Blunted amygdala activity is associated with depression severity in treatment-resistant depression

Up to 50% of individuals with major depressive disorder (MDD) do not recover after two antidepressant medication trials, and therefore meet the criteria for treatment-resistant depression (TRD). Mindfulness-based cognitive therapy (MBCT) is one promising treatment; however, the extent to which MBCT influences clinical outcomes relative to baseline neural activation remains unknown. In the present study we investigated baseline differences in amygdala activation between TRD patients and healthy controls (HCs), related amygdala activation to depression symptoms, and examined the impacts of MBCT and amygdala activation on longitudinal depression outcomes. At baseline, TRD patients (n = 80) and HCs (n = 37) participated in a functional magnetic resonance imaging task in which they identified either the emotion (affect labeling) or the gender (gender labeling) of faces, or passively viewed faces (observing). The TRD participants then completed eight weeks of MBCT or a health enhancement program (HEP). Relative to HCs, the TRD patients demonstrated less amygdala activation during affect labeling, and marginally less during gender labeling. Blunted amygdala activation in TRD patients during affect labeling was associated with greater depression severity. MBCT was associated with greater depression reductions than was HEP directly following treatment; however, at 52 weeks the treatment effect was not significant, and baseline amygdala activation across the task conditions predicted depression severity in both groups. TRD patients have blunted amygdala responses during affect labeling that are associated with greater concurrent depression. Furthermore, although MBCT produced greater short-term improvements in depression than did HEP, overall baseline amygdala reactivity was predictive of long-term clinical outcomes in both groups.     

The effects of mindfulness-based cognitive therapy on recurrence of depressive episodes, mental health and quality of life: A randomized controlled study

Depression is characterized by a large risk of relapse/recurrence. Mindfulness-based cognitive therapy (MBCT) is a recent non-drug psychotherapeutic intervention to prevent future depressive relapse/recurrence in remitted/recovered depressed patients. In this randomized controlled trial, the authors investigated the effects of MBCT on the relapse in depression and the time to first relapse since study participation, as well as on several mood states and the quality of life of the patients. 106 recovered depressed patients with a history of at least 3 depressive episodes continued either with their treatment as usual (TAU) or received MBCT in addition to TAU. The efficacy of MBCT was assessed over a study period of 56 weeks. At the end of the study period relapse/recurrence was significantly reduced and the time until first relapse increased in the MBCT plus TAU condition in comparison with TAU alone. The MBCT plus TAU group also showed a significant reduction in both short and longer-term depressive mood and better mood states and quality of the life. For patients with a history of at least three depressive episodes who are not acutely depressed, MBCT, added to TAU, may play an important role in the domain of relapse prevention in depression.     

The Persistent Case of Major Depression: An Argument for Long-Term Treatment

According to psychotherapy outcome literature, treatments for major depressive disorder (MDD) yield impressive results. Study after study demonstrates the efficacy of brief, evidence-based interventions for depressed individuals. Nevertheless, MDD continues to exact a devastating toll on modern society. The World Health Organization has identified it as the leading cause of disability worldwide. This reality is surprising given the implications from the academic literature. A historical analysis of MDD treatment suggests that most people with MDD experienced complete remission and enhanced outcomes when long-term, psychodynamically influenced treatments prevailed. An analysis of the system that perpetuates the brief intervention model for MDD, managed care, is discussed. This analysis is followed by a case study that illustrates the harm managed care can do to patients with MDD who are not permitted treatment of longer duration. Implications and recommendations for psychologists to intervene at the micro and macro levels are discussed.     

Mindfulness‐based cognitive therapy is effective as relapse prevention for patients with recurrent depression in Scandinavian primary health care

