Mindfulness based cognitive therapy (MBCT) reduces depression-related self-referential processing in patients with bipolar disorder: an exploratory task-based study.

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.

Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.

Establishing the dopamine dependency of human striatal signals during reward and punishment reversal learning.

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.

Investigating neural mechanisms of change of cognitive behavioural therapy for chronic fatigue syndrome: a randomized controlled trial.

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. TRIAL REGISTRATION: Dutch Trial Register #15852. Registered 9 December 2013 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4311 ).

Serotonin and aversive Pavlovian control of instrumental behavior in humans.

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 understanding of the mechanisms underlying a range of affective, impulsive, and aggressive neuropsychiatric disorders.

Aversive Pavlovian control of instrumental behavior in humans.

Adaptive behavior involves interactions between systems regulating Pavlovian and instrumental control of actions. Here, we present the first investigation of the neural mechanisms underlying aversive Pavlovian-instrumental transfer using fMRI in humans. Recent evidence indicates that these Pavlovian influences on instrumental actions are action-specific: Instrumental approach is invigorated by appetitive Pavlovian cues but inhibited by aversive Pavlovian cues. Conversely, instrumental withdrawal is inhibited by appetitive Pavlovian cues but invigorated by aversive Pavlovian cues. We show that BOLD responses in the amygdala and the nucleus accumbens were associated with behavioral inhibition by aversive Pavlovian cues, irrespective of action context. Furthermore, BOLD responses in the ventromedial prefrontal cortex differed between approach and withdrawal actions. Aversive Pavlovian conditioned stimuli modulated connectivity between the ventromedial prefrontal cortex and the caudate nucleus. These results show that action-specific aversive control of instrumental behavior involves the modulation of fronto-striatal interactions by Pavlovian conditioned stimuli.

Study protocol for a randomised controlled trial investigating the effects of Mindfulness Based Stress Reduction on stress regulation and associated neurocognitive mechanisms in stressed university students: the MindRest study.

BACKGROUND: Stress-related disorders are a growing public health concern. While stress is a natural and adaptive process, chronic exposure to stressors can lead to dysregulation and take a cumulative toll on physical and mental well-being. One approach to coping with stress and building resilience is through Mindfulness-Based Stress Reduction (MBSR). By understanding the neural mechanisms of MBSR, we can gain insight into how it reduces stress and what drives individual differences in treatment outcomes. This study aims to establish the clinical effects of MBSR on stress regulation in a population that is susceptible to develop stress-related disorders (i.e., university students with mild to high self-reported stress), to assess the role of large-scale brain networks in stress regulation changes induced by MBSR, and to identify who may benefit most from MBSR. METHODS: This study is a longitudinal two-arm randomised, wait-list controlled trial to investigate the effects of MBSR on a preselected, Dutch university student population with elevated stress levels. Clinical symptoms are measured at baseline, post-treatment, and three months after training. Our primary clinical symptom is perceived stress, with additional measures of depressive and anxiety symptoms, alcohol use, stress resilience, positive mental health, and stress reactivity in daily life. We investigate the effects of MBSR on stress regulation in terms of behaviour, self-report measures, physiology, and brain activity. Repetitive negative thinking, cognitive reactivity, emotional allowance, mindfulness skills, and self-compassion will be tested as potential mediating factors for the clinical effects of MBSR. Childhood trauma, personality traits and baseline brain activity patterns will be tested as potential moderators of the clinical outcomes. DISCUSSION: This study aims to provide valuable insights into the effectiveness of MBSR in reducing stress-related symptoms in a susceptible student population and crucially, to investigate its effects on stress regulation, and to identify who may benefit most from the intervention. TRIAL REGISTRATION: Registered on September 15, 2022, at clinicaltrials.gov, NCT05541263 .

Effect of striatal dopamine on Pavlovian bias. A large [¹8F]-DOPA PET study.

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 greater WM capacity and highlight the importance of interactions between striatal dopamine and WM capacity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A transdiagnostic view on MDD and ADHD: shared cognitive characteristics?

