仅对经历抑郁症的母亲有负面影响，而且对她的婴儿、伴侣和家庭也有负面影响。了解母性发生的功能性神经内分泌变化，如催产素介导的与负性情绪唤醒相关的神经活动抑制，对于促进产后期间产妇护理和保护免受情绪障碍的影响至关重要。

DESCRIPTION (provided by applicant): Following the birth of an infant, 10-15% of women experience postpartum depression (PPD) (Halbreich & Karkum, 2006). Understanding the basic functional neuroendocrinology of the postpartum period, including hormonally mediated patterns of neural activation in response to negatively arousing stimuli, is imperative for appropriate treatment. Studies of depression in women outside of the postpartum period have shown that depressed women exhibit altered prefrontal-limbic system neural activation patterns and increased reactivity to negative stimuli (Liberzon & Martis, 2006; Siegle et al., 2007). Whether the same is true of women suffering from PPD is not known. Importantly, the prefrontal-limbic system may mediate maternal behavior (Lorberbaum et al., 1999, Ranote et al., 2004; Seifritz et al., 2003; Swain et al., 2007). A working hypothesis is that the prefrontal-limbic system is altered by motherhood, becoming more sensitive to infant stimuli and less responsive to negatively arousing stimuli in the environment. The neuropeptide oxytocin is known to decrease neural activation in the limbic system (Kirsch et al., 2005) and is elevated in new mothers, suggesting that it may be important to the change in functional reactivity in postpartum women. If altered responsiveness of the prefrontal-limbic system to negative stimuli is critical for optimal maternal behavior, then the disruption of this circuitry previously demonstrated in depressed women (Herwig et al., 2007; Siegle et al., 2007) may have important implications for the mental health of postpartum women and their infants. The current study proposes to investigate whether there is an oxytocin-mediated inhibition of the neural response to negatively arousing stimuli in nondepressed postpartum breast-feeding women, and whether this inhibition is disrupted in women with PPD. Using functional magnetic resonance imaging (fMRI), we will first characterize neural activation of nondepressed postpartum women in response to negatively arousing stimuli and compare their activation to the neural activity in postpartum women with PPD. Endogenous levels of oxytocin will be correlated with brain activation to look for an association between the two. To investigate potential causation of oxytocin action in the brain on women's responses to negatively arousing stimuli, we will also measure the neural activation of women given exogenous nasal oxytocin spray. Specifically, the brain activity of 36 nulliparous women, 36 nondepressed postpartum women, and 36 depressed postpartum women will be compared in their response to negatively arousing pictures. Within each of the three groups, 12 women will be tested without intervention, 12 will receive placebo nasal spray, and 12 will receive nasal oxytocin spray prior to fMRI scanning. This study will further our understanding of neural activation patterns characteristic of the postpartum period and explore whether oxytocin buffers women against depression by inhibiting neural activation to negatively arousing stimuli in limbic brain regions to promote optimal maternal behavior. PUBLIC HEALTH RELEVANCE: The extreme psychosocial and physiological changes inherent to motherhood leave many women vulnerable to mood disorders during the year following the birth of an infant. Maternal mood disorders have negative consequences not only for the mother experiencing the depression, but also for her infant, partner, and family. An understanding of the functional neuroendocrinological changes that occur with motherhood, such as oxytocin-mediated inhibition of neural activity related to negative emotional arousal, is critical to promote optimal maternal care and protection from mood disorders during the postpartum period.