FETAL ORIGIN OF ADULT DISEASE? A POPULATION-BASED STUDY OF THE OFFSPRING OF WOMEN WITH SEVERE MENTAL DISORDERS

成人疾病的胎儿起源是目前对常见疾病（缺血性心脏病、高血压、糖尿病）和行为问题（自杀、犯罪）进行流行病学研究的一个有影响力的范例。它假定一个早期的病理生理规划的结果，成为明显的成年生活。在拟议的研究中，我们的目的是通过对1980-2001年出生于西澳大利亚州的所有儿童（N-5150）的发育结局、前因和伴随的风险因素以及神经精神病发病率谱进行基于人群的研究，与儿童相比，（N-504，553）出生的妇女没有诊断出精神疾病。这项研究将以记录联系为基础，利用西澳大利亚州多个综合人口数据库的独特资源。具体来说，本研究将确定四个连续出生队列的发育结果和发病率的范围（1980-84年; 1985-89年; 1990-94年; 1995-2001年）研究了高遗传和环境风险儿童的健康状况，并研究了其与特定风险因素的关系，包括家族遗传负荷、产科并发症、孕产妇疾病的严重程度和心理社会逆境。这项研究将是同类研究中的第一项，其结果将为主要精神障碍的病因学研究以及临床和公共卫生实践提供信息。它将提供关于基本问题的新数据，例如精神分裂症病因中遗传风险和环境因素之间的相互作用，以及发展严重精神疾病的风险在多大程度上不可改变地嵌入其胎儿起源，或可通过随后的缓解因素和适当干预加以改变。

Fetal origin of adult disease is a currently influential paradigm in epidemiological research into common diseases (ischaemic heart disease, hypertension, diabetes) and behaviour problems (suicide, criminal offending). It postulates an early pathophysiological programming of outcomes that become manifest in adult life. In the proposed research we aim to examine key aspects of this model by conducting a population-based study on the developmental outcomes, antecedent and concomitant risk factors, and a spectrum of neuropsychiatric morbidity in all children (N-5150) born in Western Australia in 1980-2001 to women diagnosed with schizophrenia, bipolar affective disorder or unipolar depression, as compared to children (N-504,553) born to women without a diagnosed psychiatric illness. The study will be based on record linkage, utilising the unique resource of multiple, comprehensive population databases in Western Australia. Specifically, this research will identify the range of developmental outcomes and morbidity in four consecutive birth cohorts (1980-84; 1985-89; 1990-94; and 1995-2001) of children at high genetic and environmental risk and examine their relationship to specific risk factors, including familial genetic load, obstetric complications, severity of maternal illness, and psychosocial adversity. The study will be the first of its kind and its findings will inform aetiological research into the major mental disorders, as well as clinical and public health practice. It will provide novel data on fundamental issues, such as the interaction between genetic risk and environmental factors in the causation of schizophrenia, as well as on the extent to which the risk of developing severe mental illness is immutably embedded in its fetal origin, or is modifiable by subsequent mitigating factors and appropriate intervention.