Exploring the relation between visual mental imagery and affect in the daily life of previously depressed and never depressed individuals.

Previously depressed individuals experience disturbances in affect. Affective disturbances may be related to visual mental imagery, given that imagery-based processing of emotional stimuli causes stronger affective responses than verbal processing in experimental laboratory studies. However, the role of imagery-based processing in everyday life is unknown. This study assessed mental imagery in the daily life of previously and never depressed individuals. Higher levels of visual mental imagery was hypothesised to be associated with more affective reactivity to both negatively and positively valenced mental representations. This study was the first to explore mental imagery in daily life using experience sampling methodology. Previously depressed (n = 10) and matched never depressed (n = 11) individuals participated in this study. Momentary affect and imagery-based processing were assessed using the "Imagine your mood" smartphone application. Participants recorded on average 136 momentary reports over a period of 8 weeks. The expected association between visual mental imagery and affective reactivity was not found. Unexpectedly, in both previously and never depressed individuals, higher levels of imagery-based processing of mental representations in daily life were significantly associated with better momentary mood and more positive affect, regardless of valence. The causality of effects remains to be examined in future studies.

Differential impact of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment on affect fluctuations and individual affect networks and impact on relapse: a secondary analysis of a randomised controlled trial.

Background: There is an urgent need to better understand and prevent relapse in major depressive disorder (MDD). We explored the differential impact of various MDD relapse prevention strategies (pharmacological and/or psychological) on affect fluctuations and individual affect networks in a randomised setting, and their predictive value for relapse. Methods: We did a secondary analysis using experience sampling methodology (ESM) data from individuals with remitted recurrent depression that was collected alongside a randomised controlled trial that ran in the Netherlands, comparing: (I) tapering antidepressants while receiving preventive cognitive therapy (PCT), (II) combining antidepressants with PCT, or (III) continuing antidepressants without PCT, for the prevention of depressive relapse, as well as ESM data from 11 healthy controls. Participants had multiple past depressive episodes, but were remitted for at least 8 weeks and on antidepressants for at least six months. Exclusion criteria were: current (hypo)mania, current alcohol or drug abuse, anxiety disorder that required treatment, psychological treatment more than twice per month, a diagnosis of organic brain damage, or a history of bipolar disorder or psychosis. Fluctuations (within-person variance, root mean square of successive differences, autocorrelation) in negative and positive affect were calculated. Changes in individual affect networks during treatment were modelled using time-varying vector autoregression, both with and without applying regularisation. We explored whether affect fluctuations or changes in affect networks over time differed between treatment conditions or relapse outcomes, and predicted relapse during 2-year follow-up. This ESM study was registered at ISRCTN registry, ISRCTN15472145. Findings: Between Jan 1, 2014, and Jan 31, 2015, 72 study participants were recruited, 42 of whom were included in the analyses. We found no indication that affect fluctuations differed between treatment groups, nor that they predicted relapse. We observed large individual differences in affect network structure across participants (irrespective of treatment or relapse status) and in healthy controls. We found no indication of group-level differences in how much networks changed over time, nor that changes in networks over time predicted time to relapse (regularised models: hazard ratios [HR] 1063, 95% CI <0.0001->10 000, p = 0.65; non-regularised models: HR 2.54, 95% CI 0.23-28.7, p = 0.45) or occurrence of relapse (regularised models: odds ratios [OR] 22.84, 95% CI <0.0001->10 000, p = 0.90; non-regularised models: OR 7.57, 95% CI 0.07-3709.54, p = 0.44) during complete follow-up. Interpretation: Our findings should be interpreted with caution, given the exploratory nature of this study and wide confidence intervals. While group-level differences in affect dynamics cannot be ruled out due to low statistical power, visual inspection of individual affect networks also revealed no meaningful patterns in relation to MDD relapse. More studies are needed to assess whether affect dynamics as informed by ESM may predict relapse or guide personalisation of MDD relapse prevention in daily practice. Funding: The Netherlands Organisation for Health Research and Development, Dutch Research Council, University of Amsterdam.

Redefining Therapeutic Outcomes of Depression Treatment.

