MECHANISMS OF SCHIZOPHRENIA DEVELOPMENT : BRAIN IMAGING, NEUROPSYCHOLOGICAL, AND PSYCHOPHARMACOLOGICAL STUDIES

A.精神分裂症患者的脑成像和神经心理学研究基于Voxe的精神分裂症患者和分裂型障碍患者大脑灰质的形态计量学比较显示，分裂型障碍患者左侧额叶下部、脑岛、颞叶上方和内侧区域的灰质较少。精神分裂症患者双侧额叶内侧、额叶下部、颞叶内侧和隔区，左侧额叶中段、眶前叶、岛叶和颞叶上区灰质减少，左侧基底节灰质增多。这些结果提示，精神分裂症的发展存在着颞叶-额叶两步假说：颞叶的改变可能构成精神分裂症的易感性，额叶的额外改变可能会引发精神病性症状。对前扣带回、海马体、海马旁回、杏仁核、前内囊和额叶的感兴趣区进行体积分析，得到了与这一假说一致的结果。精神分裂症患者和分裂型障碍患者之间的神经心理特征也进行了比较。两组患者都观察到了言语记忆障碍，但精神分裂症患者的注意力和执行功能受损更严重。B.动物模型苯环利定(PGP)或MK-801亚慢性治疗对大鼠社会交往的损害。亚慢性给予PCP显著降低了终纹床核、外侧隔核和外侧下丘脑等几个脑区的V1a受体结合部位的密度，这些部位由[125I]-线性AVP拮抗剂标记。这些结果提示，NMDA拮抗剂对中枢加压素能系统和社会相互作用有调节作用。研究人员考虑了这些发现在精神分裂症中的应用。

a.Brain imaging and neuropsychological studies in patients with schizophreniaVoxe-based morphometric comparisons of brain gray matter between patients with schizophrenia and schizotypal disorder revealed that schizotypal disorder patients had less gray matter in the left inferior frontal, insula, superior temporal, and medial temporal regions. Schizophrenia patients showed gray matter reductions in the bilateral medial frontal, inferior frontal, medial temporal, and septal regions, and the left middle frontal, orbitofrontal, insula, and superior temporal regions, and an increased gray matter in the left basal ganglia. These results suggested the temporo-frontal two-step hypothesis for the development of schizophrenia : the temporal lobe changes may constitute vulnerability to schizophrenia and additional changes in the frontal lobes may elicit psychotic symptoms. Consistent findings with this hypothesis were obtained from volumetric regions of interest analyses in the anterior cingulate cortex, hippocampus, parahippocampal gyrus, amygdala, anterior internal capsule, and frontal lobes. Neuropsychological profiles were also compared between patients with schizophrenia and schizotypal disorder. Verbal memory deficits were observed in both patients groups, but attentional and executive functions were more impaired in patients with schizophrenia. These results also support the temporo-frontal two-step hypothesis.b.Animal modelsSubchronic treatment with phencyclidine(PGP) or MK-801 impaired social interactions in rats. Subchronic PCP administration significantly reduced the density of V1a receptor binding sites, labelled by an [125I]-Linear AVP antagonist, in several brain regions including the bed nucleus of stria terminalis, lateral septum, and lateral hypothalamus. These results suggest that NMDA antagonists have modulatory effects on the central vasopressinergic system and social interaction. Implication of these findings in schizophrenia was considered.