Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 2, 9713 AW, Groningen, The Netherlands.
Department of Psychiatry and Urban Mental Health Institute, Amsterdam University Medical Center, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
BMC Psychiatry. 2019 Dec 19;19(1):409. doi: 10.1186/s12888-019-2384-0.
Major Depressive Disorder (MDD) is a psychiatric disorder with a highly recurrent character, making prevention of relapse an important clinical goal. Preventive Cognitive Therapy (PCT) has been proven effective in preventing relapse, though not for every patient. A better understanding of relapse vulnerability and working mechanisms of preventive treatment may inform effective personalized intervention strategies. Neurocognitive models of MDD suggest that abnormalities in prefrontal control over limbic emotion-processing areas during emotional processing and regulation are important in understanding relapse vulnerability. Whether changes in these neurocognitive abnormalities are induced by PCT and thus play an important role in mediating the risk for recurrent depression, is currently unclear. In the Neurocognitive Working Mechanisms of the Prevention of Relapse In Depression (NEWPRIDE) study, we aim to 1) study neurocognitive factors underpinning the vulnerability for relapse, 2) understand the neurocognitive working mechanisms of PCT, 3) predict longitudinal treatment effects based on pre-treatment neurocognitive characteristics, and 4) validate the pupil dilation response as a marker for prefrontal activity, reflecting emotion regulation capacity and therapy success.
In this randomized controlled trial, 75 remitted recurrent MDD (rrMDD) patients will be included. Detailed clinical and cognitive measurements, fMRI scanning and pupillometry will be performed at baseline and three-month follow-up. In the interval, 50 rrMDD patients will be randomized to eight sessions of PCT and 25 rrMDD patients to a waiting list. At baseline, 25 healthy control participants will be additionally included to objectify cross-sectional residual neurocognitive abnormalities in rrMDD. After 18 months, clinical assessments of relapse status are performed to investigate which therapy induced changes predict relapse in the 50 patients allocated to PCT.
The present trial is the first to study the neurocognitive vulnerability factors underlying relapse and mediating relapse prevention, their value for predicting PCT success and whether pupil dilation acts as a valuable marker in this regard. Ultimately, a deeper understanding of relapse prevention could contribute to the development of better targeted preventive interventions.
Trial registration: Netherlands Trial Register, August 18, 2015, trial number NL5219.
重度抑郁症（MDD）是一种具有高度复发性的精神障碍，因此预防复发是一个重要的临床目标。预防认知疗法（PCT）已被证明能有效预防复发，但并非对每个患者都有效。更好地了解复发的脆弱性和预防治疗的作用机制，可以为有效的个性化干预策略提供信息。MDD 的神经认知模型表明，在情绪处理和调节过程中，前额叶对边缘情绪处理区域的控制异常是理解复发脆弱性的重要因素。PCT 是否会引起这些神经认知异常的改变，以及这些改变是否在介导复发性抑郁的风险中起重要作用，目前尚不清楚。在《预防抑郁复发的神经认知工作机制研究》（NEWPRIDE）中，我们旨在：1）研究导致复发脆弱性的神经认知因素，2）了解 PCT 的神经认知作用机制，3）根据治疗前的神经认知特征预测纵向治疗效果，4）验证瞳孔扩张反应作为反映情绪调节能力和治疗成功的前额叶活动的标志物。
在这项随机对照试验中，将纳入 75 名缓解后复发性 MDD（rrMDD）患者。在基线和 3 个月随访时，将进行详细的临床和认知测量、功能磁共振成像扫描和瞳孔测量。在此期间，将 50 名 rrMDD 患者随机分为 8 节 PCT 组，25 名 rrMDD 患者分为等待名单组。在基线时，还将另外纳入 25 名健康对照参与者，以客观 rrMDD 患者的横断面残留神经认知异常。18 个月后，进行临床评估以调查预测 50 名接受 PCT 治疗的患者复发状态的治疗诱导变化。
本试验是首次研究复发相关的神经认知脆弱性因素及其在预防复发中的中介作用，评估它们对预测 PCT 成功的价值，以及瞳孔扩张在这方面是否是一个有价值的标志物。最终，对预防复发的深入了解可能有助于开发更有针对性的预防干预措施。
试验注册：荷兰临床试验注册中心，2015 年 8 月 18 日，试验编号 NL5219。
