Brain imaging of appetitive decision making in alcohol dependent young women

描述（由申请人提供）：大量饮酒的妇女也更有可能从事危险的生殖行为，增加她们意外怀孕、人际传播感染的可能性（Leigh, 1999； O'Hare, 1998）和胎儿酒精暴露（Streissguth etal ., 1994）。美国国家酒精滥用和酒精中毒研究所最近报告说，大学生间歇性酗酒的情况有所增加（Hingson等人，2009年）。了解年轻育龄妇女的食欲决定可以为这一日益危险的群体提供适当的干预措施。特别是，需要更具体的知识来了解酒精和大脑过程之间的相互作用，这些过程可能会导致依赖酒精的女性倾向于冒险行为。青年期不仅是繁殖最频繁的时期，而且是酒精依赖和潜在决策能力的额叶神经系统发育的关键时期，这表明这两个发育过程之间可能存在相互作用。目前的研究调查了一种假设，即前额叶边缘系统的功能性神经解剖学改变是酒精滥用和危险生殖行为之间的重要联系。此外，女性的荷尔蒙状态可能是调节酒精和大脑相互作用的一个相关因素，可能会给年轻女性和她们潜在的后代带来严重的脆弱性。最近的证据表明，在女性的月经周期中，前额叶边缘奖励系统在食欲决策过程中的功能是不同的（Rupp et al, 2009）。具体来说，与月经周期的黄体期相比，女性在排卵期评估新男性面孔时，在眶额皮质中表现出更多的神经激活。我们假设，一般来说，依赖酒精的年轻女性的大脑回路更敏感，而接近排卵的荷尔蒙状态进一步增强了她们冒险的脆弱性。我们将使用功能性磁共振成像（fMRI）检查20名酒精依赖和20名非酒精依赖的年轻女性对奖励刺激（包括酒精、男性面孔和食物的图片）的神经激活模式。为了测试荷尔蒙状态的影响，我们将在月经周期的两个阶段对自然周期的女性进行测试，包括在女性最有可能怀孕的卵泡期。我们预测，依赖酒精的女性在与奖励相关的大脑区域会表现出更大的神经激活，而在与行为抑制相关的大脑区域则会表现出更少的激活，而且这种差异在排卵期间会特别明显。平衡潜在的欲望环境和伴侣的风险和回报的能力对于年轻女性及其潜在后代的安全至关重要。了解月经周期与酒精依赖和非酒精依赖女性的神经激活和生殖决策之间的相互作用，可以增强我们的干预能力，促进处于危险中的年轻女性更安全的食欲行为。

DESCRIPTION (provided by applicant): Women who consume large amounts of alcohol are also more likely to engage in risky reproductive behavior, increasing their likelihood of unplanned pregnancies, interpersonally transmitted infections (Leigh, 1999; O'Hare, 1998), and fetal alcohol exposure (Streissguth et al., 1994). The National Institute on Alcohol Abuse and Alcoholism recently reported an increase in heavy episodic drinking in college students (Hingson et al., 2009). Understanding appetitive decision-making in young women of reproductive age could inform appropriate intervention for this increasingly at-risk group. In particular, more specific knowledge is needed regarding the interaction between alcohol and the brain processes underlying motivated decision making that may bias alcohol-dependent women towards risky behavior. Young adulthood is a critical time during which not only reproduction most often occurs, but alcohol dependence and frontal neural systems underlying decision making develop, suggesting a possible interaction between the two developmental processes. The current study investigates the hypothesis that altered functional neuroanatomy of the prefrontal-limbic system is an important link between alcohol abuse and risky reproductive behavior. Furthermore, a woman's hormonal state is likely to be a relevant factor mediating alcohol and brain interactions, possibly creating windows of acute vulnerability for young women and their potential offspring. Recent evidence suggests that the prefrontal-limbic reward system differs functionally across a woman's menstrual cycle during appetitive decision-making (Rupp et al., 2009). Specifically, women evaluating novel male faces exhibited more neural activation in the orbitofrontal cortex when tested during ovulation as compared to the luteal phase of the cycle. We hypothesize that alcohol-dependent young women have a more sensitized reward brain circuitry in general, and that the hormonal state close to ovulation further enhances vulnerability to risk taking. Using functional magnetic resonance imaging (fMRI) we will examine the neural activation patterns of 20 alcohol-dependent and 20 nondependent young women in response to rewarding stimuli, including pictures of alcohol, male faces, and food. In order to test for effects of hormonal status, we will test naturally cycling women at two phases across their menstrual cycles, including during the follicular phase when a woman is most likely to conceive. We predict that alcohol-dependent women will demonstrate greater neural activation in brain regions associated with reward and less activation in brain regions related to behavioral inhibition, and that the difference will be especially pronounced around ovulation. The ability to balance between the risk and reward of potential appetitive situations and partners is imperative for the safety of young women and their potential offspring. An understanding of menstrual cycle interactions with neural activation and reproductive decision making in alcohol-dependent and non dependent women can enhance our ability to intervene to promote safer appetitive behavior in at-risk young women. PUBLIC HEALTH RELEVANCE: Young alcohol-dependent women demonstrate changes in brain function that may bias them towards risky reproductive decision-making. Unplanned pregnancies in women who consume large amounts of alcohol have long-term negative consequences for infants prenatally exposed to alcohol. An understanding of the functional neuroendocrinological changes that occur with alcohol-dependence, such as sensitization of neural systems associated with the appraisal of risk and reward, are critical to promote optimal appetitive decision-making in young women of reproductive age to protect them and their offspring from the adverse effects of alcohol exposure.