This study examined the effectiveness of mindfulness‐based cognitive therapy (MBCT) in primary care for patients with recurrent depression (major depressive disorder: MDD). According to the World Health Organization (WHO), MDD is now the leading cause of disease burden in middle‐ and high‐income countries. Patients (N = 45) with three or more previous depressive episodes were recruited to participate in MBCT as a preventative intervention. Using a benchmarking approach, outcome data was compared with data from a recent efficacy study. The methodology is a rigorous approach to assessing effectiveness when evidence‐based UK protocols are transferred into the existing Scandinavian service delivery. Additionally, a person‐centred methodological approach was used to assess clinical significance on the Reliable Change Index (RCI). The analysis revealed comparable or larger effects from pre‐test to post‐test in reduced psychiatric symptoms, increased quality of life and level of mindfulness, and the effects were maintained over 14 months. Analysis of the relapse rate in the current study (16%) compared to the TAU in the efficacy study (68%) yielded an h value of 0.78, a moderate effect size. Only 13% dropped out of the treatment. According to the RCI findings, 65% to 67% of participants in the clinical group improved, no individual worsened, and women showed a significantly greater improvement of depression and anxiety than men. Therapeutic alliance and motivation had no impact on the outcome. The overall result suggests that MBCT can be implemented successfully in Scandinavian primary health care as a preventive intervention for patients with recurrent depression.     

How does mindfulness-based cognitive therapy work?

Mindfulness-based cognitive therapy (MBCT) is an efficacious psychosocial intervention for recurrent depression ( [Kuyken et?al., 2008], [Ma and Teasdale, 2004] and [Teasdale et?al., 2000]). To date, no compelling research addresses MBCT’s mechanisms of change. This study determines whether MBCT’s treatment effects are mediated by enhancement of mindfulness and self-compassion across treatment, and/or by alterations in post-treatment cognitive reactivity. The study was embedded in a randomized controlled trial comparing MBCT with maintenance antidepressants (mADM) with 15-month follow-up (Kuyken et al., 2008). Mindfulness and self-compassion were assessed before and after MBCT treatment (or at equivalent time points in the mADM group). Post-treatment reactivity was assessed one month after the MBCT group sessions or at the equivalent time point in the mADM group. One hundred and twenty-three patients with ≥3 prior depressive episodes, and successfully treated with antidepressants, were randomized either to mADM or MBCT. The MBCT arm involved participation in MBCT, a group-based psychosocial intervention that teaches mindfulness skills, and discontinuation of ADM. The mADM arm involved maintenance on a therapeutic ADM dose for the duration of follow-up. Interviewer-administered outcome measures assessed depressive symptoms and relapse/recurrence across 15-month follow-up. Mindfulness and self-compassion were measured using self-report questionnaire. Cognitive reactivity was operationalized as change in depressive thinking during a laboratory mood induction.MBCT’s effects were mediated by enhancement of mindfulness and self-compassion across treatment. MBCT also changed the nature of the relationship between post-treatment cognitive reactivity and outcome. Greater reactivity predicted worse outcome for mADM participants but this relationship was not evident in the MBCT group.MBCT’s treatment effects are mediated by augmented self-compassion and mindfulness, along with a decoupling of the relationship between reactivity of depressive thinking and poor outcome. This decoupling is associated with the cultivation of self-compassion across treatment.     

Mindfulness-Based Cognitive Therapy for Neuroticism (Stress Vulnerability): A Pilot Randomized Study

Objective: Neuroticism, a characteristic associated with increased stress vulnerability and the tendency to experience distress, is strongly linked to risk of different forms of psychopathology. However, there are few evidence-based interventions to target neuroticism. This pilot study investigated the efficacy and acceptability of mindfulness-based cognitive therapy (MBCT) compared with an online self-help intervention for individuals with high levels of neuroticism. The MBCT was modified to address psychological processes that are characteristic of neuroticism. Method: Participants with high levels of neuroticism were randomized to MBCT (n = 17) or an online self-help intervention (n = 17). Self-report questionnaires were administered preintervention and again at 4 weeks postintervention. Results: Intention-to-treat analyses found that MBCT participants had significantly lower levels of neuroticism postintervention than the control group. Compared with the control group, the MBCT group also experienced significant reductions in rumination and increases in self-compassion and decentering, of which the latter two were correlated with reductions in neuroticism within the MBCT group. Low drop-out rates, high levels of adherence to home practice, and positive feedback from MBCT participants provide indications that this intervention may be an acceptable form of treatment for individuals who are vulnerable to becoming easily stressed. Conclusions: MBCT specifically modified to target neuroticism-related processes is a promising intervention for reducing neuroticism. Results support evidence suggesting neuroticism is malleable and amenable to psychological intervention. MBCT for neuroticism warrants further investigation in a larger study.     

