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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (N ADHD =312, N NoADHD =305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g., Ruminococcus&#95;torques&#95;group (LogOdds=0.17, p fdr =4.42 × 10 -2 ), which was more abundant in adults with ADHD, and Eubacterium&#95;xylanophilum&#95;group (LogOdds= -0.12, p fdr =6.9 × 10 -3 ), which was less abundant in ADHD. Ruminococcus&#95;torques&#95;group was further associated with hyperactivity/impulsivity symptoms and Eisenbergiella with inattention and hyperactivity/impulsivity (p fdr <0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties., Competing Interests: Declaration of competing interest J.A.R.Q was on the speakers’ bureau and/or acted as consultant for Biogen, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Janssen- Cilag, Shire, Oryzon, Roche, Psious, and Rubió. BF has received educational speaking fees from Medice. IT receives funding from the Dutch organisation of research (ZONMW project numbers 80-86200-98-20006, 80-85200-98-20006, 60-63600-98-903) VR has served as a speaker for Rubió and Shire/Takeda in the last 5 years. She has received travel awards from Shire/Takeda for participating in psychiatric meetings. JKB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. BJ, PV, DM, PvE, MR, JV, MB, AAV and MH have nothing further to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Cognitive bias modification (CBM) has evolved from an experimental method testing cognitive mechanisms of psychopathology to a promising tool for accessible digital mental health care. While we are still discovering the conditions under which clinically relevant effects occur, the dire need for accessible, effective, and low-cost mental health tools underscores the need for implementation where such tools are available. Providing our expert opinion as Association for Cognitive Bias Modification members, we first discuss the readiness of different CBM approaches for clinical implementation, then discuss key considerations with regard to implementation. Evidence is robust for approach bias modification as an adjunctive intervention for alcohol use disorders and interpretation bias modification as a stand-alone intervention for anxiety disorders. Theoretical predictions regarding the mechanisms by which bias and symptom change occur await further testing. We propose that CBM interventions with demonstrated efficacy should be provided to the targeted populations. To facilitate this, we set a research agenda based on implementation frameworks, which includes feasibility and acceptability testing, co-creation with end-users, and collaboration with industry partners., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity., Methods: The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status., Results: Four functional domains, aligning with RDoC's negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas, CHKCI001, Clostridium sensu stricto 1, Oscillibacter, and Flavonifractor; social processes with Sellimonas; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all p FDR  < 0.05)., Conclusion: Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Our memory is crucial to our daily functioning, our identity, and how we interact with the world around us. Maintaining memory functioning is therefore important in many ways. Exercise positively affects our memory. Even a single exercise session can directly boost different memory types, including working, procedural, and episodic memory. Due to these benefits, exercise has great potential as an intervention in different settings, such as schools or rehabilitation centers, and as a prevention strategy. In this chapter, we first give an overview of what memory is and why it is so relevant to our mental health. Next, we briefly discuss how, for whom, and under which circumstances exercise improves memory functioning. Then, we will summarize the literature of experimental studies investigating the direct effect of exercise on different memory types, while acknowledging current limitations and potential future directions. Finally, we briefly highlight the potential of exercise as intervention to preserve and improve memory., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Functional neuroimaging has contributed substantially to understanding brain function but is dominated by group analyses that index only a fraction of the variation in these data. It is increasingly clear that parsing the underlying heterogeneity is crucial to understand individual differences and the impact of different task manipulations. We estimate large-scale (N = 7728) normative models of task-evoked activation during the Emotional Face Matching Task, which enables us to bind heterogeneous datasets to a common reference and dissect heterogeneity underlying group-level analyses. We apply this model to a heterogenous patient cohort, to map individual differences between patients with one or more mental health diagnoses relative to the reference cohort and determine multivariate associations with transdiagnostic symptom domains. For the face>shapes contrast, patients have a higher frequency of extreme deviations which are spatially heterogeneous. In contrast, normative models for faces>baseline have greater predictive value for individuals' transdiagnostic functioning. Taken together, we demonstrate that normative modelling of fMRI task-activation can be used to illustrate the influence of different task choices and map replicable individual differences, and we encourage its application to other neuroimaging tasks in future studies., (© 2024. The Author(s).)

