Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
Schizophr Res. 2011 Dec;133(1-3):143-9. doi: 10.1016/j.schres.2011.09.014. Epub 2011 Oct 12.
Large individual variation in the clinical presentation of schizophrenia-spectrum disorders raises key questions regarding their aetiological underpinnings. In this respect, age at onset of the disorder is a particularly interesting marker of liability, as it has been reported to be associated with other signs of developmental compromise, such as male gender, increased presence of familial history of psychosis and poor premorbid adjustment, as well as a more severe clinical outcome in terms of cognition and symptomatology. The association between these variables has encouraged a neurodevelopmental perspective of the aetiological mechanisms involved in the pathophysiology of schizophrenia. However, the complex relationships within neurobiological liability markers, and between these markers and clinical outcome, remain to be understood. In the present study, we used a path-analytic approach to explore: i) the fit of the model to observed data; and both ii) direct and iii) indirect associations between the variables. In a sample of 106 patients with schizophrenia-spectrum disorders, we found a good fit of the model to the observed data, providing further evidence that supports a neurodevelopmental pathway to the disease in a subgroup of patients. However, the most parsimonious model showed complex relationships, where age at onset and premorbid functioning acted as mediators between gender, familial history of psychosis and clinical outcome. These findings refine earlier explanations of the neurobiological basis of schizophrenia, with potential applications in genetic studies based on more homogeneous forms of the disease. We further discuss the putative implications of our results in clinical practice and prevention policies.
精神分裂症谱系障碍的临床表现存在个体差异，这对其病因基础提出了关键问题。在这方面，疾病的发病年龄是一个特别有趣的易感性标志物，因为它与其他发育受损的迹象有关，例如男性性别、家族精神病史的增加和较差的发病前适应能力，以及认知和症状方面更严重的临床结果。这些变量之间的关联促使人们从神经发育的角度来理解精神分裂症病理生理学中涉及的病因机制。然而，神经生物学易感性标志物内部以及这些标志物与临床结果之间的复杂关系仍有待理解。在本研究中，我们使用路径分析方法来探讨：i）该模型与观察数据的拟合程度；以及 ii）这些变量之间的直接和 iii）间接关联。在一个 106 名精神分裂症谱系障碍患者的样本中，我们发现该模型与观察数据的拟合程度良好，这进一步提供了支持疾病在亚组患者中具有神经发育途径的证据。然而，最简约的模型显示出复杂的关系，其中发病年龄和发病前功能在性别、家族精神病史和临床结果之间起中介作用。这些发现细化了早期对精神分裂症神经生物学基础的解释，在基于更同质形式的疾病的遗传研究中具有潜在的应用价值。我们进一步讨论了我们研究结果在临床实践和预防政策中的潜在影响。
