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.

Cognitive predictors of stress-induced mood malleability in depression.

BACKGROUND & OBJECTIVES: Basic attentional control, negative biases in attention and interpretation, and rumination are all cognitive processes associated with depression; however, less is known about their predictive role in depressive mood reactivity and -recovery in response to stress, and their relation to severity of depression. DESIGN & METHODS: We experimentally induced stress based on an autobiographical imagery script in a sample of 92 participants with Major Depressive Disorder with or without comorbid anxiety disorders. We used simple regression analysis for investigating the roles of state- and trait rumination, attentional networks, and attentional and interpretation biases for predicting stress-induced depressive mood reactivity and -recovery, respectively, and whether they in parallel mediated the association between cognitive processes and depression severity. RESULTS: Stress-induced depressive mood reactivity was predicted by better orienting ability and more state rumination. Better recovery was predicted by better orienting efficiency and lower negative interpretation bias. Furthermore, the relation between state rumination and depression severity was partially mediated by depressive mood reactivity, however limited by the lack of temporal precedence in the analysis. CONCLUSIONS: We characterized the relation between cognitive processes and mood malleability in response to stress. Findings could refine theoretical models of depression if causality is established. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04137367.

The effect of emotion recognition and mindfulness on depression symptoms: A case-control study.

Abnormalities in emotion recognition (ER) are frequently reported in depression, with lower recognition accuracy in patients with major depressive disorder (MDD) when compared to healthy individuals. Mindfulness was found to directly impact the severity of depressive symptoms, by recognizing negative cognitions and dysfunctional reactions. The aims of this study were to compare ER and mindfulness levels between MDD patients and healthy controls (HCs), as well as to examine whether ER and mindfulness are related to symptom severity in MDD patients. Sixty-eight patients with MDD and 93 HCs participated in the study. A sociodemographic form, reading the mind in the eyes test (RMET), five facet mindfulness questionnaire-short form (FFMQ-S) and the Montgomery-Asberg depression scale (MADRS) were administered. Group comparison in ER and mindfulness was performed using the multivariate analysis of covariance (MANCOVA). Bivariate correlations and hierarchical linear regression analyses were performed to assess the associations between depression severity, ER and mindfulness in the patient group. Higher level of mindfulness was found in HCs relative to MDD group, however, no ER difference was present between the groups. A positive association between depression severity and the non-reactivity facet of mindfulness was found. On the other hand, ER was not significantly associated with symptom severity among individuals with MDD. Non-reactivity, unlike other dimensions of mindfulness, seems to increase with the severity of depressive symptoms among MDD patients. A particular focus on this subdimension in mindfulness techniques may yield better outcomes in alleviation of depressive symptoms.

Machine Learning Prediction of Quality of Life Improvement During Antidepressant Treatment of Patients With Major Depressive Disorder: A STAR*D and CAN-BIND-1 Report.

Background: Quality of life (QoL) is an important patient-centric outcome to evaluate in treatment of major depressive disorder (MDD). This work sought to investigate the performance of several machine learning methods to predict a return to normative QoL in patients with MDD after antidepressant treatment.Methods: Several binary classification algorithms were trained on data from the first 2 weeks of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (n = 651, conducted from 2001 to 2006) to predict week 9 normative QoL (score ≥ 67, based on a community normative sample, on the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form [Q-LES-Q-SF]) after treatment with citalopram. Internal validation was performed using a STAR*D holdout dataset, and external validation was performed using the Canadian Biomarker Integration Network in Depression-1 (CAN-BIND-1) dataset (n = 175, study conducted from 2012 to 2017) after treatment with escitalopram. Feature importance was calculated using SHapley Additive exPlanations (SHAP).Results: Random Forest performed most consistently on internal and external validation, with balanced accuracy (area under the receiver operator curve) of 71% (0.81) on the STAR*D dataset and 69% (0.75) on the CAN-BIND-1 dataset. Random Forest Classifiers trained on Q-LES-Q-SF and Quick Inventory of Depressive Symptomatology-Self-Rated variables had similar performance on both internal and external validation. Important predictive variables came from psychological, physical, and socioeconomic domains.Conclusions: Machine learning can predict normative QoL after antidepressant treatment with similar performance to that of prior work predicting depressive symptom response and remission. These results suggest that QoL outcomes in MDD patients can be predicted with simple patient-rated measures and provide a foundation to further improve performance and demonstrate clinical utility.Trial Registration: ClinicalTrials.gov identifiers NCT00021528 and NCT01655706.

