Olié Jean-Pierre, Krebs Marie-Odile, Lôo Henri
SHU/ E0117 INSERM, Hôpital Ste Anne- Université Paris V, 1 rue Cabanis, 75674 Paris 14.
Bull Acad Natl Med. 2005 May;189(5):935-44; discussion 944-7.
Brain anomalies associated with schizophrenic disorders may be of a cognitive, neurophysiological or neurological nature [the latter being relatively minor and nonspecific]. Brain imaging has revealed early anomalies such as cortical-subcortical atrophy and abnormal gyration. These anomalies can also be present in relatives free of schizophrenic symptoms. This raises the question of what determines the transition from vulnerability to clinical onset. There is now evidence that schizophrenic disorders are true brain diseases. This is based on neuropathological studies, brain imaging and clinical findings such as "soft" neurological signs (pyramidal and extrapyramidal symptoms, coordination difficulties, etc.). Cognitive dysfunctions such as attention and memory disorders and abnormal verbal fluency have also been described. Oculomotor pursuit and auditive evoked potentials have identified specific neurophysiological disorders such as N300 and P50 wave modifications. Schizophrenic disorders can also be associated with neuronal abnormalities, notably affecting factors involved in synaptic transmission and plasticity. For example, BDNF protein deficit is linked to certain late-onset forms of schizophrenia. Genetic studies are no longer focusing on a possible disease genotype but rather on phenotypic characteristics determined by simpler genotypes (P50 wave modulation, COMT and BDNF genes). The ultimate objective is to identify high-risk subjects, in order to shorten the treatment delay and thereby improve long-term outcome. The benefit of primary prophylaxis remains to be determined, however.
与精神分裂症相关的脑部异常可能具有认知、神经生理或神经学性质[后者相对轻微且不具特异性]。脑成像已揭示出早期异常,如皮质-皮质下萎缩和异常脑回形成。这些异常在没有精神分裂症症状的亲属中也可能存在。这就提出了一个问题:是什么决定了从易感性到临床发病的转变。现在有证据表明,精神分裂症是真正的脑部疾病。这是基于神经病理学研究、脑成像以及诸如“软性”神经体征(锥体束和锥体外系症状、协调困难等)等临床发现。还描述了诸如注意力和记忆障碍以及言语流畅性异常等认知功能障碍。眼动追踪和听觉诱发电位已确定了特定的神经生理紊乱,如N300和P50波改变。精神分裂症还可能与神经元异常有关,特别是影响参与突触传递和可塑性的因素。例如,脑源性神经营养因子(BDNF)蛋白缺乏与某些迟发性精神分裂症形式有关。基因研究不再关注可能的疾病基因型,而是关注由更简单基因型(P50波调制、儿茶酚-O-甲基转移酶(COMT)和BDNF基因)决定的表型特征。最终目标是识别高危个体,以缩短治疗延迟,从而改善长期预后。然而,一级预防的益处仍有待确定。