Responses to evidence-based interventions for depression are divergent: Some patients benefit more than others during treatment and some do not benefit at all or even deteriorate. Tailoring interventions to the individual may improve outcomes. However, such personalization of evidence-based treatment in depression requires investigation of individual outcomes and the individual trajectories towards these outcomes. This theoretical paper provides a critical reflection on individual outcomes of depression treatment. First, it is argued that outcomes should be broadened, from a focus on mainly depressive symptomatology to recovery in different domains. It is acknowledged that recovery from depression reflects a personal journey that differs from person to person. Second, outcome measures should be lengthened beyond the acute treatment phase, taking a lifetime perspective on depression. The challenge then is to discover which trajectories of what measures during what interventions result in personalized sustainable recovery and for whom. Routine outcome monitoring systems may be used to inform this quest towards assessment of personalized sustainable therapeutic outcomes. Adaptations to broaden and lengthen measurements in routine outcome monitoring systems are proposed to identify predictors of personalized sustainable recovery. Routine outcome monitoring systems may eventually be used to implement personalized treatments for depression that result in personalized sustainable recovery.

The effect of mind-body and aerobic exercise on negative symptoms in schizophrenia: A meta-analysis.

OBJECTIVE: This meta-analysis aims to evaluate the effects of different types of physical exercise (PE) on negative symptoms in schizophrenia patients. Mind-body exercise (MBE), aerobic exercise (AE) and resistance training (RT) will be investigated. METHOD: The Cochrane Library, Medline, Embase and PsycINFO were searched from their inception until April 26, 2018. Randomized controlled trials comparing PE with any control group in patients with schizophrenia were included when negative symptoms had been assessed. This meta-analysis was conducted according to the PRISMA guidelines. The methodological quality of the included studies was assessed with the Cochrane Risk of Bias assessment tool. Moderator, sensitivity, and meta regression analyses were conducted to explore causes of heterogeneity and impact of study quality. RESULTS: We included 22 studies (N = 1249). The overall methodological quality was poor. The meta-analysis (random effects model) showed a medium significant effect in favor of any PE intervention (Hedges' g = 0.434, 95% CI = 0.196-0.671) versus any control condition. MBE and AE respectively showed a medium significant effect (Hedges' g = 0.461) and a small significant effect (Hedges' g = 0.341) versus any control condition. The effect of RT could not be examined. The overall heterogeneity was high (I2 = 76%) and could not be reduced with moderator or sensitivity analyses. CONCLUSION: This meta-analysis demonstrated that PE could be a promising intervention in the treatment of negative symptoms. However, the quality of the included studies was low and heterogeneity was high, which makes it impossible to make a clear recommendation. Therefore, results should be interpreted with care.

Cost-effectiveness, cost-utility and the budget impact of antidepressants versus preventive cognitive therapy with or without tapering of antidepressants.

BACKGROUND: As depression has a recurrent course, relapse and recurrence prevention is essential.AimsIn our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/-AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact. METHOD: Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model. RESULTS: Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/-AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/-AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/-AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/-AD. CONCLUSIONS: Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/-AD will become cost-effective.Declaration of interestC.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.

Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial.

