Center for Cognitive Medicine (M/C 913), University of Illinois at Chicago, 912 South Wood Street, Suite 235, Chicago, IL 60612, USA.
Expert Rev Neurother. 2010 Jan;10(1):43-57. doi: 10.1586/ern.09.143.
Generalized cognitive impairments are stable deficits linked to schizophrenia and key factors associated with functional disability in the disorder. Preclinical data suggest that second-generation antipsychotics could potentially reduce cognitive impairments; however, recent large clinical trials indicate only modest cognitive benefits relative to first-generation antipsychotics. This might reflect a limited drug effect in humans, a differential drug effect due to brain alterations associated with schizophrenia, or limited sensitivity of the neuropsychological tests for evaluating cognitive outcomes. New adjunctive procognitive drugs may be needed to achieve robust cognitive and functional improvement. Drug discovery may benefit from greater utilization of translational neurocognitive biomarkers to bridge preclinical and clinical proof-of-concept studies, to optimize assay sensitivity, enhance cost efficiency, and speed progress in drug development.
广泛性认知障碍是与精神分裂症相关的稳定缺陷，也是导致该疾病功能障碍的关键因素。临床前数据表明，第二代抗精神病药可能具有潜在的改善认知作用；然而，最近的大型临床试验表明，与第一代抗精神病药相比，它们仅能带来适度的认知获益。这可能反映了人类的药物作用有限，也可能与精神分裂症相关的大脑改变导致药物作用存在差异，或者用于评估认知结果的神经心理学测试的敏感性有限。可能需要新的辅助认知药物来实现认知和功能的显著改善。药物研发可能受益于更多地利用转化神经认知生物标志物来连接临床前和临床概念验证研究，以优化检测灵敏度、提高成本效益，并加速药物开发进展。