BACKGROUND: Major Depressive disorder (MDD) and Attention Deficit Hyperactivity Disorder (ADHD) are prevalent mental disorders that often co-occur. There is overlap in symptomatology between MDD and ADHD that complicates diagnostics and treatment selection. Hence, to aid diagnostics of single and comorbid disorders, we aimed to examine the discriminative power of common symptom measures and cognitive dysfunction to differentiate between participants diagnosed with MDD, ADHD, ADHD and comorbid MDD and without a mental disorder. METHODS: Four diagnosed groups were compared: MDD (n = 103), ADHD (n = 78), comorbid MDD + ADHD (n = 29), healthy controls (HC; n = 123). We examined between-group differences and discriminative functions of clinically validated self-report symptom questionnaires, as well as task-based and self-report measures of cognitive dysfunction. RESULTS: Based on the between group comparisons, all patient groups were characterized by clinically relevant levels of ADHD-symptomatology, executive dysfunction, and diminished cognitive performances in the domain of attention; even the MDD-only group. In addition, based on self-reported symptoms of MDD, ADHD, and executive dysfunction, discriminant function analysis classified all HC correctly (100%) and patients diagnosed with ADHD or MDD relatively well (resp. 85% and 82%). Comorbid MDD + ADHD was poorly differentiated from single MDD or ADHD by the commonly used self-report symptom questionnaires for MDD and ADHD (0% correct predictions), which substantially improved by incorporating the questionnaire on executive functioning (42% correct predictions). CONCLUSIONS: In both MDD and ADHD, clinical levels of attentional and executive dysfunction were found, while these clinical groups differed in cognitive flexibility, initiating, inhibition and meta-cognition. Comorbid MDD + ADHD was poorly distinguishable from non-comorbid MDD and ADHD based on self-reported symptoms of depression and ADHD. Addition of subjective executive function in the discrimination models resulted in increased discriminative power. Our findings indicate that executive functioning measure can improve the diagnostic process of ADHD and MDD.

The effect of mindfulness-based cognitive therapy on rumination and a task-based measure of intrusive thoughts in patients with bipolar disorder.

BACKGROUND: Preliminary evidence suggests that Mindfulness-Based Cognitive Therapy (MBCT) is a promising treatment for bipolar disorder (BD). A proposed working mechanism of MBCT in attenuating depressive symptoms is reducing depressive rumination. The primary aim of this study was to investigate the effect of MBCT on self-reported trait depressive rumination and an experimental state measure of negative intrusive thoughts in BD patients. Exploratively, we investigated the effect of MBCT on positive rumination and positive intrusive thoughts. METHODS: The study population consisted of a subsample of bipolar type I or II patients participating in a multicenter randomized controlled trial comparing MBCT + treatment as usual (TAU) (N = 25) to TAU alone (N = 24). Trait depressive rumination (RRS brooding subscale) and intrusive thoughts (breathing focus task (BFT)) were assessed at baseline (full subsample) and post-treatment (MBCT + TAU; n = 15, TAU; n = 15). During the BFT, participants were asked to report negative, positive and neutral intrusive thoughts while focusing on their breathing. RESULTS: Compared to TAU alone, MBCT + TAU resulted in a significant pre- to post-treatment reduction of trait depressive rumination (R2 = .16, F(1, 27) = 5.15, p = 0.031; medium effect size (f2 = 0.19)) and negative intrusive thoughts on the BFT (R2 = .15, F(1, 28) = 4.88, p = 0.036; medium effect size (f2 = 0.17)). MBCT did not significantly change positive rumination or positive intrusive thoughts. CONCLUSIONS: MBCT might be a helpful additional intervention to reduce depressive rumination in BD which might reduce risk of depressive relapse or recurrence. Considering the preliminary nature of our findings, future research should replicate our findings and explore whether this reduction in rumination following MBCT indeed mediates a reduction in depressive symptoms and relapse or recurrence in BD.