BACKGROUND: Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence. METHODS: In this single-blind, multicentre, parallel, three-group, randomised controlled trial, individuals recruited by general practitioners, pharmacists, secondary mental health care, or media were randomly assigned (10:10:8) to PCT and antidepressants, antidepressants alone, or PCT with tapering of antidepressants, using computer-generated randomised allocation stratified for number of previous depressive episodes and type of care. Eligible participants had previously experienced at least two depressive episodes and were in remission or recovery on antidepressants, which they had been receiving for at least the past 6 months. Exclusion criteria were current mania or hypomania, a history of bipolar disorder, any history of psychosis, current alcohol or drug abuse, an anxiety disorder that requires treatment, psychological treatment more than twice a month, and a diagnosis of organic brain damage. The primary outcome was time-related proportion of individuals with depressive relapse or recurrence in the intention-to-treat population, assessed four times in 24 months. Assessors were masked to treatment allocation, whereas physicians and participants could not be masked. This trial is registered with the Netherlands Trial Register, number NTR1907. FINDINGS: Between July 14, 2009, and April 30, 2015, 2486 participants were assessed for eligibility and 289 were randomly assigned to PCT and antidepressant (n=104), antidepressant alone (n=100), or PCT with tapering of antidepressant (n=85). The overall log-rank test was significant (p=0·014). Antidepressants alone were not superior to PCT while tapering off antidepressants in terms of the risk of relapse or recurrence (hazard ratio [HR] 0·86, 95% CI 0·56-1·32; p=0·502). Adding PCT to antidepressant treatment resulted in a 41% relative risk reduction compared with antidepressants alone (0·59, 0·38-0·94; p=0·026). There were two suicide attempts (one in the antidepressants alone group and one in the PCT with tapering of antidepressants group) and one death (in the PCT and antidepressants group) not related to the interventions during the 24 months' follow-up. INTERPRETATION: Maintenance antidepressant treatment is not superior to PCT after recovery, whereas adding PCT to antidepressant treatment after recovery is superior to antidepressants alone. PCT should be offered to recurrently depressed individuals on antidepressants and to individuals who wish to stop antidepressants after recovery. FUNDING: The Netherlands Organisation for Health Research and Development.

Imagine your mood: Study design and protocol of a randomized controlled micro-trial using app-based experience sampling methodology to explore processes of change during relapse prevention interventions for recurrent depression.

BACKGROUND: Relapse prevention strategies include continuation of antidepressant medication and preventive psychological interventions. This study aims to gain understanding that may inform tailoring of relapse prevention to individual differences, to improve their effects. Such treatment personalization may be based on repeated assessments within one individual, using experience sampling methodology. As a first step towards informing decisions based on this methodology, insight is needed in individual differences in risk of relapse and response to treatment, and how relapse prevention strategies may differentially target vulnerability for relapse. METHODS: The smartphone application 'Imagine your mood' has been developed specifically for this study to assess emotions, imagery, cognitions, and behaviors in daily life. Parallel to the randomized controlled trial 'Disrupting the rhythm of depression', 45 remitted recurrently depressed individuals taking continuation antidepressant medication will be randomly assigned to either continuing antidepressant medication (n = 15), continuing antidepressant medication combined with an eight-session preventive cognitive therapy (n = 15), or tapering of antidepressant medication in combination with preventive cognitive therapy (n = 15). Relapse and return of depressive symptomatology over a 24-month follow-up will be assessed. Additionally, matched never depressed individuals (n = 15) will be recruited as controls. DISCUSSION: This innovative study combines the strengths of a randomized controlled trial and experience sampling methodology in a micro-trial to explore individual differences in risk of relapse and what works for whom to prevent relapse. Results may ultimately pave the way for therapists to tailor relapse prevention strategies to individual (affective) vulnerability. TRIAL REGISTRATION: ISRCTN15472145, retrospectively registered.

Rethinking a Negative Event: The Affective Impact of Ruminative versus Imagery-Based Processing of Aversive Autobiographical Memories.

INTRODUCTION: Ruminative (abstract verbal) processing during recall of aversive autobiographical memories may serve to dampen their short-term affective impact. Experimental studies indeed demonstrate that verbal processing of non-autobiographical material and positive autobiographical memories evokes weaker affective responses than imagery-based processing. In the current study, we hypothesized that abstract verbal or concrete verbal processing of an aversive autobiographical memory would result in weaker affective responses than imagery-based processing. METHODS: The affective impact of abstract verbal versus concrete verbal versus imagery-based processing during recall of an aversive autobiographical memory was investigated in a non-clinical sample (n = 99) using both an observational and an experimental design. Observationally, it was examined whether spontaneous use of processing modes (both state and trait measures) was associated with impact of aversive autobiographical memory recall on negative and positive affect. Experimentally, the causal relation between processing modes and affective impact was investigated by manipulating the processing mode during retrieval of the same aversive autobiographical memory. RESULTS: Main findings were that higher levels of trait (but not state) measures of both ruminative and imagery-based processing and depressive symptomatology were positively correlated with higher levels of negative affective impact in the observational part of the study. In the experimental part, no main effect of processing modes on affective impact of autobiographical memories was found. However, a significant moderating effect of depressive symptomatology was found. Only for individuals with low levels of depressive symptomatology, concrete verbal (but not abstract verbal) processing of the aversive autobiographical memory did result in weaker affective responses, compared to imagery-based processing. DISCUSSION: These results cast doubt on the hypothesis that ruminative processing of aversive autobiographical memories serves to avoid the negative emotions evoked by such memories. Furthermore, findings suggest that depressive symptomatology is associated with the spontaneous use and the affective impact of processing modes during recall of aversive autobiographical memories. Clinical studies are needed that examine the role of processing modes during aversive autobiographical memory recall in depression, including the potential effectiveness of targeting processing modes in therapy.

