Webber Michael A, Marder Stephen R
Semel Institute for Neuroscience at UCLA, Mental Illness Research, Education, and Clinical Center, VA West Los Angeles Health Care Center, MIRECC 210A, 11301 Wilshire Boulevard, Los Angeles, CA 90073-1003, USA.
Curr Psychiatry Rep. 2008 Aug;10(4):352-8. doi: 10.1007/s11920-008-0056-8.
Despite the expansion of available antipsychotic drugs over the past 50 years, functional outcomes for individuals with schizophrenia have not markedly improved. These agents are efficacious for psychosis but do not adequately address other core domains of schizophrenia psychopathology, namely negative symptoms and cognitive impairment, which have a greater impact on functional outcomes, including vocational or academic performance and interpersonal relationships. In addition, treatment-refractory psychosis still precludes functional improvement in many patients. Schizophrenia is a clinical syndrome consisting of these domains, which likely have some disparities in their respective pathophysiologies. This suggests that drug development should look to other molecular targets besides the D2 receptor, which characterizes the mechanism of available medications for schizophrenia. In this report, we review novel pharmacologic approaches that aim to specifically address each individual domain of schizophrenia. The goal of this future pharmacotherapy strategy is to advance outcomes beyond psychosis remission and toward functional recovery.
尽管在过去50年里可用的抗精神病药物有所增加，但精神分裂症患者的功能结局并未显著改善。这些药物对精神病有效，但不能充分解决精神分裂症精神病理学的其他核心领域，即阴性症状和认知障碍，而这些对功能结局有更大影响，包括职业或学业表现以及人际关系。此外，难治性精神病仍然使许多患者无法实现功能改善。精神分裂症是一种由这些领域组成的临床综合征，其各自的病理生理学可能存在一些差异。这表明药物开发应寻找除D2受体之外的其他分子靶点，D2受体是现有精神分裂症药物作用机制的特征。在本报告中，我们回顾了旨在专门解决精神分裂症各个领域问题的新型药理学方法。这种未来药物治疗策略的目标是超越精神病缓解，实现功能恢复。