Aversive Pavlovian inhibition in adult attention-deficit/hyperactivity disorder and its restoration by mindfulness-based cognitive therapy.

Background: Control over the tendency to make or withhold responses guided by contextual Pavlovian information plays a key role in understanding impulsivity and hyperactivity. Here we set out to assess (1) the understudied relation between contextual Pavlovian inhibitory control and hyperactivity/impulsivity in adults with ADHD and (2) whether this inhibition can be enhanced by mindfulness based cognitive therapy (MBCT). Methods: Within the framework of a randomized controlled trial 50 Adult ADHD patients were assessed before and after 8 weeks of treatment as usual (TAU) with (n = 24) or without (n = 26) MBCT. We employed a well-established behavioral Pavlovian-to-instrumental transfer task that quantifies Pavlovian inhibitory control over instrumental behavior. Results: Task results revealed (1) less aversive Pavlovian inhibition in ADHD patients with clinically relevant hyperactivity/impulsivity than in those without; and (2) enhanced Pavlovian inhibition across all ADHD patients after TAU+MBCT compared with TAU. Conclusion: These findings offer new insights in the neurocognitive mechanisms of hyperactivity/impulsivity in ADHD and its treatment: We reveal a role for Pavlovian inhibitory mechanisms in understanding hyperactive/impulsive behaviors in ADHD and point toward MBCT as an intervention that might influence these mechanisms.

Amygdala response predicts clinical symptom reduction in patients with borderline personality disorder: A pilot fMRI study.

Borderline personality disorder (BPD) is a prevalent, devastating, and heterogeneous psychiatric disorder. Treatment success is highly variable within this patient group. A cognitive neuroscientific approach to BPD might contribute to precision psychiatry by identifying neurocognitive factors that predict who will benefit from a specific treatment. Here, we build on observations that BPD is accompanied by the enhanced impact of the aversive effect on behavior and abnormal neural signaling in the amygdala. We assessed whether BPD is accompanied by abnormal aversive regulation of instrumental behavior and associated neural signaling, in a manner that is predictive of symptom reduction after therapy. We tested a clinical sample of 15 female patients with BPD, awaiting dialectical behavior therapy (DBT), and 16 matched healthy controls using fMRI and an aversive Pavlovian-to-instrumental transfer (PIT) task that assesses how instrumental behaviors are influenced by aversive Pavlovian stimuli. Patients were assessed 1 year after the start of DBT to quantify changes in BPD symptom severity. At baseline, behavioral aversive PIT and associated neural signaling did not differ between groups. However, the BOLD signal in the amygdala measured during aversive PIT was associated with symptom reduction at 1-year follow-up: higher PIT-related aversive amygdala signaling before treatment was associated with reduced clinical improvement at follow-up. Thus, within the evaluated group of BPD patients, the BOLD signal in the amygdala before treatment was related to clinical symptom reduction 1 year after the start of treatment. The results suggest that less PIT-related responsiveness of the amygdala increases the chances of treatment success. We note that the relatively small sample size is a limitation of this study and that replication is warranted.

Psychopathic tendency in violent offenders is associated with reduced aversive Pavlovian inhibition of behavior and associated striatal BOLD signal.

Background: Violent offenders with psychopathic tendencies are characterized by instrumental, i.e., planned, callous, and unemotional (aggressive) behavior and have been shown to exhibit abnormal aversive processing. However, the consequences of abnormal aversive processing for instrumental action and associated neural mechanisms are unclear. Materials and methods: Here we address this issue by using event-related functional magnetic resonance imaging (fMRI) in 15 violent offenders with high psychopathic tendencies and 18 matched controls during the performance of an aversive Pavlovian-to-instrumental transfer paradigm. This paradigm allowed us to assess the degree to which aversive Pavlovian cues affect instrumental action and associated neural signaling. Results: Psychopathic tendency scores were associated with an attenuation of aversive Pavlovian inhibition of instrumental action. Moreover, exploratory analyses revealed an anomalous positive association between aversive inhibition of action and aversive inhibition of BOLD signal in the caudate nucleus of violent offenders with psychopathic tendencies. In addition, psychopathic tendency also correlated positively with amygdala reactivity during aversive versus neutral cues in Pavlovian training. Conclusion: These findings strengthen the hypothesis that psychopathic tendencies in violent offenders are related to abnormal impact of aversive processing on instrumental behavior. The neural effects raise the possibility that this reflects deficient transfer of aversive Pavlovian inhibitory biases onto neural systems that implement instrumental action, including the caudate nucleus.