Imagery Rescripting: The Impact of Conceptual and Perceptual Changes on Aversive Autobiographical Memories.

BACKGROUND: Imagery rescripting (ImRs) is a process by which aversive autobiographical memories are rendered less unpleasant or emotional. ImRs is thought only to be effective if a change in the meaning-relevant (semantic) content of the mental image is produced, according to a cognitive hypothesis of ImRs. We propose an additional hypothesis: that ImRs can also be effective by the manipulation of perceptual features of the memory, without explicitly targeting meaning-relevant content. METHODS: In two experiments using a within-subjects design (both N = 48, community samples), both Conceptual-ImRs-focusing on changing meaning-relevant content-and Perceptual-ImRs-focusing on changing perceptual features-were compared to Recall-only of aversive autobiographical image-based memories. An active control condition, Recall + Attentional Breathing (Recall+AB) was added in the first experiment. In the second experiment, a Positive-ImRs condition was added-changing the aversive image into a positive image that was unrelated to the aversive autobiographical memory. Effects on the aversive memory's unpleasantness, vividness and emotionality were investigated. RESULTS: In Experiment 1, compared to Recall-only, both Conceptual-ImRs and Perceptual-ImRs led to greater decreases in unpleasantness, and Perceptual-ImRs led to greater decreases in emotionality of memories. In Experiment 2, the effects on unpleasantness were not replicated, and both Conceptual-ImRs and Perceptual-ImRs led to greater decreases in emotionality, compared to Recall-only, as did Positive-ImRs. There were no effects on vividness, and the ImRs conditions did not differ significantly from Recall+AB. CONCLUSIONS: Results suggest that, in addition to traditional forms of ImRs, targeting the meaning-relevant content of an image during ImRs, relatively simple techniques focusing on perceptual aspects or positive imagery might also yield benefits. Findings require replication and extension to clinical samples.

EMDR and mindfulness. Eye movements and attentional breathing tax working memory and reduce vividness and emotionality of aversive ideation.

BACKGROUND AND OBJECTIVES: Eye Movement Desensitization and Reprocessing (EMDR) and Mindfulness-Based Cognitive Therapy (MBCT) are effective in reducing the subjective impact of negative ideation. In both treatments, patients are encouraged to engage in a dual-task (eye movements (EM) in the case of EMDR and attentional breathing (AB) in the case of MBCT) while they experience negative thoughts or images. Working memory theory explains the effects of EM by suggesting that it taxes limited working memory resources, thus rendering the image less vivid and emotional. It was hypothesized that both AB and EM tax working memory and that both reduce vividness and emotionality of negative memories. METHODS: Working memory taxation by EM and AB was assessed in healthy volunteers by slowing down of reaction times. In a later session, participants retrieved negative memories during recall only, recall + EM and recall + AB (study 1). Under improved conditions the study was replicated (study 2). RESULTS: In both studies and to the same degree, attentional breathing and eye movements taxed working memory. Both interventions reduced emotionality of memory in study 1 but not in study 2 and reduced vividness in study 2 but not in study 1. LIMITATIONS: EMDR is more than EM and MBCT is more than AB. Memory effects were assessed by self reports. CONCLUSIONS: EMDR and MBCT may (partly) derive their beneficial effects from taxing working memory during recall of negative ideation.