The predictive value of neural reward processing on exposure therapy outcome: Results from a randomized controlled trial.

BACKGROUND: Exposure is the gold standard treatment for phobic anxiety and is thought to represent the clinical application of extinction learning. Reward sensitivity might however also represent a predictive factor for exposure therapy outcome, as this therapy promotes positive experiences and involves positive comments by the therapist. We hypothesized that high reward sensitivity, as expressed by elevated reward expectancy and reward value, can be associated with better outcome to exposure therapy specifically. METHODS: Forty-four participants with a specific phobia for spiders were included in the current study. Participants were randomly assigned to exposure therapy (n = 25) or progressive muscle relaxation (PMR) (n = 19). Treatment outcome was defined as pre- versus post-therapy phobia symptoms. Before treatment, functional brain responses and behavioral responses (i.e. reaction time and accuracy) during reward anticipation and consumption were assessed with the Monetary Incentive Delay task (MID). Behavioral and neural responses in regions of interest (i.e. nucleus accumbens, ventromedial prefrontal cortex and the ventral tegmental area) as well as across the whole-brain were subsequently regressed on treatment outcomes. RESULTS: Exposure therapy was more effective in reducing phobia symptoms than PMR. Longer reaction times to reward cues and lower activation in the left posterior cingulate cortex during reward consumption were selectively associated with symptoms reductions following exposure therapy but not following PMR. Only within the exposure therapy group, greater symptom reduction was related to increased activation in the ventrolateral prefrontal cortex during reward anticipation, and decreased activation in the medial prefrontal cortex during reward consumption. CONCLUSION: Results indicate that individual differences in reward sensitivity can specifically predict exposure therapy outcome. Although activation in regions of interest were not related to therapy outcome, regions involved in attentional processing of reward cues were predictive of phobic symptom change following exposure therapy but not PMR.

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.

The shape of change in perceived stress, negative affect, and stress sensitivity during mindfulness-based stress reduction.

Both daily stress and the tendency to react to stress with heightened levels of negative affect (i.e., stress sensitivity) are important vulnerability factors for adverse mental health outcomes. Mindfulness-based stress reduction (MBSR) may help to reduce perceived daily stress and stress sensitivity. The purpose of this study was to examine how change in perceived stress, negative affect (NA), and the decoupling between perceived stress and NA evolved over the course of a MBSR program, without making any a priori assumptions on the shape of change. Seventy-one adults from the general population participating in MBSR provided daily diary assessments of perceived stress and NA during MBSR. The time-varying effect model (TVEM) indicated that perceived stress and NA decreased in a linear fashion rather than in a non-linear fashion, both as a function of time and as a function of the cumulative number of days of mindfulness practice. Both TVEM and multilevel growth modeling showed that the association between perceived stress and NA did not decrease over the course of MBSR. The findings support the hypothesis that MBSR reduces NA and also reduces the extent to which individuals perceive their days as stressful. Also, the results suggest that there is a dose-response relationship between the amount of mindfulness practice and reductions in daily stress and NA.

The Impact of Treatments for Depression on the Dynamic Network Structure of Mental States: Two Randomized Controlled Trials.

Evidence is growing that vulnerability to depression may be characterized by strong negative feedback loops between mental states. It is unknown whether such dynamics between mental states can be altered by treatment. This study examined whether treatment with imipramine or treatment with Mindfulness-Based Cognitive Therapy (MBCT) reduces the connectivity within dynamic networks of mental states in individuals with depressive symptoms. In the Imipramine trial, individuals diagnosed with major depression were randomized to imipramine treatment or placebo-pill treatment (n = 50). In the Mind-Maastricht trial, individuals with residual depressive symptoms were randomized to Mindfulness-Based Cognitive Therapy (MBCT) or to a waiting-list control condition (n = 119). Lagged associations among mental states, as assessed with the Experience Sampling Method (ESM), were estimated at baseline and post-intervention. The results show that few of the dynamic network connections changed significantly over time and few of the changes after MBCT and imipramine treatment differed significantly from the control groups. The decrease in average node connectivity after MBCT did not differ from the decrease observed in the waiting-list control group. Our findings suggest that imipramine treatment and MBCT do not greatly change the dynamic network structure of mental states, even though they do reduce depressive symptomatology.

Mindfulness training promotes upward spirals of positive affect and cognition: multilevel and autoregressive latent trajectory modeling analyses.

Recent theory suggests that positive psychological processes integral to health may be energized through the self-reinforcing dynamics of an upward spiral to counter emotion dysregulation. The present study examined positive emotion-cognition interactions among individuals in partial remission from depression who had been randomly assigned to treatment with mindfulness-based cognitive therapy (MBCT; n = 64) or a waitlist control condition (n = 66). We hypothesized that MBCT stimulates upward spirals by increasing positive affect and positive cognition. Experience sampling assessed changes in affect and cognition during 6 days before and after treatment, which were analyzed with a series of multilevel and autoregressive latent trajectory models. Findings suggest that MBCT was associated with significant increases in trait positive affect and momentary positive cognition, which were preserved through autoregressive and cross-lagged effects driven by global emotional tone. Findings suggest that daily positive affect and cognition are maintained by an upward spiral that might be promoted by mindfulness training.