Extensions and Mechanisms of Mindfulness‐based Cognitive Therapy: A Review of the Evidence

Mindfulness‐based cognitive therapy (MBCT) was originally developed to prevent depressive relapse and recurrence and has also been widely extended to new patient populations and target problems over the last 14 years. We provide a comprehensive review of this literature, examining the strength of the evidence base for specific populations and target problems and identifying questions for future research to address. Specifically, we review studies addressing the use of MBCT for depressive disorders (prevention of depressive relapse and treatment of residual and current depressive symptoms), the use of MBCT in the treatment or management of other mental disorders (bipolar disorder, anxiety disorders, mixed anxiety and depression symptoms, disordered eating, personality disorders, and psychosis), and the use of MBCT in behavioural medicine contexts. Additionally, we discuss the extension of MBCT during specific developmental periods, like childhood, pregnancy and post‐partum, and adult caregiving, and, finally, we address the use of MBCT among clinical health‐care providers. In the second section, we review hypothesised mechanisms of change in MBCT and reflect on implications for theories of how MBCT works in the application to various patient populations and target problems. We also consider research addressing active ingredients and what is known about the “dosage” of meditation practice. We conclude with a summary of recommendations for future research.     

An Open Trial of Telephone-Delivered Mindfulness-Based Cognitive Therapy: Feasibility,Acceptability, and Preliminary Efficacy for Reducing Depressive Symptoms

Mindfulness-based cognitive therapy (MBCT) is a promising intervention for reducing depressive symptoms in individuals with comorbid chronic disease, but the program’s attendance demands make it inaccessible to many who might benefit. We tested the feasibility, acceptability, safety, and preliminary efficacy of an abbreviated, telephone-delivered adaptation of the in-person mindfulness-based cognitive therapy (MBCT-T) program in a sample of patients with depressive symptoms and hypertension.Participants (n = 14; 78.6% female, mean age = 60.6) with mild to moderate depressive symptoms and hypertension participated in the 8-week MBCT-T program. Feasibility was indexed via session attendance and home-based practice completion. Acceptability was indexed via self-reported satisfaction scores. Safety was assessed via reports of symptomatic decline or need for additional mental health treatment. Depressive symptoms (Quick Inventory of Depressive Symptomatology–Self-Report [QIDS-SR]) and anxiety (Hospital Anxiety and Depression Scale—Anxiety subscale; HADS-A) were assessed at baseline and immediately following the intervention.Sixty-four percent of participants (n = 9) attended ≥4 intervention sessions. Seventy-one percent (n = 6) of participants reported completing all assigned formal home practice and 89.2% (n = 8) reported completing all assigned informal practice. Participants were either very satisfied (75%; n = 6) or mostly satisfied (25%; n = 2) with the intervention. There were no adverse events or additional need for mental health treatment. Depressive symptom scores were 4.09 points lower postintervention (p = .004). Anxiety scores were 3.18 points lower postintervention (p = .039).Results support the feasibility, acceptability, safety, and preliminary efficacy of an abbreviated, telephone-delivered version of MBCT for reducing depressive and anxiety symptoms in individuals with co-occurring chronic disease.     

Cognitive vulnerability to depression in individuals with borderline personality disorder

The goal of the current study was to examine whether individuals with comorbid Major Depressive Disorder (MDD) and Borderline Personality Disorder (BPD) exhibit greater severity of depressive symptoms than (1) individuals with MDD without BPD and (2) individuals with neither MDD nor BPD. One hundred and forty-one individuals participated in a semi-structured clinical interview assessing MDD and BPD. They also completed measures assessing depressive symptoms, depressogenic attributional style, hopelessness, self-esteem, rumination, and dysfunctional attitudes. In line with hypotheses, individuals with BPD and MDD exhibited higher levels of depressive symptoms and cognitive vulnerability than individuals in the other two groups. In addition, after controlling for the effects of cognitive vulnerability, the effect of group membership on depressive symptoms was reduced, suggesting that the increased severity of depressive symptoms experienced by those with BPD is partially due to their possessing higher levels of cognitive vulnerability to depression.     

