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Background: Mindfulness‐based cognitive therapy (MBCT) is effective in reducing depressive symptoms in patients with major depressive disorder (MDD). Understanding for whom and how MBCT works may allow for improvements in treatment allocation and effectiveness. In this study, our aim was to investigate depressive rumination, content‐independent perseverative thinking, mindfulness skills, and self‐compassion as potential moderators and mediators of MBCT. Methods: In this non‐randomized controlled trial, patients with persistent (n = 53) or recurrent MDD with (n = 31) or without (n = 51) a current depressive episode were assigned to an intervention (MBCT plus treatment as usual [TAU], n = 94) or control group (TAU only, n = 40) based on the time between the date of inclusion and the start of MBCT. Assessments were carried out before, halfway, and after 8 weeks of MBCT + TAU or TAU. Latent growth models were employed to examine moderation, while cross‐lagged structural equation models were used to assess the mediating effects of several possible mediators of MBCT‐induced change in depressive symptoms and overall functional impairment. Results: MBCT + TAU was more effective in reducing depressive symptoms (and overall functional impairment than TAU with a medium [d = −0.54] and small [d = 0.44] effect size, respectively). Higher baseline levels of rumination and perseverative thinking and lower levels of self‐compassion moderated the effect of MBCT on depressive symptoms and overall functional impairment. Task‐based negative intrusive thoughts moderated the effects of MBCT on overall functional impairment. No mediators were established, particularly due to a lack of effect of MBCT on all assessed mediators at mid‐treatment. For interpretative purposes, a sample split (based on Johnson–Newman values) showed moderate‐to‐large effects in depressive symptom reduction for those with high rumination, high perseverative thinking, and low self‐compassion, while negative‐to‐small nonsignificant effects were found for the opposite traits. Conclusion: In the future, MBCT allocation based on levels of rumination and self‐compassion might lead to a more efficient reduction in depressive symptoms. Directions for mediation analysis within the context of MBCT for depression are discussed. Preregistration: This study was initially preregistered in the Dutch National Trial Register (NL7842). However, due to the NTR no longer being available since June 2022, the trial was reregistered at ClinicalTrials.gov (NCT05802966, dd 09‐Apr‐2023). The statistical analysis plan was adjusted after the start of the trial but before the finalization of data collection (NCT05802966; ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Interaction between Pavlovian and instrumental control systems is key for adaptive motivated behavior, but also plays an important role in various neuropsychiatric disorders, including depression, addiction, and anxiety. Here, we employed the flouorodopa positron emission tomography ([18F]-DOPA PET) in healthy participants (N = 100) to assess whether dopamine synthesis capacity (Ki), specifically in the ventral striatum, accounts for individual variation in Pavlovian-to-instrumental transfer (PIT). Surprisingly, this was not the case. Rather, the relationship of ventral striatal Ki with PIT depended on working memory (WM) capacity. Ventral striatal dopamine boosted the effects of Pavlovian cues on instrumental responding to a greater degree in participants with higher WM capacity. Caution is warranted to interpret this post hoc four-way interaction given the modest sample size. Nonetheless, these results chime with prior findings demonstrating that dopaminergic drugs boost Pavlovian biases to a greater degree in participants with greaterWMcapacity and highlight the importance of interactions between striatal dopamine and WM capacity. [ABSTRACT FROM AUTHOR]

Criminal behaviour poses a big challenge for society. A thorough understanding of the neurobiological mechanisms underlying criminality could optimize its prevention and management. Specifically, elucidating the neural mechanisms underpinning reward expectation might be pivotal to understanding criminal behaviour. So far no study has assessed reward expectation and its mechanisms in a criminal sample. To fill this gap, we assessed reward expectation in incarcerated, psychopathic criminals. We compared this group to two groups of non-criminal individuals: one with high levels and another with low levels of impulsive/antisocial traits. Functional magnetic resonance imaging was used to quantify neural responses to reward expectancy. Psychophysiological interaction analyses were performed to examine differences in functional connectivity patterns of reward-related regions. The data suggest that overt criminality is characterized, not by abnormal reward expectation per se, but rather by enhanced communication between reward-related striatal regions and frontal brain regions. We establish that incarcerated psychopathic criminals can be dissociated from non-criminal individuals with comparable impulsive/antisocial personality tendencies based on the degree to which reward-related brain regions interact with brain regions that control behaviour. The present results help us understand why some people act according to their impulsive/antisocial personality while others are able to behave adaptively despite reward-related urges. [ABSTRACT FROM AUTHOR]

