Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University Jena, Jena, Germany.
Neuroimage. 2010 Oct 1;52(4):1314-27. doi: 10.1016/j.neuroimage.2010.05.009. Epub 2010 May 18.
Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodelling/repairing cytosolic phospholipase A(2) (PLA(2)) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-naïve or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA(2)-activity. PLA(2) activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/PLA(2)-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA(2)-activity: in first-episode patients (n=13), PLA(2)-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n=11) showed a wide-spread pattern of associations between PLA(2)-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA(2)-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent-episode patients might point to less specific neurodegenerative aspects of disease progression.
区域性结构脑变化是精神分裂症中最显著的生物学发现之一，但潜在的病理生理变化仍知之甚少。最近的证据表明，异常的神经元/树突状可塑性与膜脂质的改变有关。我们研究了膜脂质重塑/修复胞质型磷脂酶 A2（cytosolic phospholipase A2，PLA2）的血清活性是否与磁共振成像（magnetic resonance images，MRI）中的区域性脑结构有关。该研究纳入了 24 名精神分裂症患者，其中包括未经药物治疗或已停用抗精神病药物的患者，以及 25 名健康对照者。我们使用基于体素的形态测量学（voxel-based morphometry，VBM）分析 T1 高分辨率 MRI 图像，将灰质和白质变化与血清 PLA2 活性相关联。结果显示，患者的 PLA2 活性增加，这与先前的发现一致。与对照组相比，患者的 VBM 组比较显示出额叶和内侧颞叶/海马以及首发患者左侧中/上颞叶的异常。VBM/PLA2 相关性的组间比较显示，在首发患者（n=13）中，PLA2 活性与左前额叶和双侧丘脑的灰质/白质变化之间存在明显的疾病相关相互作用模式。复发性患者（n=11）显示 PLA2 活性与左侧（右侧较少）前额叶和下顶叶皮质、左侧（右侧较少）丘脑和尾状核、左侧内侧颞叶和眶额皮质以及前扣带和小脑之间的结构变化之间存在广泛的关联模式。我们的研究结果表明，在精神分裂症中，膜脂生物化学与局部脑结构异常之间存在潜在的关联。首发患者与慢性患者之间的差异模式可能与疾病发病时 PLA2 增加有关，反映了局部再生活动，而复发患者的相关性可能指向疾病进展的非特异性神经退行性方面。
