Characterizing Developmental Trajectories and the Role of Neuropsychiatric Genetic Risk Variants in Early-Onset Depression.
Characterizing Developmental Trajectories and the Role of Neuropsychiatric Genetic Risk Variants in Early-Onset Depression.
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DOI：
10.1001/jamapsychiatry.2018.3338
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发表时间：
2019-03-01
期刊：
影响因子：
25.8
通讯作者：
Thapar A
中科院分区：
文献类型：
--
作者：
Rice F;Riglin L;Thapar AK;Heron J;Anney R;O'Donovan MC;Thapar A
神经精神疾病遗传风险变异是否影响青年抑郁症的发展轨迹？在这项以人群为基础的研究中，包括7543名青少年，确定了不同的抑郁轨迹类。青春期后发病组（17.3%的样本）表现出典型的抑郁轨迹，并与重度抑郁症风险等位基因相关，青春期早期发病组（9.0%）在12岁时表现出临床显著症状，并与精神分裂症和注意缺陷多动障碍遗传风险、儿童期注意缺陷多动障碍和神经发育特征相关。青年抑郁症是异质性的，研究结果与新出现的证据相一致，即神经发育成分对某些抑郁症的影响，而且这一成分在发病很早的时候更有可能发生。抑郁症通常首先在青春期表现出来。此后，个体的轨迹变化很大，但不知道是什么塑造了青年抑郁症的轨迹。成人研究表明，精神分裂症（一种具有神经发育成分的精神疾病）的遗传风险可能导致抑郁症的早期发作。检验以下假设：抑郁症状有不同的轨迹，神经发育性精神障碍（例如，精神分裂症、注意缺陷/多动障碍[ADHD]）以及重度抑郁症（MDD）的遗传易感性有助于早发性抑郁。雅芳家长和儿童纵向研究是一项持续的、前瞻性的、纵向的、以人群为基础的队列研究，自1990年9月6日以来一直在收集数据，包括7543名在多个时间点有抑郁症状的青少年的数据。本研究于2017年11月10日至2018年8月14日进行。根据自我报告的抑郁症状的临床临界点二分的轨迹; MDD，精神分裂症和ADHD多基因风险评分（PRS）是预测因子。在7543名患有抑郁症的青少年中，平均（SD）年龄为10.64岁，（0.25）年和18.65年（0.49）岁（3568例[47.3%]男性; 3975例[52.7%]女性），确定了3种轨迹类别：持续性低（73.7%），青春期后期发病（17.3%）和青春期早期发病（9.0%）。青春期晚发型仅与MDD遗传风险相关（MDD PRS：比值比[OR]，1.27; 95%CI，1.09-1.48; P = .003）。青春期早期发病类型也与MDD遗传风险相关（MDD PRS：OR，1.24; 95% CI，1.06-1.46; P = .007），但另外存在神经发育障碍的遗传风险（精神分裂症PRS：OR，1.22; 95%CI，1.04-1.43; P = .01; ADHD PRS：OR，1.32; 95%CI，1.13-1.54; P < .001）和儿童ADHD（χ21 = 6.837; P = 0.009）和神经发育特征（语用语言困难：OR，1.31; P = 0.004;社交困难：OR，0.68; P <0.001）。这项研究的结果似乎证明了明显的抑郁轨迹的证据，主要是由发病年龄区分。在16岁时出现临床显著症状的更典型的抑郁轨迹与MDD遗传风险相关。不太常见的抑郁轨迹，发病很早，特别与ADHD和精神分裂症的遗传风险有关，并且在表型上与儿童ADHD和神经发育特征有关。研究结果与新出现的证据一致，在某些情况下，抑郁症的神经发育组件，并建议，该组件的存在可能更有可能时，抑郁症的发病是非常早的。这项基于人群的研究探讨了神经精神疾病的遗传风险变异与儿童抑郁症发病年龄和轨迹之间的关系。
Do neuropsychiatric disorder genetic risk variants influence developmental trajectories of depression in youth? In this population-based study including 7543 adolescents, distinct depression trajectory classes were identified. A later-adolescence–onset class (17.3% of the sample) showed a typical depression trajectory and was associated with major depressive disorder risk alleles, and an early-adolescence–onset class (9.0%) showed clinically significant symptoms at age 12 years and was associated with schizophrenia and attention-deficit hyperactivity disorder genetic risk, childhood attention-deficit hyperactivity disorder, and neurodevelopmental traits. Depression in youth is heterogeneous; findings are consistent with emerging evidence for a neurodevelopmental component to some cases of depression and that this component is more likely when onset is very early. Depression often first manifests in adolescence. Thereafter, individual trajectories vary substantially, but it is not known what shapes depression trajectories in youth. Adult studies suggest that genetic risk for schizophrenia, a psychiatric disorder with a neurodevelopmental component, may contribute to an earlier onset of depression. To test the hypothesis that there are distinct trajectories