Efficacy of an Electronic Cognitive Behavioral Therapy Program Delivered via the Online Psychotherapy Tool for Depression and Anxiety Related to the COVID-19 Pandemic: Pre-Post Pilot Study.

BACKGROUND: Lockdowns and social distancing resulting from the COVID-19 pandemic have worsened the population's mental health and made it more difficult for individuals to receive care. Electronic cognitive behavioral therapy (e-CBT) is a cost-effective and evidence-based treatment for anxiety and depression and can be accessed remotely. OBJECTIVE: The objective of the study was to investigate the efficacy of online psychotherapy tailored to depression and anxiety symptoms during the pandemic. METHODS: The pilot study used a pre-post design to evaluate the efficacy of a 9-week e-CBT program designed for individuals with depression and anxiety affected by the pandemic. Participants were adults (N=59) diagnosed with major depressive disorder and generalized anxiety disorder, whose mental health symptoms initiated or worsened during the COVID-19 pandemic. The online psychotherapy program focused on teaching coping, mindfulness, and problem-solving skills. Symptoms of anxiety and depression, resilience, and quality of life were assessed. RESULTS: Participants demonstrated significant improvements in symptoms of anxiety (P=.02) and depression (P=.03) after the intervention. Similar trends were observed in the intention-to-treat analysis. No significant differences were observed in resilience and quality-of-life measures. The sample comprised mostly females, making it challenging to discern the benefits of the intervention in males. Although a pre-post design is less rigorous than a controlled trial, this design was selected to observe changes in scores during a critical period. CONCLUSIONS: e-CBT for COVID-19 is an effective and accessible treatment option. Improvements in clinical symptoms of anxiety and depression can be observed in individuals whose mental health is affected by the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT04476667; https://clinicaltrials.gov/study/NCT04476667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/24913.

Macroscopic resting state model predicts theta burst stimulation response: A randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner. Computational modelling combined with probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil. We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony. Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.

The influence of childhood maltreatment on trait depression in patients with major depressive disorder: A moderated mediation model of rumination and mindful attention awareness.

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Individuals who were exposed to childhood maltreatment might be an especially vulnerable group and were more likely to meet the diagnostic criteria for depression than those who were not. Trait depression refers to a personality trait predisposition to depression, expressed as the frequency of symptoms rather than a transient depressive mood state. Clarifying the relationship between childhood maltreatment and trait depression in patients with MDD has therefore become an important field of research. Childhood Trauma Questionnaire-Short Form (CTQ-SF), Ruminative Responses Scale (RRS), State-Trait Depression Scale (ST-DEP), and Mindful Attention Awareness Scale (MAAS) were used as research instruments. SPSS 23.0 statistical software was used for statistical analysis and examined the moderated mediation models. A total of 288 patients with MDD were included in this study. After standardization of the variables, the model revealed childhood maltreatment was positively associated with trait depression (ß = 0.215, p < 0.001) and that rumination partially mediated the effect between childhood trauma and trait depression. Mindfulness moderated the association between rumination and trait depression in depressed patients (ß = 0.171, p < 0.001). Simple slope tests showed that rumination significantly predicted trait depression in patients with high levels of mindfulness (bsimple = 0.460, p < 0.001, 95%CI = [0.339, 0.581]), while this predictive effect was not significant in patients with low levels (bsimple = 0.119, p = 0.097, 95%CI = [-0.022, 0.261]). After adding mediating variables, we found that the negative impact of childhood maltreatment on trait depression was both directly and indirectly through the patients' own ruminative levels. However, mindfulness performed a critical moderating role in the overall mediating model, aggravating the negative impact of childhood maltreatment on trait depression. There are several limitations in this study: the history of childhood maltreatment was reviewed and reported; the MAAS was a single-dimensional questionnaire that fails to measure the content of other mindfulness factors; cross-sectional data could not be used to infer the causal relationship between variables.

