Tamminga Carol A
Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas 75390-9070, USA.
J Clin Psychiatry. 2006;67 Suppl 9:9-13; discussion 36-42.
Currently, no drugs exist that effectively treat cognition in people with schizophrenia. What is known about the neurobiology of cognition in schizophrenia is derived from the animal literature; it is inadequate and superficial. Despite this lack, pharmacologic research into potential molecular targets has uncovered several viable possibilities from animal studies. A subcommittee of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) program investigated the range of putative molecular targets for treating cognition. Those targets that show promise for pharmacologic focus include the dopamine receptors (especially D1) in the prefrontal cortex (PFC), the serotonin receptors in the PFC and anterior cingulate cortex, the glutamatergic excitatory synapse, the acetylcholine nicotinic receptors in the hippocampus, the acetylcholine muscarinic receptors, and the brain gamma-aminobutyric acid (GABA) system. Once developed and tested, the effective compounds will be valuable for the treatment of the symptom domains of cognitive dysfunction and negative symptoms.
目前,尚无有效治疗精神分裂症患者认知功能的药物。关于精神分裂症认知神经生物学的了解源于动物研究文献;这些了解并不充分且较为肤浅。尽管存在这一不足,但针对潜在分子靶点的药理学研究已从动物研究中发现了几种可行的可能性。改善精神分裂症认知的测量与治疗研究(MATRICS)项目的一个小组委员会调查了治疗认知的一系列假定分子靶点。那些显示出有药理学研究重点潜力的靶点包括前额叶皮质(PFC)中的多巴胺受体(尤其是D1)、PFC和前扣带回皮质中的5-羟色胺受体、谷氨酸能兴奋性突触、海马体中的乙酰胆碱烟碱受体、乙酰胆碱毒蕈碱受体以及脑γ-氨基丁酸(GABA)系统。一旦研发并经过测试,有效的化合物将对治疗认知功能障碍和阴性症状的症状领域具有重要价值。