Department of Psychiatry,Yale University School of Medicine,New Haven, CT,USA.
Department of Epidemiology,Netherlands Institute of Mental Health and Addiction,Utrecht,The Netherlands.
Psychol Med. 2019 Aug;49(11):1879-1889. doi: 10.1017/S0033291718002635. Epub 2018 Oct 4.
Evidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming 'complicated' by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms.
Data were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was 'complicated' by low-grade psychotic experiences ('attenuated psychosis' - moderately severe) and, overt psychotic symptoms leading to help-seeking ('clinical psychosis' - most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history × environmental risk interaction.
In proxy gene-environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation.
Known environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here.
有证据表明，大麻使用、儿童期逆境和城市化，与遗传风险的替代指标相互作用，可能会促进精神病的发作，即早期情感失调首先变得“复杂”，先是出现轻度精神病，最终出现全面的精神病症状。
数据来自第二次荷兰精神健康调查和发病率研究（NEMESIS-2）的三个波次。环境风险因素（大麻使用、儿童期逆境和城市化）的影响是通过情感失调变得“复杂”的严重程度来分析的，这种严重程度是由低度精神病经历（“轻度精神病”——中度严重）和导致寻求帮助的明显精神病症状（“临床精神病”——最严重）来定义的。根据（主要是）情感障碍的家族史，将家族史和非家族史分层，并将其用作模型中遗传风险与环境风险相互作用的替代指标。
在代理基因-环境相互作用分析中，如果存在家族性情感易感性的证据，儿童期逆境和大麻使用，以及在较小程度上城市化，会显示出比相加风险更大的风险。此外，情感失调的精神病混合严重程度越高（无、轻度精神病、临床精神病），相互作用对比率也会逐渐增加。
已知的环境风险与家族性情感易感性证据相互作用，在一般人群中驱动早期情感失调状态的精神病混合水平，构成了精神病的情感途径。人们对将情感易感性的家族史分解为潜在相互作用的环境和遗传成分很感兴趣，正如这里所示。
