Dissecting Responses to Alcohol in Individuals with Familial Risk for Bipolar Disorder

酒精反应的个体差异可能会识别出患有酒精使用障碍风险的个体 （AUD）。这一领域的研究主要排除了患有精神障碍的个人， 这种关联的普遍性。双相情感障碍在所有精神病诊断中有最高的AUD率 缺乏对导致这种并发症的机制的研究。鉴于高基因 双相情感障碍和AUD的负荷，家族危险因素可能有助于他们的共病的出现。 在双相情感障碍和AUD中显示重叠的几个基因也被认为是 对酒精反应的个体差异。具有AUD家族史的个体表现出改变的反应 酒精，这可能会发现那些发展AUD的风险增加。尚不清楚双相情感障碍的家族风险 这种疾病与对酒精的敏感性改变有关，这反过来可能会导致 发展为合并AUD。这个R21应用程序提出了一个初步的研究，开始解剖如何家族性 危险因素导致双相情感障碍患者发生AUD风险的个体差异。具体地说， 对酒精的反应和相关的酒精使用模式将在100名年轻人（同样 除以双相情感障碍的家族风险，而不是AUDs，双相情感障碍的家族风险和AUDS，家族风险 对于AUD而不是双相情感障碍，并且通常发展为年龄和性别匹配的年轻成年人）。我们假设 双相情感障碍的家族风险与酒精反应的改变有关，通过这种机制， 增加AUD风险。这将通过两个目标进行测试：（目标1）确定对酒精反应的差异 （特别是透皮酒精浓度[TAC]，心率，身体摇摆和自我报告的差异） 目的2：评估双相情感障碍和/或AUDs家族风险个体中 双相情感障碍家族风险个体对酒精和酒精使用模式的反应。拟议 研究，年轻人将临床表型和家族史和最近的酒精和药物使用模式 评估。然后在模拟酒吧实验室中遵循标准饮料管理程序，参与者将 在酒精影响下对酒精的生理和主观反应的完整测量，或 安慰剂（人内，平衡）和佩戴酒精生物传感器，连续测量TAC。 我们预测双相情感障碍的家族风险，与AUD的家族风险相比，没有家族风险亚组将 显示达到峰值TAC的时间更短、峰值TAC更高、吸收和消除速率更快。我们预测 TAC变量的差异将与具有家族性风险的个体的危险酒精使用模式相关， 躁郁症将研究对酒精反应的其他措施的差异，并研究与TAC的关系。 检查的措施。这项R21奖是确定可能有助于实现以下目标的机制的关键第一步： 双相情感障碍患者AUD风险升高。这些发现可以为早期发现风险提供新的，具体的目标， 预防和治疗双相情感障碍更具体和有效。

Individual differences in alcohol responses may identify individuals at risk for developing alcohol use disorders (AUDs). Research in this field has predominantly excluded individuals with psychiatric disorders limiting the generalizability of this association. Bipolar disorder has the highest rate of AUDs of any psychiatric diagnosis yet there is a paucity of study investigating mechanisms that contribute to this comorbidity. Given the high genetic load of both bipolar disorder and AUDs, familial risk factors likely contribute to the emergence of their comorbidity. Several of the genes showing overlap in bipolar disorder and AUDs have also been suggested to underlie individual differences in response to alcohol. Individuals with a family history of AUDs exhibit altered responses to alcohol, which may identify those at increased risk for developing AUDs. It is unknown if familial risk for bipolar disorder is associated with altered sensitivity to alcohol which in turn may contribute to elevated risk for developing comorbid AUDs. This R21 application proposes a preliminary study to begin dissecting how familial risk factors contribute to individual differences in risk for developing AUDs in bipolar disorder. Specifically, responses to alcohol and associated alcohol use patterns will be investigated in 100 young adults (equally divided by familial risk for bipolar disorder but not AUDs, familial risk for bipolar disorder and AUDS, familial risk for AUDs but not bipolar disorder, and typically developing age- and sex- matched young adults). We hypothesize that familial risk for bipolar disorder is associated with altered responses to alcohol and, through that mechanism, increased risk for AUDs. This will be tested through two aims: (Aim 1) identify differences in responses to alcohol (specifically differences in transdermal alcohol concentration [TAC], heart rate, body sway, and self-report of intoxication) in individuals with familial risk for bipolar disorder and/or AUDs and (Aim 2) assess relations between responses to alcohol and alcohol use patterns in individuals with familial risk for bipolar disorder. In the proposed research, young adults will be clinically phenotyped and family history and recent alcohol and drug use patterns assessed. Then following standard beverage administration procedures in a simulated bar lab, participants will complete measures of physiological and subjective responses to alcohol while under the influence of alcohol or a placebo (within-person, counter-balanced) and wearing an alcohol biosensor that continuously measures TAC. We predict familial risk for bipolar disorder, compared to familial risk for AUDs and no familial risk subgroup will show a shorter time to reach peak TAC, higher peak TAC, and faster absorption and elimination rates. We predict differences in TAC variables will be associated with risky alcohol use patterns in individuals with familial risk for bipolar disorder. Differences in other measures of response to alcohol will be investigated and relations with TAC measures examined. This R21 award is a critical first-step to identifying mechanisms that may contribute to elevated risk for AUDs in bipolar disorder. Findings could inform new, specific targets for early detection of risk, prevention, and treatment that are more specific and effective in bipolar disorder.