Understanding mechanisms of depression prevention: study protocol of a randomized cross-over trial to investigate mechanisms of mindfulness and positive fantasizing as intervention techniques for reducing perseverative cognition in remitted depressed individuals.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders, and involves high relapse rates in which persistent negative thinking and rumination (i.e., perseverative cognition [PC]) play an important role. Positive fantasizing and mindfulness are common evidence-based psychological interventions that have been shown to effectively reduce PC and subsequent depressive relapse. How the interventions cause changes in PC over time, is unknown, but likely differ between the two. Whereas fantasizing may change the valence of thought content, mindfulness may operate through disengaging from automatic thought patterns. Comparing mechanisms of both interventions in a clinical sample and a non-clinical sample can give insight into the effectivity of interventions for different individuals. The current study aims to 1) test whether momentary psychological and psychophysiological indices of PC are differentially affected by positive fantasizing versus mindfulness-based interventions, 2) test whether the mechanisms of change by which fantasizing and mindfulness affect PC differ between remitted MDD versus never-depressed (ND) individuals, and 3) explore potential moderators of the main effects of the two interventions (i.e., what works for whom). METHODS: In this cross-over trial of fantasizing versus mindfulness interventions, we will include 50 remitted MDD and 50 ND individuals. Before the start of the measurements, participants complete several individual characteristics. Daily-life diary measures of thoughts and feelings (using an experience sampling method), behavioural measures of spontaneous thoughts (using the Sustained Attention to Response Task), actigraphy, physiological measures (impedance cardiography, electrocardiography, and electroencephalogram), and measures of depressive mood (self-report questionnaires) are performed during the week before (pre-) the interventions and the week during (peri-) the interventions. After a wash-out of at least one month, pre- and peri-intervention measures for the second intervention are repeated. DISCUSSION: This is the first study integrating self-reports, behavioural-, and physiological measures capturing dynamics at multiple time scales to examine the differential mechanisms of change in PC by psychological interventions in individuals remitted from multiple MDD episodes and ND individuals. Unravelling how therapeutic techniques affect PC in remitted individuals might generate insights that allows development of personalised targeted relapse prevention interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06145984, November 16, 2023.

Understanding and predicting future relapse in depression from resting state functional connectivity and self-referential processing.

BACKGROUND: The recurrent nature of Major Depressive Disorder (MDD) asks for a better understanding of mechanisms underlying relapse. Previously, self-referential processing abnormalities have been linked to vulnerability for relapse. We investigated whether abnormalities in self-referential cognitions and functioning of associated brain-networks persist upon remission and predict relapse. METHODS: Remitted recurrent MDD patients (n = 48) and never-depressed controls (n = 23) underwent resting-state fMRI scanning at baseline and were additionally assessed for their implicit depressed self-associations and ruminative behaviour. A template-based dual regression approach was used to investigate between-group differences in default mode, cingulo-opercular and frontoparietal network resting-state functional connectivity (RSFC). Additional prediction of relapse status at 18-month follow-up was investigated within patients using both regression analyses and machine learning classifiers. RESULTS: Remitted patients showed higher rumination, but no implicit depressed self-associations or RSFC abnormalities were observed between patients and controls. Nevertheless, relapse was related to i) baseline RSFC between the ventral default mode network and the precuneus, dorsomedial frontal gyrus, and inferior occipital lobe, ii) implicit self-associations, and iii) uncontrollability of ruminative thinking, when controlled for depressive symptomatology. Moreover, preliminary machine learning classifiers demonstrated that RSFC within the investigated networks predicted relapse on an individual basis. CONCLUSIONS: Remitted MDD patients seem to be commonly characterized by abnormal rumination, but not by implicit self-associations or abnormalities in relevant brain networks. Nevertheless, relapse was predicted by self-related cognitions and default mode RSFC during remission, suggesting that variations in self-relevant processing play a role in the complex dynamics associated with the vulnerability to developing recurrent depressive episodes. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, August 18, 2015, trial number NL53205.042.15.

The impact of mood-induction on maladaptive thinking in the vulnerability for depression.

BACKGROUND AND OBJECTIVES: Mind-wandering, and specifically the frequency and content of mind-wandering, plays an important role in the psychological well-being of individuals. Repetitive negative thinking has been associated with a high risk to develop and maintain Major Depressive Disorder. We here combined paradigms and techniques from cognitive sciences and experimental clinical psychology to study the transdiagnostic psychiatric phenomenon of repetitive negative thinking. This allowed us to investigate the adjustability of the content and characteristics of mind-wandering in individuals varying in their susceptibility to negative affect. METHODS: Participants high (n = 42) or low (n = 40) on their vulnerability for negative affect and depression performed a Sustained Attention to Response Task (SART) after a single session of positive fantasizing and a single session of stress induction in a cross-over design. Affective states were measured before and after the interventions. RESULTS: After stress, negative affect increased, while after fantasizing both positive affect increased and negative affect decreased. Thoughts were less off-task, past-related and negative after fantasizing compared to after stress. Individuals more susceptible to negative affect showed more off-task thinking after stress than after fantasizing compared to individuals low on this. LIMITATIONS: In this cross-over design, no baseline measurement was included, limiting comparison to 'uninduced' mind-wandering. Inclusion of self-related concerns in the SART could have led to negative priming. CONCLUSIONS: Stress-induced negative thinking underlying vulnerability for depression could be partially countered by fantasizing in a non-clinical sample, which may inform the development of treatments for depression and other disorders characterized by maladaptive thinking.