Häfner H, Maurer K, Löffler W, an der Heiden W, Munk-Jørgensen P, Hambrecht M, Riecher-Rössler A
Central Institute of Mental Health, Mannheim, Germany.
Soc Psychiatry Psychiatr Epidemiol. 1998 Aug;33(8):380-6. doi: 10.1007/s001270050069.
The ABC Schizophrenia Study, a large-scale epidemiological and neurobiological research project commenced in 1987, initially pursued two aims: (1) to elucidate the possible causes of the sex difference in age at first admission for schizophrenia and (2) to analyse the early course of the disorder from onset until first contact and its implications for further course and outcome. First, transnational case-register data (for Denmark and Germany) were compared, second, a population-based sample of first-episode cases of schizophrenia (n = 232) were selected and third, the results obtained were compared with data from the WHO Determinants of Outcome Study by using a systematic methodology. A consistent result was a 3-4 years higher age of onset for women by any definition of onset, which was not explainable by social variables, such as differences in the male-female societal roles. A sensitivity-reducing effect of oestrogen on central D2 receptors was identified as the underlying neurobiological mechanism in animal experiments. Applicability to humans with schizophrenia was established in a controlled clinical study. A comparison of familial and sporadic cases showed that in cases with a high genetic load, the sex difference in age of onset disappeared due to a clearly reduced age of onset in women, whereas in sporadic cases it increased. To analyse early course retrospectively, a semistructured interview, IRAOS, was developed. The early stages of the disorder were reconstructed in comparison with age- and sex-matched controls from the same population of origin. The initial signs consisted mainly of negative and affective symptoms, which accumulated exponentially until the first episode, as did the later emerging positive symptoms. Social disability appeared 2-4 years before first admission on average. In early-onset cases, social course and outcome, studied prospectively over 5 years, was determined by the level of social development at onset through social stagnation. In late-onset cases, decline from initially high social statuses occurred. Socially negative illness behaviour contributed to the poor social outcome of young men. Symptomatology and other proxy variables of the disorder showed stable courses and no sex differences. Further aspects tested were the sequence of onset and the influence of substance abuse on the course of schizophrenia, primary and secondary negative symptoms, structural models and symptom clusters from onset until 5 years after first admission.
ABC精神分裂症研究是一项始于1987年的大规模流行病学和神经生物学研究项目，最初有两个目标：（1）阐明精神分裂症首次入院年龄性别差异的可能原因；（2）分析该疾病从发病到首次就诊的早期病程及其对后续病程和结局的影响。首先，比较了跨国病例登记数据（丹麦和德国的），其次，选取了基于人群的精神分裂症首发病例样本（n = 232），第三，使用系统方法将所得结果与世界卫生组织结局决定因素研究的数据进行比较。一个一致的结果是，无论采用何种发病定义，女性的发病年龄都要高3至4岁，这无法用社会变量来解释，比如男女社会角色的差异。在动物实验中，雌激素对中枢D2受体的敏感性降低作用被确定为潜在的神经生物学机制。在一项对照临床研究中确定了其对精神分裂症患者的适用性。家族性病例和散发性病例的比较表明，在遗传负荷高的病例中，发病年龄的性别差异消失，因为女性的发病年龄明显降低，而在散发性病例中这种差异则增大。为了回顾性分析早期病程，开发了一种半结构化访谈，即IRAOS。与来自同一原籍人群、年龄和性别匹配的对照组相比，重建了该疾病的早期阶段。最初的症状主要包括阴性和情感症状，这些症状呈指数级累积直至首次发作，后来出现的阳性症状也是如此。社会残疾平均在首次入院前2至4年出现。在早发病例中，通过社会停滞，发病时的社会发展水平前瞻性地决定了5年的社会病程和结局。在晚发病例中，最初较高的社会地位出现了下降。社会负面的疾病行为导致年轻男性的社会结局不佳。该疾病的症状学和其他替代变量显示出稳定的病程且无性别差异。测试的其他方面包括发病顺序以及药物滥用对精神分裂症病程的影响、原发性和继发性阴性症状、从发病到首次入院后5年的结构模型和症状簇。