Background: Chronic fatigue syndrome (CFS) is characterized by profound and disabling fatigue with no known somatic explanation. Cognitive behavioral therapy (CBT) has proven to be a successful intervention leading to a reduction in fatigue and disability. Based on previous neuroimaging findings, it has been suggested that central neural mechanisms may underlie CFS symptoms and play a role in the change brought on by CBT. In this randomized controlled trial we aim to further investigate the neural mechanisms that underlie fatigue in CFS and their change by CBT. Methods/Design: We will conduct a randomized controlled trial in which we collect anatomical and functional magnetic resonance imaging (MRI) measures from female CFS patients before and after CBT (N = 60) or waiting list (N = 30) and compare these with measures from age and education matched healthy controls (N = 30). By including a large treatment group we will also be able to compare patients that benefit from CBT with those that do not. In addition, to further investigate the role of endocrine and immune biomarkers in CFS, we will determine cortisol and cytokine concentrations in blood, hair and/or saliva. Discussion: This project creates an unique opportunity to enhance our understanding of CFS symptoms and its change by CBT in terms of neuroanatomical, neurofunctional, endocrinological and immunological mechanisms and can help to further improve future treatments strategies. [ABSTRACT FROM AUTHOR]

Adaptive decision-making involves interaction between systems regulating Pavlovian and instrumental control of behavior. Here we investigate in humans the role of serotonin in such Pavlovian-instrumental transfer in both the aversive and the appetitive domain using acute tryptophan depletion, known to lower central serotonin levels. Acute tryptophan depletion attenuated the inhibiting effect of aversive Pavlovian cues on instrumental behavior, while leaving unaltered the activating effect of appetitive Pavlovian cues. These data suggest that serotonin is selectively involved in Pavlovian inhibition due to aversive expectations and have implications for our under-standing of the mechanisms underlying a range of affective, impulsive, and aggressive neuropsychiatrie disorders. [ABSTRACT FROM AUTHOR]

Negative self-referential processing has fruitfully been studied in unipolar depressed patients, but remarkably less in patients with bipolar disorder (BD). This exploratory study examines the relation between task-based self-referential processing and depressive symptoms in BD and their possible importance to the working mechanism of mindfulness-based cognitive therapy (MBCT) for BD. The study population consisted of a subsample of patients with BD ( n  = 49) participating in an RCT of MBCT for BD, who were assigned to MBCT + TAU ( n  = 23) or treatment as usual (TAU) ( n  = 26). Patients performed the self-referential encoding task (SRET), which measures (1) positive and (2) negative attributions to oneself as well as (3) negative self-referential memory bias, before and after MBCT + TAU or TAU. At baseline, all three SRET measures were significantly related to depressive symptoms in patients with BD. Moreover, repeated measures analyses of variance revealed that negative self-referential memory bias diminished over time in the MBCT + TAU group, compared with the TAU group. Given the preliminary nature of our findings, future research should explore the possibly mediating role of reducing negative self-referential memory bias in preventing and treating depressive symptoms in BD through MBCT.

Background: Over the past two decades there has been a growing number of randomized clinical trials supporting the efficacy of mindfulness-based cognitive therapy (MBCT) in the treatment of several psychiatric disorders. Since evidence for its effectiveness in routine clinical practice is lagging behind, we aimed to examine adherence, outcome and predictors of MBCT in a well-characterized, heterogeneous outpatient population in routine clinical practice., Methods: Data were collected from a naturalistic uncontrolled cohort of 998 patients formally diagnosed with mainly depression, anxiety disorders, personality disorders, somatoform disorders and/or ADHD. Patients received protocolized MBCT and completed self-report questionnaires pre- and post-treatment on overall functioning (Outcome Questionnaire, primary outcome), depressive symptoms, worry, mindfulness skills and self-compassion. Pre-to post-treatment changes were analysed for the overall sample and each diagnostic category separately with paired sample t-tests, reliable change indices (only overall sample) and repeated measures ANOVA for groups with and without comorbidity. Multiple linear regression was carried out to assess possible predictors of adherence and change in overall functioning., Results: Adherence was high (94%) but negatively affected by lower levels of education, more comorbidity and presence of ADHD. Outcome in terms of improvement in overall functioning was good in the overall sample (Cohen's d = 0.50, 30% showed reliable improvement vs. 3.5% reliable deterioration) and within each diagnostic category (Cohen's d range = 0.37-0.61). Worse overall functioning at baseline was the only predictor for a larger treatment effect., Conclusions: After MBCT, overall functioning improved in a large heterogeneous psychiatric outpatient population independent of diagnosis or comorbidity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Mindfulness-based cognitive therapy (MBCT) has been demonstrated to be effective in adults with ADHD. The aim of the current study was to examine its possible working mechanisms. Method: In the context of an randomized controlled trial (RCT), MBCT + TAU (treatment as usual) ( n = 43) versus TAU ( n = 51), we used mediation analyses to examine whether reduction of clinician-rated ADHD symptoms and improvement of positive mental health at 6-month follow-up had been mediated by change in mindfulness skills, self-compassion, and executive functioning over the course of MBCT. Results: Increase of self-compassion mediated improvement of positive mental health at 6-month follow-up. Improvement of mindfulness skills or self-compassion did not mediate the reduction in ADHD symptoms. Additional analyses suggest that self-reported inhibition did. Conclusion: The effect of MBCT on ADHD symptoms and positive mental health thus occurred via different mechanisms of change, that is, by improvements in inhibition and self-compassion, respectively.

