BACKGROUND 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. METHODS 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. DISCUSSION 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 Trial registration: Netherlands Trial Register, August 18, 2015, trial number NL5219.

中文翻译：

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预防缓解的复发性抑郁症复发的神经认知工作机制（NEWPRIDE）：预防性认知治疗的随机对照神经影像学试验方案。

背景技术重度抑郁症（MDD）是一种具有高度复发性的精神疾病，使得预防复发成为重要的临床目标。预防性认知疗法（PCT）已被证明对预防复发有效，尽管并非对每个患者都有效。更好地了解复发易感性和预防性治疗的工作机制可能有助于制定有效的个性化干预策略。MDD的神经认知模型表明，在情绪处理和调节过程中对边缘情绪处理区域的前额叶控制异常对理解复发易感性很重要。目前尚不清楚这些神经认知异常的变化是否由PCT诱导，从而在介导复发性抑郁的风险中起重要作用。在预防抑郁症复发的神经认知工作机制（NEWPRIDE）中，我们的目的是：1）研究支持复发易感性的神经认知因素，2）了解PCT的神经认知工作机制，3）根据预后预测纵向治疗效果治疗的神经认知特征，以及4）验证瞳孔扩张反应是前额叶活动的标志，反映情绪调节能力和治疗成功。方法在该随机对照试验中，将包括75例缓解的复发性MDD（rrMDD）患者。在基线和三个月的随访中将进行详细的临床和认知测量，fMRI扫描和瞳孔测定。在此间隔内，将把50名rrMDD患者随机分配到PCT的八次会议中，将25名rrMDD患者分配到等待名单中。在基线时 将另外包括25名健康对照参与者，以使rrMDD中的横断面残留神经认知异常成为现实。18个月后，对复发状态进行临床评估，以调查哪种疗法引起的变化预测了分配给PCT的50例患者中的复发。讨论本试验是第一个研究复发和介导预防复发的神经认知脆弱性因素，它们在预测PCT成功方面的价值以及瞳孔扩张在这方面是否可作为重要标志的研究。最终，对复发预防的更深入了解可能有助于开发更有针对性的预防性干预措施。试用注册：荷兰试用注册，2015年8月18日，试用号NL5219。