Varastehmoradi Bardia, Wegener Gregers, Sanchez Connie, Smith Karen L
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
Alkermes, Inc., Biology, Waltham, Massachusetts, USA.
Behav Pharmacol. 2020 Apr;31(2&3):122-135. doi: 10.1097/FBP.0000000000000559.
A significant number of patients (30%) do not adequately respond to commonly prescribed antidepressants (e.g. SSRIs, SNRIs, and TCAs). Opioid receptors and their endogenous peptides have demonstrated a clear role in the regulation of mood in animal models and may offer an alternative approach to augment existing therapies. Nevertheless, there is an urgent need to find better ways to predict a patient's response to drug treatment, to improve overall drug responding, and to reduce the time to symptom remission using novel diagnostic and efficacy biomarkers. Cognitive processes, such as perception, attention, memory, and learning, are impaired in patients with mood disorders. These processes can be altered by emotions, a phenomenon called cognitive affective bias. Negative affective biases are a key feature of major depressive disorder (MDD) and may present concurrently with other cognitive deficits. Importantly, a significant percentage of patients report residual cognitive impairments even after effective drug treatment. This approach offers a new opportunity to predict patient treatment responses, potentially improving residual cognitive symptoms and patient outcomes. This review will (1) describe the underlying neurocircuitry of affective cognition and propose how negative biases may occur, (2) outline the role of opioid receptors in affective cognition, executive function, and MDD, and (3) present evidence from the published literature supporting a modulatory role for opioid drugs on negative affective bias, with a focus on kappa-opioid receptor antagonists, currently in development for clinical use for treatment-resistant MDD.
相当一部分患者（30%）对常用的抗抑郁药（如选择性5-羟色胺再摄取抑制剂、5-羟色胺-去甲肾上腺素再摄取抑制剂和三环类抗抑郁药）反应不佳。阿片受体及其内源性肽在动物模型的情绪调节中已显示出明确作用，可能为增强现有疗法提供一种替代方法。然而，迫切需要找到更好的方法来预测患者对药物治疗的反应，改善整体药物反应，并使用新型诊断和疗效生物标志物缩短症状缓解时间。认知过程，如感知、注意力、记忆和学习，在情绪障碍患者中会受损。这些过程会受到情绪的影响而改变，这种现象称为认知情感偏差。负性情感偏差是重度抑郁症（MDD）的一个关键特征，可能与其他认知缺陷同时出现。重要的是，相当比例的患者即使在有效药物治疗后仍报告有残留的认知障碍。这种方法为预测患者的治疗反应提供了新机会，有可能改善残留的认知症状和患者预后。本综述将（1）描述情感认知的潜在神经回路，并提出负性偏差可能如何发生，（2）概述阿片受体在情感认知、执行功能和MDD中的作用，以及（3）展示已发表文献中支持阿片类药物对负性情感偏差具有调节作用的证据，重点关注目前正在开发用于治疗难治性MDD临床应用的κ-阿片受体拮抗剂。