of depressive symptoms and that genetic liability for neurodevelopmental psychiatric disorders (eg, schizophrenia, attention deficit/hyperactivity disorder [ADHD]), as well as for major depressive disorder (MDD), contribute to early-onset depression. The Avon Longitudinal Study of Parents and Children is an ongoing, prospective, longitudinal, population-based cohort that has been collecting data since September 6, 1990, including data on 7543 adolescents with depressive symptoms at multiple time points. The present study was conducted between November 10, 2017, and August 14, 2018. Trajectories based on self-reported depressive symptoms dichotomized by the clinical cutpoint; MDD, schizophrenia, and ADHD polygenic risk score (PRS) were predictors. In 7543 adolescents with depression data on more than 1 assessment point between a mean (SD) age of 10.64 (0.25) years and 18.65 (0.49) years (3568 [47.3%] male; 3975 [52.7%] female), 3 trajectory classes were identified: persistently low (73.7%), later-adolescence onset (17.3%), and early-adolescence onset (9.0%). The later-adolescence–onset class was associated with MDD genetic risk only (MDD PRS: odds ratio [OR], 1.27; 95% CI, 1.09-1.48; P = .003). The early-adolescence–onset class was also associated with MDD genetic risk (MDD PRS: OR, 1.24; 95% CI, 1.06-1.46; P = .007) but additionally with genetic risk for neurodevelopmental disorders (schizophrenia PRS: OR, 1.22; 95% CI, 1.04-1.43; P = .01; ADHD PRS: OR, 1.32; 95% CI, 1.13-1.54; P < .001) and childhood ADHD (χ21 = 6.837; P = .009) and neurodevelopmental traits (pragmatic language difficulties: OR, 1.31; P = .004; social communication difficulties: OR, 0.68; P < .001). The findings of this study appear to demonstrate evidence of distinct depressive trajectories, primarily distinguished by age at onset. The more typical depression trajectory with onset of clinically significant symptoms at age 16 years was associated with MDD genetic risk. The less-common depression trajectory, with a very early onset, was particularly associated with ADHD and schizophrenia genetic risk and, phenotypically, with childhood ADHD and neurodevelopmental traits. Findings are consistent with emerging evidence for a neurodevelopmental component in some cases of depression and suggest that the presence of this component may be more likely when the onset of depression is very early. This population-based study examines the association between genetic risk variants for neuropsychiatric disorders and the age at onset and trajectories of depression in children.
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影响因子：
--
作者：
Jaffee, SR;Moffitt, TE;Martin, J
通讯作者：
Martin, J
影响因子：
3.3
作者：
Harrington, R;Rutter, M;Fombonne, E
通讯作者：
Fombonne, E
影响因子：
120.7
作者：
JOHNSON, J;WEISSMAN, MM;KLERMAN, GL
通讯作者：
KLERMAN, GL
影响因子：
6.1
作者：
Fraser A;Cooper M;Agha SS;Collishaw S;Rice F;Thapar A;Eyre O
通讯作者：
Eyre O
DOI：
10.1192/bjp.bp.109.073429
发表时间：
2010-02
期刊：
The British journal of psychiatry : the journal of mental science
影响因子：
--
作者：
Craddock N;Owen MJ
通讯作者：
Owen MJ