Comprehensive mental health and psychosocial support for war survivors at Chenna Kebele, Dabat woreda, North Gondar, Ethiopia.

BACKGROUND: Armed conflict and natural disasters cause serious psychosocial problems. Providing comprehensive bio-psychosocial support to the community after a war, traumatic, or devastating event has a significant impact on community reconstruction and resilience. As a result, the goal of this project was to conduct community diagnosis, identify individuals experiencing psychological distress, and provide comprehensive mental health and psychosocial support for the Chenna Kebele population in Dabat Woreda, North Gondar, Ethiopia. METHODS: A mixed research approach, specifically an explanatory study design, was used to assess psychosocial issues among war survivors. In-depth interviews, focus group discussions, and observation were used to assess the psychosocial and economic consequences of the war on survivors. Additionally, a structured questionnaire was employed to assess mental health problems among the target population. The project was conducted in three phases. RESULT: A total of 550 households were assessed using a structured questionnaire. Of them, 45 people reported a range of mental health issues, including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), adjustment disorder, protracted bereavement disorder, and insomnia. PTSD is the most common diagnosis, accounting for 38 cases. Four cases of major depressive disorder, three cases of prolonged grief, and two neurologic cases were also identified during the screening. Females had a higher number of PTSD cases as compared with males. Fifteen women reported sexual violence, and the number may be high because of underreporting and refusal to disclose the situation. The result also indicated significant property damage, loss of life stocks, and disengagement from basic services like water. Intervention with follow-up was provided at the individual, group, and community levels in order to reverse the devastating situation. The intervention included pharmacotherapy, psychotherapy, and social networking. CONCLUSION AND RECOMMENDATION: Overall, the community has experienced multiple psychosocial and economic problems. Hence, providing holistic mental health psychosocial support, clearing the site and burying the dead body, and re-initiating the terminated social gathering event will alleviate the existing problem and create a resilient community.

Zuranolone and its role in treating major depressive disorder: a narrative review.

Major Depressive Disorder (MDD) is a mood disorder classified as a persistent depressive mood and loss of interest lasting for more than two weeks and accompanied by a list of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria. MDD affects approximately 264 million people worldwide and is the most prevailing form of neuropsychiatric disorder. Owing to the probable hypothesized pathophysiology of MDD being an outcome of abnormalities in the amino acid neurotransmitter system, including glutamate (the primary excitatory neurotransmitter) and γ-aminobutyric acid (GABA), SAGE-217 (Zuranolone) is being evaluated as a possible therapeutic treatment for MDD. Zuranolone is a synthetic, neuroactive steroid (NAS) and positive allosteric modulator (PMA) of GABAA receptors, regulating both synaptic and extra-synaptic release of GABA. It is administered as a once-daily oral dose for 2 weeks due to its low-moderate clearance. A change in total HAM-D score from baseline was the primary end-point of all the trials. A phase II trial conducted to evaluate the efficacy and safety of Zuranolone (30 mg, once-daily dose), described a significant reduction in total HAM-D score at day 14 and reported the drug to be well tolerated with headache, dizziness, nausea, and somnolence as the most common adverse events (AE). Additional phase III trials were also conducted to evaluate similar outcomes, the interim topline results of which have been released. Consequently, this article attempts to briefly analyze the pharmacology of Zuranolone, review the available clinical data and outcomes regarding its use, and evaluate its place as a prospective novel therapy in the effective management of MDD.

Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial.