Cognitive reactivity as outcome and working mechanism of mindfulness-based cognitive therapy for recurrently depressed patients in remission

Major depressive disorder is a prevalent condition with high relapse rates. There is evidence that cognitive reactivity is an important vulnerability factor for the recurrence of depression. Mindfulness-based interventions are designed to reduce relapse rates, with cognitive reactivity as one of the proposed working mechanisms. In a randomised controlled trial we compared the effect of mindfulness-based cognitive therapy (MBCT) with treatment-as-usual (TAU) on cognitive reactivity in recurrently depressed patients (N?=?115). Depressive symptoms, cognitive reactivity, and mindfulness skills were assessed pre and post treatment. Patients in the MBCT group reported a significantly greater reduction in cognitive reactivity than those in the TAU group (d?=?.51). The reduction of cognitive reactivity appeared to mediate the association between MBCT/TAU and decrease of depressive symptoms, using pre and post scores. The current study provides evidence that MBCT reduces cognitive reactivity and preliminary evidence that cognitive reactivity is a working mechanism of MBCT.     

Non-pharmacological treatment-related changes of molecular biomarkers in major depressive disorder: A systematic review and meta-analysis

BackgroundMajor depressive disorder (MDD) is a serious mood disorder and leading cause of disability. Despite treatment advances, approximately 30% of individuals with MDD do not achieve adequate clinical response. Better understanding the biological mechanism(s) underlying clinical response to specific psychopharmacological interventions may help fine tune treatments in order to further modulate their underlying mechanisms of action. However, little is known regarding the effect of non-pharmacological treatments (NPTs) on candidate molecular biomarker levels in MDD. This review aims to identify molecular biomarkers that may elucidate NPT response for MDD.MethodsWe performed a systematic review and a multilevel linear mixed-effects meta-analyses, and a meta-regression. Searches were performed in PubMed, Scopus, and PsycINFO in October 2020 and July 2021.ResultsFrom 1387 retrieved articles, 17 and six studies were included in the systematic review and meta-analyses, respectively. Although there was little consensus associating molecular biomarker levels with symptomology and/or treatment response, brain metabolites accessed via molecular biomarker-focused neuroimaging techniques may provide promising information on whether an individual with MDD would respond positively to NPTs. Furthermore, non-invasive brain stimulation interventions significantly increased the expression of neurotrophic factors (NTFs) compared to sham/placebo, regardless of add-on pharmacological treatment.ConclusionsNTFs are candidate biomarkers to fine-tune NIBS for MDD treatment.     

Memory of faces: a slow wave ERP study of major depression

This study examined slow wave (SW) event-related brain potential (ERP) amplitudes in response to happy, neutral, and sad faces during a working memory task to further identify the associated component processes and physiological changes of mood-congruent memory biases in individuals with and without major depression. The results suggest that individuals with and without a diagnosis of major depressive disorder (MDD) differentially maintain valenced facial information in their working memory. Specifically, the nondepressed individuals displayed a marked reduction in SW amplitude to the negative faces. Individuals with MDD exhibited equivalent SW amplitudes for positive and negative facial stimuli. Results are discussed in terms of avoidance coping, previous ERP studies of working memory, and facial recognition deficits in individuals with MDD.     

Relapse/Recurrence Prevention in Major Depressive Disorder: 26-Month Follow-Up of Mindfulness-Based Cognitive Therapy Versus an Active Control

We conducted a 26-month follow-up of a previously reported 12-month study that compared mindfulness-based cognitive therapy (MBCT) to a rigorous active control condition (ACC) for depressive relapse/recurrence prevention and improvements in depressive symptoms and life satisfaction. Participants in remission from major depression were randomized to an 8-week MBCT group (n = 46) or the ACC (n = 46). Outcomes were assessed at baseline; postintervention; and 6, 12, and 26 months. Intention-to-treat analyses indicated no differences between groups for any outcome over the 26-month follow-up. Time to relapse results (MBCT vs. ACC) indicated a hazard ratio = .82, 95% CI [.34, 1.99]. Relapse rates were 47.8% for MBCT and 50.0% for ACC. Piecewise analyses indicated that steeper declines in depressive symptoms in the MBCT vs. the ACC group from postintervention to 12 months were not maintained after 12 months. Both groups experienced a marginally significant rebound of depressive symptoms after 12 months but were still improved at 26 months compared to baseline (b = –4.12, p <= .008). Results for life satisfaction were similar. In sum, over a 26-month follow-up, MBCT was no more effective for preventing depression relapse/recurrence, reducing depressive symptoms, or improving life satisfaction than a rigorous ACC. Based on epidemiological data and evidence from prior depression prevention trials, we discuss the possibility that both MBCT and ACC confer equal therapeutic benefit. Future studies that include treatment as usual (TAU) control conditions are needed to confirm this possibility and to rule out the potential role of time-related effects. Overall findings underscore the importance of comparing MBCT to TAU as well as to ACCs.     

