Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
Psychol Med. 2019 Nov;49(15):2582-2590. doi: 10.1017/S0033291718003550. Epub 2018 Nov 28.
Studies on the stability of genetic risk for depression have relied on self-reported symptoms rather than diagnoses and/or short follow-up time. Our aim is to determine to what degree genetic and environmental influences on clinically assessed major depressive disorder (MDD) are stable between age 18 and 45.
A population-based sample of 11 727 twins (6875 women) born between 1967 and 1991 was followed from 2006 to 2015 in health registry data from primary care that included diagnoses provided by treating physicians. Individuals with schizophrenia or bipolar disorder (n = 163) were excluded. We modelled genetic and environmental risk factors for MDD in an accelerated longitudinal design.
The best-fitting model indicated that genetic influences on MDD were completely stable from ages 18 to 45 and explained 38% of the variance. At each age, the environmental risk of MDD was determined by the risk at the preceding observation, plus new environmental risk, with an environmental correlation of +0.60 over 2 years. The model indicated no effects of shared environment and no environmental effects stable throughout the observational period. All long-term stability was therefore explained by genetic factors.
Different processes unfolded in the genetic and environmental risk for MDD. The genetic component is stable from later adolescence to middle adulthood and accounted for nearly all long-term stability. Therefore, molecular genetic studies can use age-heterogenous samples when investigating genetic risk variants of MDD. Environmental risk factors were stable over a short span of years with associations rapidly decreasing and no evidence of permanent environmental scarring.
研究抑郁遗传风险的稳定性依赖于自我报告的症状,而不是诊断和/或随访时间短。我们的目的是确定遗传和环境因素对临床评估的重度抑郁症(MDD)的影响在 18 岁至 45 岁之间的稳定程度。
对出生于 1967 年至 1991 年的 11727 对双胞胎(6875 名女性)进行了一项基于人群的研究,从 2006 年到 2015 年,通过初级保健的健康登记数据进行随访,其中包括主治医生提供的诊断。排除患有精神分裂症或双相情感障碍的个体(n=163)。我们采用加速纵向设计对 MDD 的遗传和环境风险因素进行建模。
最佳拟合模型表明,MDD 的遗传影响从 18 岁到 45 岁完全稳定,解释了 38%的方差。在每个年龄,MDD 的环境风险由前一次观察的风险加上新的环境风险决定,2 年内的环境相关性为+0.60。该模型表明不存在共同环境的影响,也不存在整个观察期间稳定的环境影响。因此,所有的长期稳定性都可以由遗传因素来解释。
不同的过程在 MDD 的遗传和环境风险中展开。遗传因素从青春期后期到成年中期稳定,解释了近所有的长期稳定性。因此,分子遗传学研究在调查 MDD 的遗传风险变异时,可以使用年龄异质的样本。环境风险因素在短时间内稳定,关联迅速下降,没有证据表明存在永久性的环境损伤。