Meyhöfer Inga, Kumari Veena, Hill Antje, Petrovsky Nadine, Ettinger Ulrich
1 Department of Psychology, University of Bonn, Bonn, Germany.
2 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
J Psychopharmacol. 2017 Apr;31(4):418-433. doi: 10.1177/0269881116675511. Epub 2016 Nov 11.
Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs.
目前的抗精神病药物无法令人满意地减轻阴性和认知症状，还会产生许多不良副作用，因此需要开发新的化合物。跨物种的实验行为模型系统可能有助于此类药物的研发。本研究的目的是进一步验证以下假设：当与精神分裂症的动眼生物标志物相结合时，控制性睡眠剥夺是一种安全有效的精神病模型系统。我们采用随机平衡的被试内设计，研究了32名健康参与者经历1晚完全睡眠剥夺后，对平稳跟踪眼动（SPEM）、前扫视（PS）、反扫视（AS）以及类似精神病状态的自我评分的影响。与正常睡眠对照夜相比，睡眠剥夺与SPEM速度增益降低、0.2赫兹时扫视频率增加、PS空间误差升高以及AS方向误差增加有关。睡眠剥夺还增加了SPEM、PS和AS测量的个体内变异性。此外，睡眠剥夺诱发了类似精神病的体验，包括幻觉、认知紊乱和阴性症状，这些体验又与AS方向误差存在中度关联。综上所述，睡眠剥夺导致了SPEM和AS表现出现类似精神病的损伤。然而，与精神分裂症的文献有所不同的是，睡眠剥夺还扰乱了PS控制。因此，睡眠剥夺是一个有前景但可能不具有特异性的实验模型，可能有助于进一步增进我们对精神病病理生理学潜在机制的理解，并有助于抗精神病药物和促认知药物的研发。