Neural correlates of repetitive negative thinking: Dimensional evidence across the psychopathological continuum.

Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders.

Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET): Protocol for a Cross-sectional Comorbidity Study From a Research Domain Criteria Perspective.

BACKGROUND: It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). OBJECTIVE: The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. METHODS: This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged ≥18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. RESULTS: We aim to include a total of 650 patients and 150 neurotypical control participants in the time period between 2016 and 2022. In October 2021, we are at 95% of our target. CONCLUSIONS: The MIND-SET study enables us to investigate the mechanistic underpinnings of nonpsychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

Mechanisms of Change in Mindfulness-Based Cognitive Therapy in Adults With ADHD.

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.

Putting mindfulness-based cognitive therapy to the test in routine clinical practice: A transdiagnostic panacea or a disorder specific intervention?

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.

Effects of methylphenidate on reinforcement learning depend on working memory capacity.

RATIONALE: Brain catecholamines have long been implicated in reinforcement learning, exemplified by catecholamine drug and genetic effects on probabilistic reversal learning. However, the mechanisms underlying such effects are unclear. OBJECTIVES AND METHODS: Here we investigated effects of an acute catecholamine challenge with methylphenidate (20 mg, oral) on a novel probabilistic reversal learning paradigm in a within-subject, double-blind randomised design. The paradigm was designed to disentangle effects on punishment avoidance from effects on reward perseveration. Given the known large individual variability in methylphenidate's effects, we stratified our effects by working memory capacity and trait impulsivity, putatively modulating the effects of methylphenidate, in a large sample (n = 102) of healthy volunteers. RESULTS: Contrary to our prediction, methylphenidate did not alter performance in the reversal phase of the task. Our key finding is that methylphenidate altered learning of choice-outcome contingencies in a manner that depended on individual variability in working memory span. Specifically, methylphenidate improved performance by adaptively reducing the effective learning rate in participants with higher working memory capacity. CONCLUSIONS: This finding emphasises the important role of working memory in reinforcement learning, as reported in influential recent computational modelling and behavioural work, and highlights the dependence of this interplay on catecholaminergic function.

The effectiveness of mindfulness-based cognitive therapy for major depressive disorder: evidence from routine outcome monitoring data.

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.

Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study.

Deficits in instrumental, goal-directed control, combined with the influence of drug-associated Pavlovian-conditioned stimuli, are thought to influence the development and maintenance of addiction. However, direct evidence has mainly come from animal studies. We sought to establish whether alcohol use disorder (AUD) is characterized by behavioral or neurobiological deficits in (i) the integration of Pavlovian and instrumental values and (ii) goal-directed control; and (iii) whether duration or severity of AUD is associated with such deficits. The influence of cues predicting food rewards on instrumental action was assessed in a Pavlovian-to-instrumental transfer (PIT) test, measuring both specific and general PIT, and goal-directed behavior in an outcome-devaluation test. Brain activity was measured using functional MRI in 38 abstinent individuals with AUD and 22 matched healthy control individuals (HCs). We found significant specific and general PIT and outcome-devaluation effects across groups indicating goal-directed control, mediated by distinct corticostriatal signals, but no significant differences between individuals with AUD and healthy controls. Bayesian analyses provided substantial-to-strong evidence for the absence of group differences for these effects, or any relationship with duration or severity of AUD. These results suggest intact ability to integrate action-outcome associations on specific and general PIT and goal-directed learning in AUD during abstinence.