Moser Paul
Centre de Recherche Pierre Fabre 17, Avenue Jean Moulin, 81106 Castres Cédex, France.
Eur Neuropsychopharmacol. 2014 May;24(5):774-87. doi: 10.1016/j.euroneuro.2013.11.004. Epub 2013 Nov 22.
Many lines of evidence suggest that schizophrenia has a major developmental component and that environmental factors that disrupt key stages of development, such as maternal stress during pregnancy as a result of infection or malnutrition, can increase the risk of developing schizophrenia in later life. This review examines how non-clinical neurodevelopmental models pertinent to schizophrenia have been evaluated for their ability to reproduce behavioural deficits related to the negative symptoms of schizophrenia. The more frequently used are the prenatal application of the mitotoxic agent methylazoxymethanol, prenatal immune challenge and the neonatal ventral hippocampus lesion model. In general they have been extensively evaluated in models considered relevant to positive symptoms of schizophrenia. In contrast, very few studies have examined tests related to negative symptoms and, when they have, it has almost exclusively been a social interaction model. Other aspects related to negative symptoms such as anhedonia, affective flattening and avolition have almost never been studied. Further studies examining other components of negative symptomatology are needed to more clearly associate these deficits with a schizophrenia-like profile as social withdrawal is a hallmark of many disorders. Although there are no truly effective treatments for negative symptoms, better characterisation with a broader range of drugs used in schizophrenia will be necessary to better evaluate the utility of these models. In summary, developmental models of schizophrenia have been extensively studied as models of positive symptoms but, given the unmet need in the clinic, the same effort now needs to be made with regard to negative symptoms.
许多证据表明，精神分裂症有一个主要的发育成分，并且破坏发育关键阶段的环境因素，如孕期因感染或营养不良导致的母亲应激，会增加日后患精神分裂症的风险。本综述探讨了与精神分裂症相关的非临床神经发育模型在再现与精神分裂症阴性症状相关的行为缺陷方面的评估情况。使用较为频繁的是线粒体毒素甲基氧化偶氮甲醇的产前应用、产前免疫应激和新生鼠腹侧海马损伤模型。总体而言，它们在与精神分裂症阳性症状相关的模型中得到了广泛评估。相比之下，很少有研究考察与阴性症状相关的测试，即便有研究，几乎也完全是社交互动模型。与阴性症状相关的其他方面，如快感缺失、情感平淡和意志缺乏，几乎从未被研究过。需要进一步研究阴性症状学的其他成分，以便更清楚地将这些缺陷与精神分裂症样特征联系起来，因为社交退缩是许多疾病的一个标志。尽管目前尚无真正有效的阴性症状治疗方法，但需要用更多用于精神分裂症的药物进行更全面的表征，以便更好地评估这些模型的效用。总之，精神分裂症的发育模型作为阳性症状模型已得到广泛研究，但鉴于临床上未满足的需求，现在需要在阴性症状方面做出同样的努力。