BACKGROUND: Randomised sham-controlled trials of cranial electrostimulation with the Alpha-Stim Anxiety Insomnia and Depression (AID) device have reported improved anxiety and depression symptoms; however, no adequately powered sham-controlled trials in major depression are available. We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression. METHODS: The Alpha-Stim-D trial was a multicentre, parallel group, double-blind, randomised controlled trial, recruiting participants from 25 primary care centres in two regions in England, UK. Eligible participants were aged 16 years or older with a current diagnosis of primary major depression, a score of 10-19 on the nine-item Patient Health Questionnaire, and had been offered or prescribed and reported taking antidepressant medication for at least 6 weeks in the previous 3 months. Main exclusion criteria were contraindications to Alpha-Stim AID device use, having persistent suicidal ideation or self-harm, neurological conditions, a substance use disorder or dependence, an eating disorder, bipolar disorder, or non-affective psychosis, or receiving psychological treatment in the past 3 months. Eligible participants were randomly assigned (1:1, minimised by region, anxiety disorder, and antidepressant use) to 1 h daily use of active (100 µA) or sham Alpha-Stim AID treatment for 8 weeks. Randomisation was via an independent web-based system, with participants, outcome assessors, and data analyst masked to treatment assignment. The primary outcome was change from baseline in score on the 17-item Hamilton Depression Rating Scale (HDRS-17, GRID version) at 16 weeks after randomisation, with participants analysed by intention to treat (ITT; all randomly assigned participants). Safety was assessed in all randomly assigned participants. The trial is registered with the ISRCTN registry (ISRCTN11853110); status completed. FINDINGS: Between Sept 8, 2020, and Jan 14, 2022, 236 eligible participants were randomly assigned to active or sham Alpha-Stim AID (n=118 each). 156 (66%) participants were women, 77 (33%) were men, and three (1%) self-reported as other gender; 200 (85%) were White British or Irish; and the mean age was 38·0 years (SD 15·3; range 16-83). 102 (86%) participants in the active Alpha-Stim AID group and 98 (83%) in the sham group were followed up 16 weeks after randomisation. In the ITT population, mean change in GRID-HDRS-17 at 16 weeks was -5·9 (95% CI -7·1 to -4·8) in the active Alpha-Stim AID group and -6·5 (-7·7 to -5·4) in the sham group (mean change difference -0·6 [95% CI -1·0 to 2·2], p=0·46). Among the 236 participants, 17 adverse events were reported in 17 (7%) participants (nine [8%] participants in the active Alpha-Stim AID group; and eight [7%] participants in the sham group). One serious adverse event of suicidal ideation leading to hospitalisation was reported in the sham group, which was judged to be unrelated to the device. INTERPRETATION: Active Alpha-Stim AID was safe and acceptable, but no more clinically effective than sham Alpha-Stim AID in major depression. FUNDING: National Institute for Health Research Applied Research Collaboration East Midlands and Electromedical Products International.

Design and rationale of the REStoring mood after early life trauma with psychotherapy (RESET-psychotherapy) study: a multicenter randomized controlled trial on the efficacy of adjunctive trauma-focused therapy (TFT) versus treatment as usual (TAU) for adult patients with major depressive disorder (MDD) and childhood trauma.

BACKGROUND: Major depressive disorder (MDD) is a common, recurrent mental disorder and a leading cause of disability worldwide. A large part of adult MDD patients report a history of childhood trauma (CT). Patients with MDD and CT are assumed to represent a clinically and neurobiologically distinct MDD subtype with an earlier onset, unfavorable disease course, stress systems' dysregulations and brain alterations. Currently, there is no evidence-based treatment strategy for MDD that specifically targets CT. Given the central role of trauma in MDD patients with CT, trauma-focused therapy (TFT), adjunctive to treatment as usual (TAU), may be efficacious to alleviate depressive symptoms in this patient population. METHODS: The RESET-psychotherapy study is a 12-week, single-blind, randomized controlled trial testing the efficacy of TFT in 158 adults with moderate to severe MDD, as a 'stand-alone' depression diagnosis or superimposed on a persistent depressive disorder (PDD), and CT. TFT (6-10 sessions of Eye Movement Desensitization and Reprocessing and/or imagery rescripting) + TAU is compared to TAU only. Assessments, including a wide range of psychological/psychiatric and biological characteristics, take place before randomization (T0), during treatment (T1), at post-treatment (T2) and at 6-month follow-up (T3). Pre-post treatment stress-related biomarkers in hair (cortisol) and blood (epigenetics and inflammation) will be assessed to better understand working mechanisms of TFT. A subgroup of 60 participants will undergo structural and functional Magnetic Resonance Imaging (MRI) assessments to determine pre-post treatment brain activity. The primary outcome is self-reported depression symptom severity at post-treatment, measured with the 30-item Inventory of Depressive Symptomatology - Self Report (IDS-SR). DISCUSSION: If adjunctive TFT efficaciously alleviates depressive symptoms in MDD patients with CT, this novel treatment strategy could pave the way for a more personalized and targeted MDD treatment. TRIAL REGISTRATION: ClinicalTrials.gov, registered at 08-12-2021, number of identification: NCT05149352.

