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.

本研究结合家庭研究/纵向高风险范式，研究了焦虑症和药物滥用的家族传播。这项研究还调查了身体疾病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的特殊性，特别是恐慌症和社交恐惧症亚型。同样，药物滥用也存在家族聚集性，并暗示了特定药物的特异性。相比之下，虽然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。关于身体疾病，研究发现焦虑症与一般身体疾病的相关性最强，并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后代进行了一项为期 10 年的前瞻性研究，以确定父母疾病的早期体征和表现。对受影响父母和对照父母的后代的个人、家庭和社会风险因素进行了全面的评估。结果表明青少年焦虑症的表现具有特异性；相比之下，与特定的父母疾病相比，行为障碍与父母的精神病理学和家庭环境破坏的关系更密切。大脑功能间接测量中的许多异常也区分了患有焦虑症和药物滥用的父母的后代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/发育基础一致。 我们继续分析 NIMH 的丰富数据集，在确定这些疾病在家庭中传播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学员提供了宝贵的资源，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族聚集数据。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研究的发展。首先，我们发现躁狂症和偏头痛之间存在综合症关联，并且具有家族传播的特异性（Merikangas 等人，正在审查中）。其次，我们发现偏头痛和恐慌症之间存在很强的人际关联，但这两种情况之间没有家族关联（Merikangas 等人，正在审查中）。第三，我们发现从临床招募的先证者与社区环境中招募的先证者之间的家族聚集率存在差异（Low等人，正在审查中）。第四，我们发现惊恐症和社交焦虑症的家族传播具有特异性，并证明先证者和亲属中这些疾病之间的关联并不归因于共病情绪、焦虑或物质使用障碍。因此，尽管惊恐障碍和社交焦虑同时发生的程度很高，但每种疾病都有不同的病因因素。第五，我们发现配偶在物质使用障碍方面具有很高的一致性，而相比之下，在焦虑症方面则没有一致性。夫妻间也没有出现任何障碍。精神障碍的一致性与先证者整体功能较差和持续患病有关。配偶一致性最可能的机制是针对疾病或其相关疾病的主要选型交配。第六，我们发现2017年女性偏头痛发病率的增加与遗传因素无关；因此，接触非家族性内源性或外源性偏头痛危险因素的增加会降低女性偏头痛的表达阈值。