Biomedical Sciences Institute, Federal University of Rio de Janeiro, RJ, Brazil; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Schizophr Res. 2019 May;207:80-92. doi: 10.1016/j.schres.2018.04.028. Epub 2018 May 3.
Mounting evidence indicates that schizophrenia is a disorder that stems from maladaptive plasticity within neural circuits and produces broad cognitive deficits leading to loss of autonomy. A large number of studies have identified abnormalities spanning many neurotransmitter systems in schizophrenia, and as a result, a variety of drugs have been developed to attempt to treat these abnormalities and enhance cognition. Unfortunately, positive results have been limited so far. This may be in part because the scope of abnormalities in the schizophrenic brain requires a treatment capable of engaging many different neurotransmitter systems. One approach to achieving this kind of treatment has been to use neuroplasticity-based computerized cognitive training programs to stimulate the formation of more adaptive circuits. Although the number of studies implementing this approach has increased exponentially in recent years, effect sizes for cognitive gains have been modest and adherence to treatment remains an important challenge in many studies, as patients are often required to train for 40 h or more. In the present paper, we argue that cognitive training protocols will benefit from the addition of cognitive enhancers to produce more robust and longer lasting targeted neuroplasticity. Indeed, recent data from animal studies have provided support for combining plasticity-enhancing drugs with tailored behavioral training paradigms to restore normal function within dysfunctioning neural circuits. The advantages and challenges of applying this approach to patients with schizophrenia will be discussed.
越来越多的证据表明，精神分裂症是一种源自神经回路适应性不良可塑性的疾病，会导致广泛的认知缺陷，进而丧失自主性。大量研究已经确定了精神分裂症中跨越许多神经递质系统的异常，因此开发了多种药物来尝试治疗这些异常并增强认知能力。不幸的是，迄今为止，积极的结果有限。这可能部分是因为精神分裂症患者大脑中的异常范围需要一种能够作用于许多不同神经递质系统的治疗方法。实现这种治疗的一种方法是使用基于神经可塑性的计算机认知训练计划来刺激更具适应性的回路的形成。尽管近年来实施这种方法的研究数量呈指数级增长，但认知收益的效果大小适中，并且在许多研究中，对治疗的依从性仍然是一个重要的挑战，因为患者通常需要训练 40 小时或更长时间。在本文中，我们认为认知训练方案将受益于添加认知增强剂以产生更强大和更持久的靶向神经可塑性。事实上，最近来自动物研究的数据为将增强可塑性的药物与定制的行为训练范式相结合以恢复功能失调的神经回路中的正常功能提供了支持。将这种方法应用于精神分裂症患者的优点和挑战将进行讨论。
