Lui Su, Li Tao, Deng Wei, Jiang Lijun, Wu Qizhu, Tang Hehan, Yue Qiang, Huang Xiaoqi, Chan Raymond C, Collier David A, Meda Shashwath A, Pearlson Godfrey, Mechelli Andrea, Sweeney John A, Gong Qiyong
Huaxi MR Research Center, Department of Radiology, State Key Lab of Biotherapy,West China Hospital of Sichuan University, Chengdu, China.
Arch Gen Psychiatry. 2010 Aug;67(8):783-92. doi: 10.1001/archgenpsychiatry.2010.84.
Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural system effects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophrenia before and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments.
To examine alterations of regional and neural network function in antipsychotic-naive patients with first-episode schizophrenia before and after treatment with second-generation antipsychotic medication.
Case-control study.
Huaxi MR Research Center and Mental Health Centre of the West China Hospital.
Thirty-four antipsychotic-naive patients with first-episode schizophrenia were scanned using gradient-echo echo-planar imaging while in a resting state. After 6 weeks of antipsychotic treatment, patients were rescanned. Thirty-four matched healthy control subjects were studied at baseline for comparison purposes.
The amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent signals, believed to reflect spontaneous neural activity, was used to characterize regional cerebral function. Functional connectivity across brain regions was evaluated using a seed voxel correlation approach and an independent component analysis. Changes in these measures after treatment were examined to characterize effects of antipsychotic drugs on regional function and functional integration.
After short-term treatment with second-generation antipsychotic medications, patients showed increased ALFF, particularly in the bilateral prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. Increased regional ALFF was associated with a reduction of clinical symptoms, and a widespread attenuation in functional connectivity was observed that was correlated with increased regional ALFF.
We demonstrate for the first time, to our knowledge, that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied by decreased integration of function across widely distributed neural networks. These findings contribute to the understanding of the complex systems-level effects of antipsychotic drugs.
我们目前所了解的抗精神病药物作用大多处于受体水平，与介导其临床疗效的神经系统效应相距甚远。在药物治疗前后，对未使用过抗精神病药物的精神分裂症患者的脑功能进行研究，有助于加深对这些临床有效治疗方法的治疗机制的理解。
研究未使用过抗精神病药物的首发精神分裂症患者在接受第二代抗精神病药物治疗前后区域和神经网络功能的变化。
病例对照研究。
华西磁共振研究中心和华西医院精神卫生中心。
34名未使用过抗精神病药物的首发精神分裂症患者在静息状态下使用梯度回波平面成像进行扫描。在接受6周抗精神病药物治疗后，对患者进行再次扫描。选取34名匹配的健康对照者在基线时进行研究以作比较。
采用血氧水平依赖信号的低频波动幅度（ALFF）来表征区域脑功能，该指标被认为可反映自发神经活动。使用种子体素相关方法和独立成分分析评估脑区之间的功能连接。检查治疗后这些指标的变化，以表征抗精神病药物对区域功能和功能整合的影响。
在接受第二代抗精神病药物短期治疗后，患者的ALFF增加，尤其是在双侧前额叶和顶叶皮质、左侧颞上皮质和右侧尾状核。区域ALFF的增加与临床症状的减轻相关，并且观察到功能连接广泛减弱，这与区域ALFF的增加相关。
据我们所知，我们首次证明抗精神病药物治疗后会出现广泛的区域同步神经活动增加，同时广泛分布的神经网络之间的功能整合减少。这些发现有助于理解抗精神病药物在复杂系统水平上的作用。
