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精神分裂症患者和典型障碍患者脑灰质的基于Voxe的形态计量学比较显示，典型障碍患者在左下额叶、颞叶、上级颞叶和内侧颞叶区域的灰质较少。精神分裂症患者在双侧内侧额叶、下额叶、内侧颞叶和隔区，以及左侧中额叶、眶额、颞叶和上级颞区显示灰质减少，左侧基底节灰质增加。这些结果表明，颞额叶两步假说的发展精神分裂症：颞叶的变化可能构成精神分裂症的脆弱性和额外的变化，额叶可能会引起精神病性症状。与这一假设一致的结果，从体积感兴趣的区域分析前扣带皮层，海马，海马旁回，杏仁核，前内囊，额叶。精神分裂症患者和典型障碍患者的神经心理学特征也进行了比较。两组患者均出现言语记忆障碍，但精神分裂症患者的注意力和执行功能受损更严重。这些结果也支持颞-额两步假说。B.动物模型用苯环利定（PGP）或MK-801亚慢性治疗损害了大鼠的社会互动。亚慢性PCP管理显着降低密度的V1 a受体结合位点，标记的[125 I]-线性AVP拮抗剂，在几个大脑区域，包括床核的终纹，外侧隔，外侧下丘脑。这些结果表明，NMDA受体拮抗剂对中枢加压素系统和社会互动具有调节作用。这些发现在精神分裂症的影响被认为是。

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.