Background: Meta-analyses show efficacy of mindfulness-based cognitive therapy (MBCT) in terms of relapse prevention and depressive symptom reduction in patients with major depressive disorder (MDD). However, most studies have been conducted in controlled research settings., Aims: We aimed to investigate the effectiveness of MBCT in patients with MDD presenting in real-world clinical practice. Moreover, we assessed whether guideline recommendations for MBCT allocation in regard to recurrence and remission status of MDD hold in clinical practice., Method: This study assessed a naturalistic cohort of patients with (recurrent) MDD, either current or in remission (n = 765), who received MBCT in a university hospital out-patient clinic in The Netherlands. Outcome measures were self-reported depressive symptoms, worry, mindfulness skills and self-compassion. Predictors were MDD recurrence and remission status, and clinical and sociodemographic variables. Outcome and predictor analyses were conducted with linear regression., Results: MBCT adherence was high (94%). Patients with a lower level of education had a higher chance of non-adherence. Attending more sessions positively influenced improvement in depressive symptoms. Depressive symptoms significantly reduced from pre- to post-MBCT (Δ mean = 7.7, 95%CI = 7.0-8.5, Cohen's d = 0.75). Improvement of depressive symptoms was independent from MDD recurrence and remission status. Unemployed patients showed less favourable outcomes. Worry, mindfulness skills and self-compassion all significantly improved. These improvements were related to changes in depressive symptoms., Conclusions: Previous efficacy results in controlled research settings are maintained in clinical practice. Results illustrate that MBCT is effective in routine clinical practice for patients suffering from MDD, irrespective of MDD recurrence and remission status.

Background: Chronic fatigue syndrome (CFS) is characterized by disabling fatigue, which is suggested to be maintained by dysfunctional beliefs. Fatigue and its maintenance are recently conceptualized as arising from abnormally precise expectations about bodily inputs and from beliefs of diminished control over bodily states, respectively. This study used functional neuroimaging to identify the neural correlates of fatigue and its maintenance by beliefs during a physical effort task., Methods: We isolated behavioral adjustments and cerebral activity during feedback processing and motor preparation, in the context of a task in which patients with CFS (n = 85) and healthy control subjects (n = 29) produced 30%, 50%, and 70% of their right-hand maximal voluntary contraction, and received directional feedback on performance (e.g., too little force)., Results: Patients with CSF showed an effort-dependent behavioral bias toward less effort investment in response to directional feedback for the highest effort level as compared with healthy control subjects. This bias was associated with reduced feedback-related activity in the dorsolateral prefrontal cortex. These effects were proportional to state-related fatigue and prior beliefs about CFS patients' ability to perform the task. Patients with CFS also showed higher activity in the supplementary motor area, proportional to their state-related fatigue, and reduced connectivity between the supplementary motor area and sensorimotor cortex during motor preparation as compared with control subjects., Conclusions: These findings link fatigue symptoms to alterations in behavioral choices on effort investment, prefrontal functioning, and supplementary motor area connectivity, with the dorsolateral prefrontal cortex being associated with prior beliefs about physical abilities., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity)., Methods: We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls., Results: The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups., Conclusions: CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Drugs that alter dopamine transmission have opposite effects on reward and punishment learning. These opposite effects have been suggested to depend on dopamine in the striatum. Here, we establish for the first time the neurochemical specificity of such drug effects, during reward and punishment learning in humans, by adopting a coadministration design. Participants (N = 22) were scanned on 4 occasions using functional magnetic resonance imaging, following intake of placebo, bromocriptine (dopamine-receptor agonist), sulpiride (dopamine-receptor antagonist), or a combination of both drugs. A reversal-learning task was employed, in which both unexpected rewards and punishments signaled reversals. Drug effects were stratified with baseline working memory to take into account individual variations in drug response. Sulpiride induced parallel span-dependent changes on striatal blood oxygen level-dependent (BOLD) signal during unexpected rewards and punishments. These drug effects were found to be partially dopamine-dependent, as they were blocked by coadministration with bromocriptine. In contrast, sulpiride elicited opposite effects on behavioral measures of reward and punishment learning. Moreover, sulpiride-induced increases in striatal BOLD signal during both outcomes were associated with behavioral improvement in reward versus punishment learning. These results provide a strong support for current theories, suggesting that drug effects on reward and punishment learning are mediated via striatal dopamine.