Effects of Mindfulness-Based Cognitive Therapy on Major Depressive Disorder with Multiple Episodes: A Systematic Review and Meta-Analysis.

This study synthesizes the effect of mindfulness-based cognitive therapy (MBCT) on depression and suicidal ideation among patients with major depressive disorder (MDD). During treatment, patients with MDD may experience repeated episodes, negative counseling, and suicidal ideation, which can lead to further depression and ultimately affect quality of life. Recent studies have shown that MBCT can improve the level of depression and suicidal ideation in patients with MDD. A systematic review and meta-analysis of randomized controlled trials was conducted. The literature search for articles up to December 2021 was performed in the following electronic databases: Airiti Library, PsycINFO, CINAHL, Cochrane Library, PubMed/MEDLINE, ProQuest, and the Index of the Taiwan Periodical Literature System. Records were independently evaluated by two reviewers. Disagreements were resolved through consensus. The quality of study was evaluated using the Modified Jadad Scale score. A meta-analysis was performed using Review Manager Version 5.3.5 software with a random-effects model. Thirteen studies (1159 participants) investigating MBCT for patients with MDD were included. The MBCT sessions lasted 1.5-2.5 h and were delivered by therapists five times per week for 8 weeks. The meta-effects of MBCT among patients with MDD showed significant improvement in depression and suicidal ideation. Future research should evaluate the long-term effects of MBCT. MBCT is relatively convenient and effective for preventing and alleviating depression and suicidal ideation. Further research can provide detailed suggestions for effective MBCT implementation.

Effect of Acupuncture on Physical Symptoms and Quality of Life in Treatment-Resistant Major Depressive Disorder and Bipolar Disorder: a Single-Arm Longitudinal Study.

Background: Acupuncture is a non-pharmacological therapy used clinically for mood disorders. Relief of physical symptoms with acupuncture treatment may lead to relief of depressive symptoms and improvement of quality of life (QoL). Few studies have examined the effect of acupuncture on the physical symptoms and QoL of patients with mood disorders. Objectives: To examine the effect of acupuncture on physical symptoms and QoL of patients with treatment-resistant major depressive disorder (MDD) and bipolar disorder (BD). Methods: This prospective, single-arm, longitudinal study included patients with MDD and BD from an outpatient psychiatric clinic. Acupuncture was performed weekly for 12 weeks in combination with regular treatment, with fixed acupoints and individualized treatment for each patient. Psychiatric symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS). Physical symptoms such as physical pain, gastrointestinal symptoms, and sleep disorders were evaluated using the Japanese version of the Somatic Symptom Scale-8 (SSS-8) and Visual Analog Scale (VAS). QoL was evaluated using the 8-item Short-Form (SF-8) Health Survey. Results: A total of 36 patients (15 MDD and 21 BD patients) were analyzed. After 12 weeks of acupuncture, HSDS and HSAS scores significantly decreased (p < 0.05). Physical symptoms evaluated using SSS-8 and VAS scores also significantly improved (p < 0.05). In particular, neck pain and insomnia improved at an early stage. Among the SF-8 subscales, scores of bodily pain, general health perception, role limitations due to emotional problems, and mental health significantly increased (p < 0.05). Conclusion: Acupuncture may improve not only psychiatric symptoms but also physical symptoms and QoL in patients with treatment-resistant mood disorders. Further studies are required for confirmation of the preliminary data collected thus far.

