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儿童、青少年和青年期抑郁和焦虑障碍症状的表型和遗传结构。

The phenotypic and genetic structure of depression and anxiety disorder symptoms in childhood, adolescence, and young adulthood.

机构信息

King's College London, MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, London, England.

Department of Psychology, Goldsmiths, University of London, London, England.

出版信息

JAMA Psychiatry. 2014 Aug;71(8):905-16. doi: 10.1001/jamapsychiatry.2014.655.

Abstract

IMPORTANCE

The DSM-5 classifies mood and anxiety disorders as separate conditions. However, some studies in adults find a unidimensional internalizing factor that underpins anxiety and depression, while others support a bidimensional model where symptoms segregate into distress (depression and generalized anxiety) and fear factors (phobia subscales). However, little is known about the phenotypic and genetic structure of internalizing psychopathology in children and adolescents.

OBJECTIVE

To investigate the phenotypic associations between depression and anxiety disorder symptom subscales and to test the genetic structures underlying these symptoms (DSM-5-related, unidimensional and bidimensional) across 3 developmental stages: childhood, adolescence, and early adulthood.

DESIGN, SETTING, AND PARTICIPANTS: Two population-based prospective longitudinal twin/sibling studies conducted in the United Kingdom. The child sample included 578 twins (mean age, approximately 8 and 10 years at waves 1 and 2, respectively). The adolescent and early adulthood sample included 2619 twins/siblings at 3 waves (mean age, 15, 17, and 20 years at each wave).

MAIN OUTCOMES AND MEASURES

Self-report symptoms of depression and anxiety disorders.

RESULTS

Phenotypically, when controlling for other anxiety subscales, depression symptoms were only associated with generalized anxiety disorder symptoms in childhood (r = 0.20-0.21); this association broadened to panic and social phobia symptoms in adolescence (r = 0.17-0.24 and r = 0.14-0.16, respectively) and all anxiety subscales in young adulthood (r = 0.06-0.19). The genetic associations were in line with phenotypic results. In childhood, anxiety subscales were influenced by a single genetic factor that did not contribute to genetic variance in depression symptoms, suggesting largely independent genetic influences on anxiety and depression. In adolescence, genetic influences were significantly shared between depression and all anxiety subscales in agreement with DSM-5 conceptualization. In young adulthood, a genetic internalizing factor influencing depression and all anxiety subscales emerged, alongside a small significant genetic fear factor.

CONCLUSIONS AND RELEVANCE

These results provide preliminary evidence for different phenotypic and genetic structures of internalizing disorder symptoms in childhood, adolescence, and young adulthood, with depression and anxiety becoming more associated from adolescence. The results inform molecular genetics research and transdiagnostic treatment approaches. The findings affirm the need to continue examining the classification of mood and anxiety disorders in diagnostic systems.

摘要

重要性

DSM-5 将心境和焦虑障碍分类为独立的病症。然而,一些针对成年人的研究发现,有一种单一的内在因素可以支撑焦虑和抑郁,而另一些研究则支持一种双维度模型,其中症状分为痛苦(抑郁和广泛性焦虑)和恐惧因素(恐惧症子量表)。然而,对于儿童和青少年内在精神病理学的表型和遗传结构知之甚少。

目的

研究抑郁和焦虑障碍症状子量表之间的表型关联,并测试这些症状的遗传结构(DSM-5 相关、单一维度和双维度),跨越三个发展阶段:儿童期、青春期和成年早期。

设计、设置和参与者:在英国进行的两项基于人群的前瞻性纵向双胞胎/兄弟姐妹研究。儿童样本包括 578 对双胞胎(平均年龄,大约在第 1 波和第 2 波分别为 8 岁和 10 岁)。青少年和成年早期样本包括 2619 对双胞胎/兄弟姐妹,在 3 个波次(平均年龄,分别为 15、17 和 20 岁)进行测量。

主要结果和措施

自我报告的抑郁和焦虑障碍症状。

结果

表型上,在控制其他焦虑子量表后,抑郁症状仅与儿童期的广泛性焦虑障碍症状相关(r=0.20-0.21);这种关联在青春期扩大到惊恐障碍和社交恐惧症症状(r=0.17-0.24 和 r=0.14-0.16),并在成年早期与所有焦虑子量表相关(r=0.06-0.19)。遗传关联与表型结果一致。在儿童期,焦虑子量表受单一遗传因素影响,该因素对抑郁症状的遗传变异没有贡献,表明焦虑和抑郁的遗传影响基本独立。在青春期,遗传影响在抑郁和所有焦虑子量表之间显著共享,与 DSM-5 的概念化一致。在成年早期,出现了一个影响抑郁和所有焦虑子量表的遗传内在因素,同时还有一个较小的显著遗传恐惧因素。

结论和相关性

这些结果为儿童期、青春期和成年早期内在障碍症状的不同表型和遗传结构提供了初步证据,表明抑郁和焦虑从青春期开始变得更为相关。这些结果为分子遗传学研究和跨诊断治疗方法提供了信息。这些发现证实需要继续检查诊断系统中情绪和焦虑障碍的分类。

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