Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia
Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia
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DOI：
10.1038/sj.mp.4000473
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发表时间：
1999-03-01
影响因子：
11
通讯作者：
Lerer, B
中科院分区：
文献类型：
--
作者：
Agid, O;Shapira, B;Lerer, B
目前的重点是确定易患精神疾病的基因，因此更需要确定与遗传易感性相互作用的环境因素，从而导致这些疾病的多因素病因。其中一个因素可能是早期父母丧失（EPL）。在这个世纪的大部分时间里，早期环境压力因素（如失去父母）与成年后的精神病理之间的假定关系一直引起精神病学家的兴趣。我们报告了一项病例对照研究，该研究评估了重度抑郁症（MD）、双相情感障碍（BPD）和精神分裂症（SCZ）患者因父母死亡或17岁前永久分离而发生EPL的比率，并与单独匹配的健康对照受试者（MD- control， 79对；BPD- control， 79对；SCZ- control， 76对）进行了比较。童年失去父母显著增加成年后患锰的可能性（OR = 3.8, P = 0.001）。永久分离造成的损失（P = 0.008）比死亡造成的损失更为显著，9岁之前的损失（OR = 11.0, P = 0.003）与童年后期和青春期相比更为显著。在BPD中EPL的总发生率也增加（OR = 2.6, P = 0.048），但在任何亚类别的损失中没有显著的发现。精神分裂症患者EPL发生率显著升高（OR = 3.8, P = 0.01），尤其在9岁前（OR = 4.3, P = 0.01）。在抽取匹配样本的更大患者组（MD, n = 136； BPD, n = 107； SCZ, n = 160）中，比较有EPL病史和无EPL病史受试者的社会心理、医学和临床特征，没有什么显著发现。然而，在对照组（n = 170）中，经历过EPL的受试者，报告收入较低，离婚频率较高，更有可能独自生活，更有可能吸烟或吸烟，并报告更多的身体疾病（P = 0.03-0.001）。在许多动物物种中，早期环境压力因素（如母性剥夺）的长期神经生物学后果已被广泛研究。最近，下丘脑-垂体-肾上腺轴功能的持续变化，包括促肾上腺皮质激素释放因子的基因表达，受到了特别的关注。类似的过程可能涉及EPL对人类精神病理易感性的影响，通过改变对压力的反应。遗传易感性可能影响个体对早期环境压力影响的易感性程度，也可能决定个体因压力而变得脆弱的精神病理实体。
The current focus on identifying genes which predispose to psychiatric illness sharpens the need to identify environmental factors which interact with genetic predisposition and thus contribute to the multifactorial causation of these disorders. One such factor may be early parental loss (EPL). The putative relationship between early environmental stressors such as parental loss and psychopathology in adult life has intrigued psychiatrists for most of this century. We report a case control study in which rates of EPL, due to parental death or permanent separation before the age of 17 years were evaluated in patients with major depression (MD), bipolar disorder (BPD) and schizophrenia (SCZ), compared to individually matched, healthy control subjects (MD-Control, 79 pairs; BPD-Control, 79 pairs; SCZ-Control, 76 pairs). Loss of parent during childhood significantly increased the likelihood of developing Mn during adult life (OR = 3.8, P = 0.001). The effect of loss due to permanent separation (P = 0.008) was more striking than loss due to death, as was loss before the age of 9 years (OR = 11.0, P = 0.003) compared to later childhood and adolescence. The overall rate of EPL was also increased in BPD (OR = 2.6, P = 0.048) but there were no significant findings in any of the subcategories of loss. A significantly increased rate of EPL was observed in schizophrenia patients (OR = 3.8, P = 0.01), particularly before the age of 9 years (OR = 4.3, P = 0.01). Comparison of psychosociaI, medical and clinical characteristics of subjects with and without a history of EPL, within the larger patient groups from which the matched samples were drawn (MD, n = 136; BPD, n = 107; SCZ, n = 160), yielded few significant findings. Among the controls (n = 170), however, subjects who had experienced EPL, reported lower incomes, had been divorced more frequently, were more likely to be living alone, were more likely to smoke or have smoked cigarettes and reported more physical illness (P = 0.03-0.001). Long term neurobiological consequences of early environmental stressors such as maternal deprivation have been extensively studied in many animal species. Recently, enduring changes in hypothalamic-pituitary-adrenal axis function, including corticotrophin releasing factor gene expression, have received particular attention. Analogous processes may be implicated in the effect of EPL on human vulnerability to psychopathology, via alterations in responsiveness to stress. Genetic predisposition may influence the degree of susceptibility of the individual to the effects of early environmental stress and may also determine the psychopathological entity to which the individual is rendered vulnerable as a consequence of the stress.