Family Study of Comorbidity of Anxiety Disorders and Sub

焦虑症及其亚型合并症的家庭研究

• 批准号: 7312922
• 负责人: kathleen r merikangas
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7312922
• 关键词: Family; Study; Comorbidity; Anxiety; Disorders

This study examined the familial transmission of anxiety disorders and substance abuse using a combination of the family study/longitudinal high risk paradigms. This study also investigated comorbidity between physical disorders and mood and anxiety disorders. The chief findings reveal specificity of familial aggregation of anxiety disorders in general and the panic and social phobia subtypes in particular. Likewise, there was familial aggregation of substance abuse, with some suggestion of specificity of specific drugs. In contrast, although there was no evidence for vertical transmission of nicotine dependence, there was an increased risk of nicotine dependence among siblings. With respect to physical disorders, it was found that anxiety disorders were most strongly associated with physical disorders in general, and that there was evidence for co-transmission of migraine with anxiety and mood disorders in families. A 10-year prospective study of the offspring of parents with these conditions was conducted in order to identify the early signs and manifestations of parental disorders. A comprehensive domain of assessments of individual, familial and social risk factors among the offspring of affected and control parents was employed. The results reveal that there was specificity of expression of anxiety disorders in youth; by contrast, behavior disorders were more strongly associated with parental psychopathology and disrupted home environments in general than with specific parental disorders. Numerous abnormalities in the indirect measures of brain functioning also discriminated between offspring of parents with anxiety disorders and substance abuse, as well as children with attention deficit disorder. These findings are consistent with a congenital/developmental basis for their vulnerability to these conditions. We have continued to analyze this rich data set at the NIMH where we have also made substantial progress in defining the factors involved in the transmission of these conditions in families. These data have provided a valuable resource for trainees in our laboratory who have learned to analyze data on familial aggregation as we await the results of the ongoing studies in our research group. The results of the recent analyses have been used to refine the research questions and methods of the current NIMH family study that we describe below. The following findings have guided the development of our research. First, we found a syndromic association between mania and migraine with specificity of familial transmission (Merikangas et al, under review). Second, we found a strong within person association between migraine and panic disorder, but there was no familial association between these two conditions (Merikangas et al, under review). Third, we found differential rates of familial aggregation among probands recruited from clinical compared to community settings (Low et al, under review). Fourth, we found that there is specificity of familial transmission of panic and social anxiety disorders, and demonstrate that the association between these disorders in probands and relatives is not attributable to comorbid mood, anxiety or substance use disorders. Therefore, despite the high magnitude of co-occurrence of panic disorder and social anxiety, there are distinct etiologic factors underlying each disorder. Fifth, we found that there is a high magnitude of spousal concordance for substance use disorders and in contrast, no concordance for anxiety disorders. Couples were also concordant for the absence of disorders. Concordance for mental disorders is associated with poorer global functioning and persistent illness among probands. The most likely mechanism for spouse concordance is primary assortative mating for the disorder or its correlates. Sixth, we found that the increased frequency of migraine in women in is not attributable to genetic factors; therefore, the increased exposure to non-familial endogenous or exogenous risk factors for migraine that lower the threshold for expression of migraine in women.

本研究采用家庭研究/纵向高危范式相结合的方法，研究了焦虑症和药物滥用的家族性传播。这项研究还调查了躯体障碍与情绪和焦虑障碍之间的共病。主要发现揭示了焦虑症家族聚集性的特殊性，特别是恐慌症和社交恐惧症的亚型。同样，存在药物滥用的家族聚集性，并提示特定药物的特异性。相比之下，尽管没有证据表明尼古丁依赖的垂直传播，但兄弟姐妹之间尼古丁依赖的风险增加了。关于躯体障碍，研究发现，焦虑症总体上与躯体障碍关系最密切，而且有证据表明，偏头痛与焦虑和情绪障碍在家庭中共同传播。 对患有这些疾病的父母的子女进行了一项为期10年的前瞻性研究，以确定父母疾病的早期迹象和表现。在受影响的父母和对照父母的子女中，采用了个人、家庭和社会危险因素的综合评估领域。结果表明，青少年焦虑症的表现具有特殊性；相比之下，行为障碍与父母的心理病理和家庭环境的破坏总体上比与特定的父母障碍有更强的相关性。大脑功能的间接测量中的许多异常也被区分为患有焦虑症和药物滥用的父母的子女，以及患有注意力缺陷障碍的儿童。这些发现与他们易受这些疾病影响的先天/发育基础是一致的。 我们继续在NIMH分析这一丰富的数据集，在确定这些疾病在家庭中传播所涉及的因素方面也取得了实质性进展。这些数据为我们实验室的受训者提供了宝贵的资源，他们已经学会了在我们等待研究组正在进行的研究的结果时分析关于家庭聚集的数据。最近的分析结果被用来提炼我们下面描述的当前NIMH家族研究的研究问题和方法。 以下发现指导了我们研究的发展。首先，我们发现躁狂症和偏头痛之间的症状关联与家族传播的特异性有关(Merikangas等人，在综述中)。其次，我们发现偏头痛和惊恐障碍之间有很强的个人相关性，但这两种疾病之间没有家族相关性(Merikangas等人，正在审查中)。第三，我们发现，与社区环境相比，从临床招募的先证者的家庭聚集率存在差异(Low等人，正在审查中)。第四，我们发现恐慌症和社交焦虑症的家族传播具有特殊性，并证明先证者和亲属之间的联系不是由于共病的情绪、焦虑或物质使用障碍。因此，尽管惊恐障碍和社交焦虑同时出现的几率很高，但每种障碍背后都有不同的病因。第五，我们发现，对于物质使用障碍，配偶之间存在很高程度的一致性，而对于焦虑症，则没有一致性。夫妻之间没有精神障碍也是一致的。精神障碍的一致性与先证者的全球功能较差和持续性疾病有关。配偶和谐的最有可能的机制是对这种障碍或其相关者进行初级分类交配。第六，我们发现女性偏头痛发病率的增加不是由于遗传因素；因此，暴露于非家族性内源性或外源性偏头痛风险因素的增加降低了女性偏头痛的表达门槛。