Wolf Daniel H, Satterthwaite Theodore D, Kantrowitz Jacob J, Katchmar Natalie, Vandekar Lillie, Elliott Mark A, Ruparel Kosha
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
Department of Radiology, University of Pennsylvania, Philadelphia, PA.
Schizophr Bull. 2014 Nov;40(6):1328-37. doi: 10.1093/schbul/sbu026. Epub 2014 Mar 22.
Motivational deficits play a central role in disability caused by schizophrenia and constitute a major unmet therapeutic need. Negative symptoms have previously been linked to hypofunction in ventral striatum (VS), a core component of brain motivation circuitry. However, it remains unclear to what extent this relationship holds for specific negative symptoms such as amotivation, and this question has not been addressed with integrated behavioral, clinical, and imaging measures. Here, 41 individuals with schizophrenia and 37 controls performed a brief, computerized progressive ratio task (PRT) that quantifies effort exerted in pursuit of monetary reward. Clinical amotivation was assessed using the recently validated Clinical Assessment Interview for Negative Symptoms (CAINS). VS function was probed during functional magnetic resonance imaging using a monetary guessing paradigm. We found that individuals with schizophrenia had diminished motivation as measured by the PRT, which significantly and selectively related to clinical amotivation as measured by the CAINS. Critically, lower PRT motivation in schizophrenia was also dimensionally related to VS hypofunction. Our results demonstrate robust dimensional associations between behavioral amotivation, clinical amotivation, and VS hypofunction in schizophrenia. Integrating behavioral measures such as the PRT will facilitate translational efforts to identify biomarkers of amotivation and to assess response to novel therapeutic interventions.
动机缺陷在精神分裂症所致残疾中起核心作用，是一个尚未满足的主要治疗需求。此前，阴性症状与腹侧纹状体（VS）功能减退有关，腹侧纹状体是脑动机回路的核心组成部分。然而，这种关系在诸如无动机等特定阴性症状中在多大程度上成立仍不清楚，并且这个问题尚未通过综合行为、临床和影像学测量来解决。在此，41名精神分裂症患者和37名对照者完成了一项简短的计算机化累进比率任务（PRT），该任务可量化为追求金钱奖励而付出的努力。使用最近验证的阴性症状临床评估访谈（CAINS）评估临床无动机情况。在功能磁共振成像期间，使用金钱猜测范式探究VS功能。我们发现，通过PRT测量，精神分裂症患者的动机减弱，这与通过CAINS测量的临床无动机显著且选择性相关。至关重要的是，精神分裂症患者较低的PRT动机在维度上也与VS功能减退相关。我们的结果表明，精神分裂症患者的行为无动机、临床无动机和VS功能减退之间存在稳健的维度关联。整合诸如PRT等行为测量将有助于开展转化研究，以识别无动机的生物标志物并评估对新型治疗干预的反应。
