青少年居住流动性、遗传易感性与精神分裂症、双相情感障碍和重度抑郁症的风险。
Adolescent residential mobility, genetic liability and risk of schizophrenia, bipolar disorder and major depression.
机构信息
National Institute of Mental Health, Maryland, USA.
National Center for Register-Based Research, Business and Social Sciences, Aarhus University; The Lundbeck Foundation Initiative for Integrative Psychiatric Research; and Centre for Integrated Register-Based Research, Aarhus University, Denmark.
出版信息
Br J Psychiatry. 2020 Jul;217(1):390-396. doi: 10.1192/bjp.2020.8.
BACKGROUND
Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear.
AIMS
We used a population-based case-cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10-14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder.
METHOD
Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981-1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses.
RESULTS
PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00-1.16; and odds ratio 1.10, 95% CI 1.04-1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5-11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08-1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92-4.86; three or more moves and bipolar disorder).
CONCLUSIONS
Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.
背景
在成长过程中，尤其是青少年时期，居住流动性与多种负面心理健康结果有关。然而，这些关联是否受到未测量的家庭因素（包括遗传易感性）的混杂影响尚不清楚。
目的
我们使用基于人群的病例-队列研究来评估精神分裂症、双相情感障碍和重度抑郁症的多基因风险评分（PRS）是否与 10-14 岁时的流动性有关，以及 PRS 和父母精神障碍史是否共同解释了流动性与每种疾病之间的关联。
方法
丹麦民事和精神登记处之间链接了病例（n=4207 例精神分裂症，n=1402 例双相情感障碍，n=18215 例重度抑郁症）和一个随机人群样本（n=17582）的信息。全基因组数据来自丹麦新生儿筛查生物库，PRS 是根据单独的大型荟萃分析结果计算得出的。
结果
精神分裂症和重度抑郁症的 PRS 与搬迁一次（优势比 1.07，95%CI 1.00-1.16；和优势比 1.10，95%CI 1.04-1.17）之间存在微弱关联，但两次或三次或更多次搬迁则不然。流动性与每种疾病均呈正相关，搬迁次数越多，风险越高。调整 PRS 会略微降低关联的幅度。同时调整 PRS 和父母精神障碍史会使估计值降低 5-11%。在完全调整的模型中，流动性与所有三种疾病均相关；风险比范围从 1.33（95%CI 1.08-1.62；一次搬迁和双相情感障碍）到 3.05（95%CI 1.92-4.86；三次或更多次搬迁和双相情感障碍）。
结论
流动性与精神分裂症、双相情感障碍和抑郁症的关联似乎并非归因于此处测量的遗传易感性。流动性关联的潜在家族性混杂可能主要是环境性质的。
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