Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
School of medical sciences, Örebro University, Örebro, Sweden.
Transl Psychiatry. 2023 Aug 14;13(1):282. doi: 10.1038/s41398-023-02571-7.
Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53-1.58] to 2.65 [ ≥ 4 adversities; 1.98-3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59-1.84] to 1.37 [1.30-1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.
早年累积暴露于心理社会逆境已被证明是注意力缺陷多动障碍（ADHD）和自闭症的风险因素，且这两种疾病常同时发生。然而，目前尚不清楚这种关联是否反映了因果效应或家族性混杂。我们旨在评估家庭中累积的心理社会逆境是否会增加后代患 ADHD 和自闭症的风险，同时考虑到未测量的家族性混杂。我们使用了瑞典 1990 年至 2009 年间出生的 1877901 名个体的基于人群的队列。参与者从 3 岁开始随访至 2013 年，中位随访时间为 13.8 年。我们基于 7 个心理社会逆境因素创建了一个累积指数。我们使用 Cox 回归来估计与神经发育状况相关的累积心理社会逆境的风险比（HR）。为了解决家族性混杂，我们在不同亲缘关系的亲属群体中（兄弟姐妹和同父异母/同母异父兄弟姐妹以及表兄弟姐妹）重复了这些分析。在一般人群中，观察到累积暴露于心理社会逆境与 ADHD 之间存在剂量-反应关系（调整协变量的 HR（95%置信区间范围为 1.55[1 种逆境；1.53-1.58]至 2.65[≥4 种逆境；1.98-3.54]）。对于自闭症，未观察到明确的剂量-反应关系（HR 范围为 1.04[0.59-1.84]至 1.37[1.30-1.45]）。在亲属分析中，随着亲缘关系水平的增加，ADHD 和自闭症的 HR 降低。在一般人群中，累积暴露于心理社会逆境与 ADHD 和自闭症均相关，这些关联部分可由亲属之间未测量的家族性混杂解释。这突显了在心理社会逆境与 ADHD 和自闭症研究中使用基于家庭的设计的必要性。
