Ettinger Ulrich, Kumari Veena
Department of Psychology, University of Bonn, Bonn, Germany.
Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust, London, UK.
Lancet Psychiatry. 2015 Nov;2(11):1028-35. doi: 10.1016/S2215-0366(15)00313-2.
Development of drugs for the treatment of the clinical symptoms and cognitive deficits of schizophrenia is unsatisfactory, with many initially promising compounds not showing beneficial effects in clinical studies. Experimental model systems of schizophrenia combined with well-validated biomarkers are urgently needed to provide early indicators of effectiveness. Herein, we argue that experimentally controlled sleep deprivation represents a translational model system that can be studied in combination with neurocognitive biomarkers. Specifically, we review data on the psychotomimetic effects of sleep deprivation in healthy human beings and provide evidence of the psychosis-like deficits in translational inhibitory biomarkers-prepulse inhibition and antisaccades-that occur after sleep deprivation. These data support the use of the sleep deprivation model in combination with biomarkers with excellent psychometric properties and well-characterised neural mechanisms, such as prepulse inhibition and antisaccades, to substantially advance development of drugs with antipsychotic or pro-cognitive effects.
用于治疗精神分裂症临床症状和认知缺陷的药物研发并不理想，许多最初前景看好的化合物在临床研究中并未显示出有益效果。迫切需要将精神分裂症实验模型系统与经过充分验证的生物标志物相结合，以提供有效性的早期指标。在此，我们认为实验控制的睡眠剥夺代表了一种可与神经认知生物标志物联合研究的转化模型系统。具体而言，我们回顾了关于健康人睡眠剥夺的拟精神病效应的数据，并提供了睡眠剥夺后在转化抑制性生物标志物——前脉冲抑制和反扫视中出现的类精神病缺陷的证据。这些数据支持将睡眠剥夺模型与具有优异心理测量特性和特征明确的神经机制的生物标志物（如前脉冲抑制和反扫视）相结合使用，以大幅推进具有抗精神病或促认知作用药物的研发。