Effects of mindfulness-based cognitive therapy on self-reported suicidal ideation: results from a randomised controlled trial in patients with residual depressive symptoms.

INTRODUCTION: The aim of the present study was to investigate the effects of mindfulness-based cognitive therapy (MBCT) on suicidal ideation in an open-label randomised controlled trial of patients with residual depressive symptoms. Furthermore, this study aimed at examining whether an effect of MBCT on suicidal ideation was dependent on a reduction in depression severity, worry and rumination, or an increase in mindfulness. METHODS: One hundred and thirty participants were randomised to a treatment arm (treatment as usual plus MBCT) or a wait list arm. Change in depression, change in worry, change in rumination and change in mindfulness were entered as covariates in a repeated measures ANOVA in order to assess to what degree MBCT-induced changes in suicidal ideation were independent from changes in these parameters. RESULTS: There was a significant group×time (pre vs. post) interaction on suicidal ideation indicating a significant reduction of suicidal ideation in the MBCT group, but not in the control group. The interaction remained significant after addition of the above covariates. Change in worry was the only covariate associated with change in suicidal ideation, causing a moderate reduction in the interaction effect size. CONCLUSIONS: The results suggest that MBCT may affect suicidal ideation in patients with residual depressive symptoms and that this effect may be mediated, in part, by participants' enhanced capacity to distance themselves from worrying thoughts.

How does MBCT for depression work? studying cognitive and affective mediation pathways.

UNLABELLED: Mindfulness based cognitive therapy (MBCT) is a non-pharmacological intervention to reduce current symptoms and to prevent recurrence of major depressive disorder. At present, it is not well understood which underlying mechanisms during MBCT are associated with its efficacy. The current study (n = 130) was designed to examine the roles of mindfulness skills, rumination, worry and affect, and the interplay between those factors, in the mechanisms of change in MBCT for residual depressive symptoms. An exploratory but systematic approach was chosen using Sobel-Goodman mediation analyses to identify mediators on the pathway from MBCT to reduction in depressive symptoms. We replicated earlier findings that therapeutic effects of MBCT are mediated by changes in mindfulness skills and worry. Second, results showed that changes in momentary positive and negative affect significantly mediated the efficacy of MBCT, and also mediated the effect of worry on depressive symptoms. Third, within the group of patients with a prior history of ≤ 2 episodes of MDD, predominantly changes in cognitive and to a lesser extent affective processes mediated the effect of MBCT. However, within the group of patients with a prior history of ≥ 3 episodes of MDD, only changes in affect were significant mediators for the effect of MBCT. TRIAL REGISTRATION: [corrected] Nederlands Trial Register NTR1084.

Putting a Hold on the Downward Spiral of Paranoia in the Social World: A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy in Individuals with a History of Depression.

CONTEXT: Paranoia embodies altered representation of the social environment, fuelling altered feelings of social acceptance leading to further mistrust. Mindfulness-based cognitive therapy (MBCT) may relieve paranoia and reduce its impact on social acceptance. OBJECTIVE: To determine whether MBCT alters momentary feeling of paranoia and social acceptance in daily life. DESIGN: Randomized controlled trial of daily-life repeated measures (up to 120 per participant) before and after allocation to MBCT or waiting list control. PARTICIPANTS: Volunteer sample of 130 eligible men and women with residual affective dysregulation after at least one episode of major depressive disorder. INTERVENTIONS: Eight weeks of MBCT in groups of 10-15 participants in addition to participants' usual treatment. OUTCOME MEASURES: Daily-life ratings of paranoia and social acceptance. This manuscript concerns additional analyses of the original trial; hypotheses were developed after data collection (focus initially on depressive symptoms) but before data analysis. RESULTS: Sixty-six participants were assigned to the waiting list control group and 64 to the MBCT intervention group, of whom 66 and 61 respectively were included in the per-protocol analyses. Intention-to-treat analyses revealed a significant group by time interaction in the model of momentary paranoia (b = -.18, p<0.001, d = -0.35) and social acceptance (b = .26, p<0.001, d = 0.41). Paranoia levels in the intervention group were significantly reduced (b = -.11, p<0.001) and feelings of social acceptance significantly increased (b = .18, p<0.001), whereas in the Control condition a significant increase in paranoia (b = .07, p = 0.008) and a decrease in social acceptance was apparent (b = -.09, p = 0.013). The detrimental effect of paranoia on social acceptance was significantly reduced in the MBCT, but not the control group (group by time interaction: b = .12, p = 0.022). CONCLUSIONS: MBCT confers a substantial benefit on subclinical paranoia and may interrupt the social processes that maintain and foster paranoia in individuals with residual affective dysregulation. TRIAL REGISTRATION: Netherlands Trial Register NTR1084.