Emotional reactivity to daily events in major and minor depression

Although emotional dysfunction is an important aspect of major depressive disorder (MDD), it has rarely been studied in daily life. Peeters, Nicolson, Berkhof, Delespaul, and deVries (2003) observed a surprising mood-brightening effect when individuals with MDD reported greater reactivity to positive events. To better understand this phenomenon, we conducted a multimethod assessment of emotional reactivity to daily life events, obtaining detailed reports of appraisals and event characteristics using the experience-sampling method and the Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004) in 35 individuals currently experiencing a major depressive episode, 26 in a minor depressive (mD) episode, and 38 never-depressed healthy controls. Relative to healthy controls, both mood-disordered groups reported greater daily negative affect and lower positive affect and reported events as less pleasant, more unpleasant, and more stressful. Importantly, MDD and mD individuals reported greater reductions in negative affect following positive events, an effect that converged across assessment methods and was not explained by differences in prevailing affect, event appraisals, or medications. Implications of this curious mood-brightening effect are discussed.     

The impact of depression on abstinence self-efficacy and substance use outcomes among emerging adults in residential treatment

A large proportion of emerging adults treated for substance use disorder (SUD) present with symptoms of negative affect and major depressive disorder (MDD). However, little is known regarding how these comorbidities influence important mechanisms of treatment response, such as increases in abstinence self-efficacy (ASE). This study tested the degree to which MDD and/or depressive symptoms interacted with during-treatment changes in ASE and examined these variables' relation to outcome at 3 months' posttreatment. Participants (N = 302; 74% male) completed measures at intake, midtreatment, end-of-treatment, and at 3-month follow-up. ASE was measured with the Alcohol and Drug Use Self-Efficacy (ADUSE) scale; depressive symptoms were assessed with the Brief Symptom Inventory 18 (BSI 18) Depression scale; and current MDD diagnoses were deduced from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Random coefficient regression analyses focused on during-treatment changes in ASE, with BSI 18 scores and MDD diagnosis included as moderators. At intake, individuals with MDD or high levels of depressive symptoms had significantly lower ASE, particularly in negative affect situations. No evidence for moderation was found: ASE significantly increased during treatment regardless of MDD status. There was a main effect of BSI 18 Depression scores: those with lower BSI 18 scores had lower ASE scores at each time point. MDD and BSI 18 Depression did not predict 3-month outcome, but similar to previous findings ASE did predict abstinence status at 3 months. Treatment-seeking emerging adults with MDD merit particular clinical attention because of their lower reported self-efficacy throughout treatment.     

Mindfulness-based cognitive therapy improves emotional reactivity to social stress: results from a randomized controlled trial

The high likelihood of recurrence in depression is linked to a progressive increase in emotional reactivity to stress (stress sensitization). Mindfulness-based therapies teach mindfulness skills designed to decrease emotional reactivity in the face of negative affect-producing stressors. The primary aim of the current study was to assess whether Mindfulness-Based Cognitive Therapy (MBCT) is efficacious in reducing emotional reactivity to social evaluative threat in a clinical sample with recurrent depression. A secondary aim was to assess whether improvement in emotional reactivity mediates improvements in depressive symptoms. Fifty-two individuals with partially remitted depression were randomized into an 8-week MBCT course or a waitlist control condition. All participants underwent the Trier Social Stress Test (TSST) before and after the 8-week trial period. Emotional reactivity to stress was assessed with the Spielberger State Anxiety Inventory at several time points before, during, and after the stressor. MBCT was associated with decreased emotional reactivity to social stress, specifically during the recovery (post-stressor) phase of the TSST. Waitlist controls showed an increase in anticipatory (pre-stressor) anxiety that was absent in the MBCT group. Improvements in emotional reactivity partially mediated improvements in depressive symptoms. Limitations include small sample size, lack of objective or treatment adherence measures, and non-generalizability to more severely depressed populations. Given that emotional reactivity to stress is an important psychopathological process underlying the chronic and recurrent nature of depression, these findings suggest that mindfulness skills are important in adaptive emotion regulation when coping with stress.     

