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.

这项研究通过家庭研究/纵向高风险范式的结合检查了焦虑症和药物滥用的家族传播。这项研究还研究了身体障碍，情绪和焦虑症之间的合并症。主要发现揭示了焦虑症的家族性疾病的特异性，尤其是恐慌和社会恐惧症亚型。同样，存在滥用药物的家族性聚集，并提出了特定药物的特异性。相反，尽管没有证据表明尼古丁依赖性的垂直传播，但兄弟姐妹之间尼古丁依赖性的风险增加了。关于身体障碍，发现焦虑症通常与身体障碍最密切相关，并且有证据表明偏头痛与家庭中的焦虑和情绪障碍共同传播。 为了确定父母疾病的早期体征和表现，对父母的后代进行了10年的前瞻性研究。在受影响和控制父母的后代中对个人，家庭和社会风险因素的评估的全面领域。结果表明，年轻人表达焦虑症的特异性。相比之下，与特定的父母疾病相比，行为障碍与父母的心理病理学和一般家庭环境的干扰更加密切。间接措施的大脑功能措施的许多异常也歧视了焦虑症和药物滥用父母的后代，以及患有注意力缺陷障碍的儿童。这些发现与先天性/发展基础一致，以使其易受这些条件的脆弱性。 我们继续在NIMH上分析这种丰富的数据集，我们在定义家庭中传播这些条件的因素方面也取得了重大进展。这些数据为我们实验室的受训者提供了宝贵的资源，他们在等待研究小组正在进行的研究结果时学会了分析家庭聚集数据。最近的分析结果已用于完善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的研究的发展。首先，我们发现躁狂症与偏头痛之间的综合症与家族传播的特异性（Merikangas等人，正在综述中）。其次，我们发现偏头痛与恐慌症之间的人内部有很强的联系，但是这两个条件之间没有家族关联（Merikangas等人，正在审查中）。第三，我们发现与社区环境相比，从临床招募的概率中的家族聚集率差异（Low等人，正在审查中）。第四，我们发现恐慌和社交焦虑症的家族传播特异性，并证明这些疾病与亲戚中的这些疾病之间的关联并不归因于合并症的情绪，焦虑或药物使用障碍。因此，尽管恐慌症和社交焦虑的同时存在很高，但每种疾病的基础存在明显的病因学因素。第五，我们发现物质使用障碍的配偶一致性很高，相反，焦虑症没有一致性。夫妻也与缺乏疾病有关。精神障碍的一致性与概率之间的全球功能较差和持续性疾病有关。配偶一致性的最可能的机制是该疾病或其相关性的主要分类交配。第六，我们发现女性中偏头痛的频率增加并非归因于遗传因素。因此，偏头痛的非家族内源性或外源性危险因素的暴露增加降低了妇女偏头痛的阈值。