Efficacy of mindfulness-based cognitive therapy in relation to prior history of depression: randomised controlled trial.

BACKGROUND: There appears to be consensus that patients with only one or two prior depressive episodes do not benefit from treatment with mindfulness-based cognitive therapy (MBCT). AIMS: To investigate whether the effect of MBCT on residual depressive symptoms is contingent on the number of previous depressive episodes (trial number NTR1084). METHOD: Currently non-depressed adults with residual depressive symptoms and a history of depression (≤2 prior episodes: n = 71; ≥3 episodes: n = 59) were randomised to MBCT (n = 64) or a waiting list (control: n = 66) in an open-label, randomised controlled trial. The main outcome measured was the reduction in residual depressive symptoms (Hamilton Rating Scale for Depression, HRSD-17). RESULTS: Mindfulness-based cognitive therapy was superior to the control condition across subgroups (ß = -0.56, P<0.001). The interaction between treatment and subgroup was not significant (ß = 0.45, P = 0.16). CONCLUSIONS: Mindfulness-based cognitive therapy reduces residual depressive symptoms irrespective of the number of previous episodes of major depression.

Mindfulness training increases momentary positive emotions and reward experience in adults vulnerable to depression: a randomized controlled trial.

OBJECTIVE: To examine whether mindfulness-based cognitive therapy (MBCT) increases momentary positive emotions and the ability to make use of natural rewards in daily life. METHOD: Adults with a life-time history of depression and current residual depressive symptoms (mean age = 43.9 years, SD = 9.6; 75% female; all Caucasian) were randomized to MBCT (n = 64) or waitlist control (CONTROL; n = 66) in a parallel, open-label, randomized controlled trial. The Experience Sampling Method was used to measure momentary positive emotions as well as appraisal of pleasant activities in daily life during 6 days before and after the intervention. Residual depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (Hamilton, 1960). RESULTS: MBCT compared to CONTROL was associated with significant increases in appraisals of positive emotion (b* = .39) and activity pleasantness (b* = .22) as well as enhanced ability to boost momentary positive emotions by engaging in pleasant activities (b* = .08; all ps < .005). Associations remained significant when corrected for reductions in depressive symptoms or for reductions in negative emotion, rumination, and worry. In the MBCT condition, increases in positive emotion variables were associated with reduction of residual depressive symptoms (all ps < .05). CONCLUSIONS: MBCT is associated with increased experience of momentary positive emotions as well as greater appreciation of, and enhanced responsiveness to, pleasant daily-life activities. These changes were unlikely to be pure epiphenomena of decreased depression and, given the role of positive emotions in resilience against depression, may contribute to the protective effects of MBCT against depressive relapse.

Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment.

BACKGROUND: Major depression has been associated cross-sectionally with increased cell-mediated immune activation but causality has been difficult to establish. This study prospectively investigated the hypothesis that baseline level of immune activation predicts the development of depression during interferon-alpha (IFN-alpha) treatment. METHODS: Sixteen hepatitis C patients without psychiatric disorder underwent IFN-alpha treatment. Proinflammatory and anti-inflammatory cytokines were determined before starting treatment. Presence of a major depressive disorder (MDD) was assessed at baseline and several times during treatment. RESULTS: Baseline soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were significantly increased in the five subjects that developed MDD during treatment compared with those that did not, with standardized effect sizes of 1.08, 1.16, and 1.25, respectively, controlling for marijuana use, cigarette smoking, and baseline level of depressive symptoms. CONCLUSIONS: Results suggest that increased immune activation, rather than an epiphenomenon, is a causal risk factor for the development of MDD.

Cytokines and major depression.

In the research field of psychoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. In this respect, there has been increasing interest in the putative involvement of the immune system in psychiatric disorders. In the present review, the role of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, in the aetiology and pathophysiology of major depression, is discussed. The 'cytokine hypothesis of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioural, neuroendocrine and neurochemical features of depressive disorders. This view is supported by various findings. Several medical illnesses, which are characterised by chronic inflammatory responses, e.g. rheumatoid arthritis, have been reported to be accompanied by depression. In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans. The central action of cytokines may also account for the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that is frequently observed in depressive disorders, as proinflammatory cytokines may cause HPA axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids (CSs) on the HPA axis. Concerning the deficiency in serotonergic (5-HT) neurotransmission that is concomitant with major depression, cytokines may reduce 5-HT levels by lowering the availability of its precursor tryptophan (TRP) through activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.