Centering prayer as an alternative to mindfulness-based cognitive therapy for depression relapse prevention

In the last two decades, mindfulness has made a significant impact on Western secular psychology, as evidenced by several new treatment approaches that utilize mindfulness practices to ameliorate mental illness. Based on Buddhist teachings, mindfulness offers individuals the ability to, among other things, decenter from their thoughts and live in the present moment. As an example, mindfulness-based cognitive therapy (MBCT) teaches decentering and mindfulness techniques to adults in an eight-session group therapy format so as to reduce the likelihood of depression relapse. Yet, some Christian adults may prefer to turn to their own religious heritage, rather than the Buddhist tradition, in order to stave off depression relapse. Thus, the purpose of this article is to present centering prayer, a form of Christian meditation that is rooted in Catholic mysticism, as an alternative treatment for preventing depression relapse in adults. I argue that centering prayer overlaps considerably with MBCT, which makes it a suitable treatment alternative for many Christians in remission from depressive episodes.     

Mindfulness-based cognitive therapy for the treatment of current depressive symptoms: a meta-analysis

ABSTRACT

Mindfulness-based cognitive therapy (MBCT) appears to be a promising intervention for the prevention of relapse in major depressive disorder, but its efficacy in patients with current depressive symptoms is less clear. Randomized clinical trials of MBCT for adult patients with current depressive symptoms were included (k = 13, N = 1046). Comparison conditions were coded based on whether they were intended to be therapeutic (specific active controls) or not (non-specific controls). MBCT was superior to non-specific controls at post-treatment (k = 10, d = 0.71, 95% confidence interval [CI] [0.47, 0.96]), although not at longest follow-up (k = 2, d = 1.47, [?0.71, 3.65], mean follow-up = 5.70 months across all studies with follow-up). MBCT did not differ from other active therapies at post-treatment (k = 6, d = 0.002, [?0.43, 0.44]) and longest follow-up (k = 4, d = 0.26, [?0.24, 0.75]). There was some evidence that studies with higher methodological quality showed smaller effects at post-treatment, but no evidence that effects varied by inclusion criterion. The impact of publication bias appeared minimal. MBCT seems to be efficacious for samples with current depressive symptoms at post-treatment, although a limited number of studies tested the long-term effects of this therapy.     

Predicting recurrence of major depressive disorder in young adults: a prospective study.

Sixty-five young adults with remitted major depressive disorder (MDD) were followed for 18 months. Recurrence of MDD was reported by 41.5% of the initial sample and 49.1% of those who completed the study (n = 53). Survival analyses were used to identify predictors of recurrence so that individuals at greatest risk could be targeted for intervention. Potential predictors included measures of comorbid psychopathology (Axis II pathology, and current and lifetime nonmood Axis I diagnoses), depression-specific clinical features (number of episodes, past treatment, and suicidality), and self-reported cognitive and interpersonal constructs (hope, dysfunctional attitudes, and interpersonal problems). Only personality pathology (specifically, the total dimensional and Cluster B dimensional scores on the International Personality Disorder Examination) significantly predicted hazard of recurrence.     

Treatment preference, engagement, and clinical improvement in pharmacotherapy versus psychotherapy for depression

Pharmacotherapy and psychotherapy are generally effective treatments for major depressive disorder (MDD); however, research suggests that patient preferences may influence outcomes. We examined the effects of treatment preference on attrition, therapeutic alliance, and change in depressive severity in a longitudinal randomized clinical trial comparing pharmacotherapy and psychotherapy. Prior to randomization, 106 individuals with MDD reported whether they preferred psychotherapy, antidepressant medication, or had no preference. A mismatch between preferred and actual treatment was associated with greater likelihood of attrition, fewer expected visits attended, and a less positive working alliance at session 2. There was a significant indirect effect of preference match on depression outcomes, primarily via effects of attendance. These findings highlight the importance of addressing patient preferences, particularly in regard to patient engagement, in the treatment of MDD.