Centre for Neuropsychiatric Schizophrenia Research, CNSR, Psychiatric Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
Int J Neuropsychopharmacol. 2011 Feb;14(1):69-82. doi: 10.1017/S1461145710000817. Epub 2010 Aug 12.
First-generation antipsychotics have been associated with striatal volume increases. The effects of second-generation antipsychotics (SGAs) on the striatum are unclear. Moreover, SGAs may have neuroprotective effects on the hippocampus. Dose-dependent volumetric effects of individual SGAs have scarcely been investigated. Here we investigated structural brain changes in antipsychotic-naive, first-episode schizophrenia patients after 6 months treatment with the SGA, quetiapine. We have recently reported on baseline volume reductions in the caudate nucleus and hippocampus. Baseline and follow-up T1-weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations with psychopathology were assessed. Patients had significant bilateral striatal and hippocampal loss over the 6-month treatment period. When compared to controls the striatal volume loss was most pronounced with low quetiapine doses and less apparent with high doses. Post-hoc analyses revealed that the striatal volume loss was most pronounced in the caudate and putamen, but not in accumbens. Conversely, hippocampal volume loss appeared more pronounced with high quetiapine doses than with low doses. Clinically, higher baseline positive symptoms were associated with more striatal and hippocampal loss over time. Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement of negative symptoms. Progressive regional volume loss in quetiapine-treated, first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying progressive brain changes, specific antipsychotic compounds and clinical symptoms warrant further research.
第一代抗精神病药物与纹状体体积增加有关。第二代抗精神病药物（SGAs）对纹状体的影响尚不清楚。此外，SGAs 可能对海马体具有神经保护作用。个别 SGA 的剂量依赖性体积效应几乎没有被研究过。在这里，我们研究了抗精神病药物初发的首发精神分裂症患者在接受 SGA 喹硫平治疗 6 个月后的大脑结构变化。我们最近报告了尾状核和海马体的基线体积减少。使用基于张量的形态测量法分析了 22 名患者和 28 名匹配的健康对照者的基线和随访 T1 加权图像（3T）。进行了非参数体素-wise 组比较。对纹状体、海马体和脑室进行了小体积校正。评估了剂量依赖性药物作用和与精神病理学的关联。患者在 6 个月的治疗期间出现双侧纹状体和海马体明显丢失。与对照组相比，低喹硫平剂量时纹状体体积丢失最为明显，高剂量时则不明显。事后分析表明，纹状体体积丢失在尾状核和壳核最为明显，而在伏隔核则不明显。相反，高喹硫平剂量时海马体体积丢失似乎更为明显。临床上，较高的基线阳性症状与随时间推移的更多纹状体和海马体丢失有关。尽管患者的脑室没有明显变化，但脑室增大与阴性症状改善较少相关。喹硫平治疗的首发精神分裂症患者的进行性区域性体积丢失可能与剂量有关且具有临床意义。进行性脑变化的潜在机制、特定的抗精神病药物化合物和临床症状需要进一步研究。
