Research Service, VA San Diego Healthcare System, United States; Department of Psychiatry, University of California, San Diego, United States.
Department of Psychiatry, University of California, San Diego, United States.
Schizophr Res. 2018 Mar;193:69-76. doi: 10.1016/j.schres.2017.06.042. Epub 2017 Jun 30.
Effortful motivation and reward valuation learning deficits are associated with negative symptoms and impaired cognition in schizophrenia (SZ) patients. Whereas clinical assessments of motivation and reward value typically rely upon clinician ratings or self-report scales, behavioral measures often confound these constructs. Simple reverse-translated behavioral tasks that independently quantify motivation and reward valuation-which could then be linked to cognition-may facilitate the development of pro-cognitive therapeutics by bridging the "preclinical-to-clinical" gap. This study determined whether novel behavioral measures of effortful motivation and reward valuation are associated with impaired cognition in SZ patients (n=36). Patients completed the Progressive Ratio Breakpoint task (PRBT; physical effort motivation) and the Probabilistic Learning Task (PLT; reward learning/valuation) in conjunction with the MATRICS Consensus Cognitive Battery (MCCB). SZ patients exhibited statistically significant deficits in global cognition and all individual MCCB subdomains. Significant correlations were observed between PRBT and MCCB global cognition (r=0.52), speed of processing (r=0.56) and attention vigilance (r=0.48) subdomains, but not with PLT or clinical symptoms. Results indicate that effort and reward learning deficits are dissociable targets that can improve our understanding of cognitive impairments associated among patients with SZ. More importantly, the results support the long-standing notion that the measurement of cognitive impairments in SZ is highly linked to a willingness to expend effort. The availability of a PRBT designed for use in both rodents and humans could improve our understanding of the nature of cognitive impairments in neuropsychiatric disorders and accelerate the development of novel pro-cognitive therapeutics.
努力动机和奖励估值学习缺陷与精神分裂症 (SZ) 患者的阴性症状和认知障碍有关。虽然动机和奖励价值的临床评估通常依赖于临床医生的评分或自我报告量表，但行为测量往往会混淆这些结构。简单的反向翻译行为任务可以独立量化动机和奖励估值，然后将其与认知联系起来，这可能通过弥合“临床前到临床”的差距来促进认知增强治疗的发展。本研究确定了新型努力动机和奖励估值行为测量是否与 SZ 患者的认知障碍有关 (n=36)。患者完成了递增比率断点任务 (PRBT；身体努力动机) 和概率学习任务 (PLT；奖励学习/估值)，同时完成了 MATRICS 共识认知电池 (MCCB)。SZ 患者在整体认知和所有单个 MCCB 子领域均表现出统计学上显著的缺陷。在 PRBT 和 MCCB 整体认知 (r=0.52)、处理速度 (r=0.56) 和注意力警觉性 (r=0.48) 子领域之间观察到显著相关性，但与 PLT 或临床症状无关。结果表明，努力和奖励学习缺陷是可分离的靶点，可以提高我们对 SZ 患者认知障碍的理解。更重要的是，结果支持了一个长期存在的观点，即 SZ 认知障碍的测量与付出努力的意愿高度相关。用于啮齿动物和人类的 PRBT 的可用性可以提高我们对神经精神障碍认知障碍本质的理解，并加速新型认知增强治疗的开发。