Effectiveness of mindfulness-based cognitive therapy against suicidal ideation in patients with depression: A systematic review and meta-analysis.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) can effectively prevent relapse of major depression, but there is currently insufficient evidence for efficacy against suicidal ideation during depressive episodes. We thus conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing MBCT to treatment as usual (TAU) for suppression of suicidal ideation in patients with current depression. METHODS: We systematically searched PubMed, Embase, Cochrane, CNKI, and Wan Fang databases for RCTs published in English or Chinese between January 1, 2000, and August 30, 2021. Pooled data were compared between MBCT and TAU groups using a random-effects model. FINDINGS: Seven RCTs with a total of 479 participants were included. Suicidal ideation and general depression scores were significantly improved following MBCT compared to TAU [Suicidal Ideation: standard mean difference (SMD) = -0.33, 95 % CI, -0.56 to -0.10; Depression: SMD = -0.96, 95%CI, -1.54 to -0.38]. INTERPRETATION: Mindfulness-based cognitive therapy is an effective intervention for reducing depressive symptoms and suicidal ideation in depressed patients. TRIAL REGISTRATION: This meta-analysis was conducted in accordance with PRISMA guidelines and registered at PROSPERO https://www.crd.york.ac.uk/PROSPERO/ (CRD42021285016).

A systematic meta-review of patient-level predictors of psychological therapy outcome in major depressive disorder.

BACKGROUND: Psychological therapies are effective for treating major depressive disorder, but current clinical guidelines do not provide guidance on the personalization of treatment choice. Established predictors of psychotherapy treatment response could help inform machine learning models aimed at predicting individual patient responses to different therapy options. Here we sought to comprehensively identify known predictors. METHODS: EMBASE, Medline, PubMed, PsycINFO were searched for systematic reviews with or without meta-analysis published until June 2020 to identify individual patient-level predictors of response to psychological treatments. 3113 abstracts were identified and 300 articles assessed. We qualitatively synthesized our findings by predictor category (sociodemographic; symptom profile; social support; personality features; affective, cognitive, and behavioural; comorbidities; neuroimaging; genetics) and treatment type. We used the AMSTAR 2 to evaluate the quality of included reviews. RESULTS: Following screening and full-text assessment, 27 systematic reviews including 12 meta-analyses were eligible for inclusion. 74 predictors emerged for various psychological treatments, primarily cognitive behavioural therapy, interpersonal therapy, and mindfulness-based cognitive therapy. LIMITATIONS: A paucity of studies examining predictors of psychological treatment outcome, as well as methodological heterogeneities and publication biases limit the strength of the identified predictors. CONCLUSIONS: The synthesized predictors could be used to supplement clinical decision-making in selecting psychological therapies based on individual patient characteristics. These predictors could also be used as a priori input features for machine learning models aimed at predicting a given patient's likelihood of response to different treatment options for depression, and may contribute toward the development of patient-specific treatment recommendations in clinical guidelines.

Static and treatment-responsive brain biomarkers of depression relapse vulnerability following prophylactic psychotherapy: Evidence from a randomized control trial.

BACKGROUND: Neural reactivity to dysphoric mood induction indexes the tendency for distress to promote cognitive reactivity and sensory avoidance. Linking these responses to illness prognosis following recovery from Major Depressive Disorder informs our understanding of depression vulnerability and provides engagement targets for prophylactic interventions. METHODS: A prospective fMRI neuroimaging design investigated the relationship between dysphoric reactivity and relapse following prophylactic intervention. Remitted depressed outpatients (N = 85) were randomized to 8 weeks of Cognitive Therapy with a Well-Being focus or Mindfulness Based Cognitive Therapy. Participants were assessed before and after therapy and followed for 2 years to assess relapse status. Neural reactivity common to both assessment points identified static biomarkers of relapse, whereas reactivity change identified dynamic biomarkers. RESULTS: Dysphoric mood induction evoked prefrontal activation and sensory deactivation. Controlling for past episodes, concurrent symptoms and medication status, somatosensory deactivation was associated with depression recurrence in a static pattern that was unaffected by prophylactic treatment, HR 0.04, 95% CI [0.01, 0.14], p < .001. Treatment-related prophylaxis was linked to reduced activation of the left lateral prefrontal cortex (LPFC), HR 3.73, 95% CI [1.33, 10.46], p = .013. Contralaterally, the right LPFC showed dysphoria-evoked inhibitory connectivity with the right somatosensory biomarker CONCLUSIONS: These findings support a two-factor model of depression relapse vulnerability, in which: enduring patterns of dysphoria-evoked sensory deactivation contribute to episode return, but vulnerability may be mitigated by targeting prefrontal regions responsive to clinical intervention. Emotion regulation during illness remission may be enhanced by reducing prefrontal cognitive processes in favor of sensory representation and integration.

