Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA; Department of Psychology, University at Buffalo, Buffalo, NY, USA.
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jan 10;112:110407. doi: 10.1016/j.pnpbp.2021.110407. Epub 2021 Jul 25.
Clinical and preclinical studies have shown dysfunctions in genetic expression and neurotransmission of γ-Aminobutyric acid (GABA), GABA receptor subunits, and GABA-synthesizing enzymes GAD and GAD in schizophrenia. It is well documented that there is significant weight gain after chronic neuroleptic treatment in humans. While there are limited studies on the effects of diet on GABA signaling directly, a change in diet has been used clinically as an adjunct to treatment for schizophrenic relief. In this study, rats chronically consumed either a chow diet (CD) or a 60% high-fat diet (HFD) and drank from bottles that contained one of the following solutions: water, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg) for four weeks. Rats were then euthanized and their brains were processed for GABA in-vitro receptor autoradiography using [H] flunitrazepam. A chronic HFD treatment yielded significantly increased [H] flunitrazepam binding in the rat cerebellum independent of neuroleptic treatment. The desynchronization between the prefrontal cortex and the cerebellum is associated with major cognitive and motor dysfunctions commonly found in schizophrenic symptomatology, such as slowed reaction time, motor dyscoordination, and prefrontal activations related to speech fluency and cognitive alertness. These data support the notion that there is a dietary effect on GABA signaling within the cerebellum, as well as the importance of considering nutritional intervention methods as an adjunct treatment for patients chronically treated with neuroleptics. Finally, we indicate that future studies involving the analysis of individual patient's genetic profiles will further assist towards a precision medicine approach to the treatment of schizophrenia.
临床前和临床研究表明，精神分裂症患者存在γ-氨基丁酸（GABA）、GABA 受体亚单位和 GABA 合成酶 GAD 和 GAD 的基因表达和神经传递功能障碍。有大量文献记载，人类在接受慢性神经安定剂治疗后会显著增重。虽然关于饮食对 GABA 信号的直接影响的研究有限，但临床上已经将饮食改变作为精神分裂症缓解治疗的辅助手段。在这项研究中，大鼠长期摄入标准饮食（CD）或 60%高脂肪饮食（HFD），并从装有以下溶液之一的瓶子中饮水：水、氟哌啶醇（1.5mg/kg）或奥氮平（10mg/kg），持续四周。然后将大鼠安乐死，并对其大脑进行 GABA 体外受体放射自显影，使用 [H]氟硝西泮。慢性 HFD 处理导致大鼠小脑 [H]氟硝西泮结合显著增加，而与神经安定剂治疗无关。前额叶皮层和小脑之间的失同步与精神分裂症症状中常见的主要认知和运动功能障碍有关，例如反应时间减慢、运动协调障碍以及与言语流畅性和认知警觉性相关的前额叶激活。这些数据支持这样一种观点，即饮食对小脑内的 GABA 信号有影响，并且考虑营养干预方法作为慢性接受神经安定剂治疗的患者的辅助治疗方法非常重要。最后，我们指出，涉及分析个体患者遗传谱的未来研究将进一步有助于精神分裂症的精准医学治疗方法。
