A randomized controlled trial of cognitive control training (CCT) as an add-on treatment for late-life depression: a study protocol

Background Already a major health concern, late-life depression (LLD) is expected to form an increasing problem in the aging population. Moreover, despite current treatments, LLD is associated with a poor long-term prognosis and high rate of chronicity. Treatment provision and treatment accordingly warrant improvement, where add-on treatments might contribute to the efficacy of conventional therapies. Although it is known that impaired cognitive control contributes to LDD, it is not targeted sufficiently by current interventions. Research on cognitive control training (CCT) shows promising results on depressive symptoms, cognitive performance, and overall functioning. However, further research is needed to determine the long-term effects of CCT on LLD, its cost-effectiveness, and mechanisms of change. Methods In the current multicenter randomized controlled trial (RCT) with a between-subjects design participants aged 60 years and over with a current LLD receiving treatment as usual (TAU) are randomized to add-on CCT or placebo training. Randomization is stratified by depression severity. Participants will receive eight online CCT or placebo sessions spread across four consecutive weeks. They will complete a post-training assessment after 1 month and three follow-up assessments scheduled three, six and 12 months after completing the training. We expect CCT and TAU to be more (cost-)effective in reducing depressive symptoms than placebo training and TAU. Additionally, we will be looking at secondary clinical, cognitive and global functioning outcomes and likely mechanisms of change (e.g., improved cognitive functioning, reduced rumination, and improved inhibition of negative stimuli). Discussion The proposed RCT aims to contribute to the clinical and scientific knowledge on the long-term effects of CCT as an add-on treatment for LLD. Cost-effectiveness is particularly relevant considering the expected volume of the target demographic. The study will be a pragmatic trial with few inclusion restrictions, providing information on feasibility of web-based trainings in clinical settings. The outcomes are potentially generalizable to guidelines for treatment of LLD. Trial registration This trial is registered in the Netherlands Trial Register (code: NL7639). Registered 3 april 2019.

Feasibility of computerised positive mental imagery training as a treatment adjunct in in-patient mental health settings: randomised controlled trial

Background Positive affect and anhedonia are important but challenging targets for mental health treatments. Previous research indicates the potential of a computerised cognitive training paradigm involving generation of positive mental imagery, termed positive mental imagery training (PMIT), to increase positive affect and reduce anhedonia. Aims Our main aim was to investigate the feasibility of PMIT as a positive affect-focused, transdiagnostic adjunct to treatment as usual for patients in in-patient mental health settings. Method We ran an open feasibility, randomised controlled trial with three parallel arms: treatment as usual; treatment as usual plus PMIT; and treatment as usual plus an active comparator, cognitive control training. Fifty-seven patients from two different in-patient mental health treatment clinics in Germany were randomised in a 1:1:1 ratio. PMIT and cognitive control training comprised an introductory session followed by eight 15-min training sessions over 2 weeks. Clinical outcomes such as positive affect (primary outcome measure) and anhedonia were assessed at pre- and post-training, and at a further 2-week follow-up. Results Adherence was good and attrition was low. The patterns of results for the outcome data were not consistent with a specific effect of PMIT on positive affect, but were more consistent with a specific effect on anhedonia. Conclusions The results indicate feasibility and potential promise of a larger efficacy trial investigating PMIT as a treatment adjunct in in-patient mental health settings. Limitations include lack of researcher blinding, small sample size and lack of pre-specified feasibility outcomes. Anhedonia may be a more suitable primary outcome for a future larger trial.

Punishment on Pause: Preliminary Evidence That Mindfulness Training Modifies Neural Responses in a Reactive Aggression Task

Reactive aggression, a hostile retaliatory response to perceived threat, has been attributed to failures in emotion regulation. Interventions for reactive aggression have largely focused on cognitive control training, which target top-down emotion regulation mechanisms to inhibit aggressive impulses. Recent theory suggests that mindfulness training (MT) improves emotion regulation via both top-down and bottom-up neural mechanisms and has thus been proposed as an alternative treatment for aggression. Using this framework, the current pilot study examined how MT impacts functional brain physiology in the regulation of reactive aggression. Participants were randomly assigned to 2 weeks of MT (n = 11) or structurally equivalent active coping training (CT) that emphasizes cognitive control (n = 12). Following training, participants underwent functional magnetic resonance imaging (fMRI) during a retaliatory aggression task, a 16-trial game in which participants could respond to provocation by choosing whether or not to retaliate in the next round. Training groups did not differ in levels of aggression displayed. However, participants assigned to MT exhibited enhanced ventromedial prefrontal cortex (vmPFC) recruitment during punishment events (i.e., the aversive consequence of losing) relative to those receiving active CT. Conversely, the active coping group demonstrated greater dorsomedial prefrontal cortex (dmPFC) activation when deciding how much to retaliate, in line with a bolstered top-down behavior monitoring function. The findings suggest that mindfulness and cognitive control training may regulate aggression via different neural circuits and at different temporal stages of the provocation-aggression cycle.Trial Registration: identification no. NCT03485807.

Preventing Recurrence of Depression: Long-Term Effects of a Randomized Controlled Trial on Cognitive Control Training for Remitted Depressed Patients

Previous studies suggest that cognitive control training (CCT) shows potential as a preventive intervention for depression. In this study, the first to examine long-term preventive effects of CCT, we examined effects on (a) task-specific cognitive transfer at 1-year follow-up, (b) recurrence of depression, and (c) functioning over the course of a year. Each of 92 remitted depressed patients were randomly assigned to a CCT condition or an active control condition (ACT). Effects of training were monitored using weekly assessments of emotion regulation, cognitive complaints, depressive symptoms, and resilience (brief weekly questionnaire). At 1-year follow-up, participants completed a structured clinical interview, cognitive transfer task, and questionnaires. We observed task-specific cognitive transfer ( p < .001, d = 1.23) and lower recurrence rates in the CCT condition ( p = .04; odds ratio = 0.38). However, no long-term beneficial effects of training were observed on the weekly ratings of functioning, and groups did not differ in performance on the self-report questionnaires at 1-year follow-up.