Association between decentering and reductions in relapse/recurrence in mindfulness-based cognitive therapy for depression in adults: A randomized controlled trial.

OBJECTIVE: "Decentering" is defined as the ability to observe one's thoughts and feelings as temporary, objective events in the mind (Safran & Segal, 1990), and is increasingly regarded as a candidate mechanism in mindfulness-based interventions. The present study sought to examine the role of decentering, and other related variables, in the efficacy of Mindfulness-based cognitive therapy (MBCT) as compared to two active comparison conditions. METHOD: Formerly depressed individuals (N = 227), randomly assigned to MBCT (n = 74), relaxation group therapy (RGT; n = 77) or Treatment as usual (TAU; n = 76), completed self-report measures of decentering and symptoms of depression at pre-, mid-, and posttreatment, and relapse was assessed at 3, 6, 9, and 12 months, posttreatment. RESULTS: With regard to the acute treatment phase, results indicated that, whereas levels of depression increased in both RGT and TAU, MBCT patients remained free from symptom gains. Moreover, gains in decentering from mid- to posttreatment predicted reductions in depression from pre- to posttreatment for MBCT and TAU, but not for RGT. Participants who experienced increases in decentering, measured from mid- to posttreatment, generally evidenced the lowest levels of relapse/recurrence (during the four follow-up assessments), largely irrespective of treatment group. However, results related to change in decentering should be considered exploratory due to small cell sizes among participants who did not experience gains in decentering. CONCLUSIONS: Taken together, these results suggest that decentering is a potent mechanism for reduction of relapse in major depression, albeit one that is nonspecific to MBCT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Autobiographical memory style and clinical outcomes following mindfulness-based cognitive therapy (MBCT): An individual patient data meta-analysis.

The ability to retrieve specific, single-incident autobiographical memories has been consistently posited as a predictor of recurrent depression. Elucidating the role of autobiographical memory specificity in patient-response to depressive treatments may improve treatment efficacy and facilitate use of science-driven interventions. We used recent methodological advances in individual patient data meta-analysis to determine a) whether memory specificity is improved following mindfulness-based cognitive therapy (MBCT), relative to control interventions, and b) whether pre-treatment memory specificity moderates treatment response. All bar one study evaluated MBCT for relapse prevention for depression. Our initial analysis therefore focussed on MBCT datasets only(n = 708), then were repeated including the additional dataset(n = 880). Memory specificity did not significantly differ from baseline to post-treatment for either MBCT and Control interventions. There was no evidence that baseline memory specificity predicted treatment response in terms of symptom-levels, or risk of relapse. Findings raise important questions regarding the role of memory specificity in depressive treatments.

Self-compassion and related factors in severe mental illness: A scoping review.

PURPOSE: To clarify what is known and identify research gaps on the role of self-compassion (SC) and potential interventions for individuals with severe mental illness (SMI). DESIGN AND METHODS: We analyzed 24 studies of SC in schizophrenia spectrum disorder, bipolar disorder (BD), and major depressive disorder (MDD). FINDINGS: Mindfulness-based cognitive therapy (MBCT) was the most common intervention. Predicting depression by SC was common in MDD and BD; however, relationships between demographics/clinical variables and SC in BD and schizophrenia spectrum disorder remain unclear. PRACTICE IMPLICATIONS: MBCT increases SC in SMI. Data regarding predictors of SC are limited, especially in schizophrenia.