Background: Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples., Methods: In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns., Results: We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment., Limitations: Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations., Conclusions: Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Competing interest The authors declare to have no potential conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Mindfulness-based cognitive therapy (MBCT) is an evidence-based treatment for depression. The current study focused on the long-term outcomes of MBCT for chronically, treatment-resistant depressed patients during a 6-months follow-up period. Additionally, predictors of treatment outcomes were explored., Method: The outcomes of MBCT on depressive symptoms, remission rates, quality of life, rumination, mindfulness skills and self-compassion were investigated in a cohort of chronically, treatment-resistant depressed outpatients (N = 106), who had taken part in an RCT comparing MBCT with treatment-as-usual (TAU). Measures were assessed pre-MBCT, post-MBCT, at 3-months follow-up, and at 6-months follow-up., Results: Results of linear mixed effect models and Bayesian repeated measures ANOVA's reveal that depressive symptoms, quality of life, rumination, mindfulness skills and self-compassion consolidated during follow-up. Remission rates even further increased over the course of follow-up. When controlling for symptoms at baseline, higher baseline levels of rumination predicted lower depressive symptoms and quality of life at 6-month follow-up. No other predictors (i.e. duration of current depressive episode, level of treatment-resistance, childhood trauma, mindfulness skills, self-compassion) were found., Limitations: All participants received MBCT, therefore time or other non-specific effects might have influenced the results and replication studies including a control conditions are needed., Conclusions: Results indicate that the clinical benefits of MBCT for chronically, treatment-resistant depressed patients persist up to 6 months after completing MBCT. Duration of the current episode, level of treatment-resistance, childhood trauma and baseline levels of mindfulness skills and self-compassion did not predict treatment outcome. When controlling for baseline depressive symptoms participants with high levels of rumination seem to benefit more; however more research is needed., Trial Registry: Dutch Trial Registry, number NTR4843., Competing Interests: Declaration of competing interest A.E.M. Speckens is founder and clinical director of the Radboudumc Centre for Mindfulness. She is mindfulness trainer and occasionally receives payments for training workshops and presentations related to mindfulness-based cognitive therapy. A.E.M. Speckens donates all such fees to Radboud university medical center. M.B. Cladder-Micus, J. N. Vrijsen, A. Fest, A.R.T. Donders, J. Spijker, and E.S. Becker declare they have no potential conflicts of interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The benefits of peer support interventions (PSIs) for individuals with mental illness are not well known. The aim of this systematic review and meta-analysis was to assess the effectiveness of PSIs for individuals with mental illness for clinical, personal, and functional recovery outcomes., Methods: Searches were conducted in PubMed, Embase, and PsycINFO (December 18, 2020). Included were randomized controlled trials (RCTs) comparing peer-delivered PSIs to control conditions. The quality of records was assessed using the Cochrane Collaboration Risk of Bias tool. Data were pooled for each outcome, using random-effects models., Results: After screening 3455 records, 30 RCTs were included in the systematic review and 28 were meta-analyzed (4152 individuals). Compared to control conditions, peer support was associated with small but significant post-test effect sizes for clinical recovery , g = 0.19, 95% CI (0.11-0.27), I 2 = 10%, 95% CI (0-44), and personal recovery, g = 0.15, 95% CI (0.04-0.27), I 2 = 43%, 95% CI (1-67), but not for functional recovery , g = 0.08, 95% CI (-0.02 to 0.18), I 2 = 36%, 95% CI (0-61). Our findings should be considered with caution due to the modest quality of the included studies., Conclusions: PSIs may be effective for the clinical and personal recovery of mental illness. Effects are modest, though consistent, suggesting potential efficacy for PSI across a wide range of mental disorders and intervention types.

Background: Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders., Methods: We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients ( N = 557)., Results: Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity., Conclusions: The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

In line with the Research Domain Criteria (RDoC) , we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health-related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus, and thalamus across the different modalities of this component may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems, and sensitivity to sensory stimuli, respectively. Taken together, the findings from our extensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology., Competing Interests: Jv, AL, NK, TM, RC, FD, JV, CB, AS, GF, IT, Pv No competing interests declared, (© 2023, van Oort et al.)

Although it is well known that exercise reduces depressive symptoms, the underlying psychological mechanisms remain unclear. This experimental study examined the acute effect of exercise on mood, and depressotypic memory bias and state rumination. Trait rumination was tested as a possible moderator. A sample of non-regular exercisers ( N  = 100) was randomized to exercise or rest. After a negative mood induction, the exercise condition cycled for 24 min at moderate intensity, while the rest condition rested. Negative and overgeneral memory bias, as well as positive and negative affect were assessed after exercise/rest. To capture the lingering of negative mood and state rumination, both were assessed multiple times throughout the study. The exercise (as compared to rest) condition reported more positive affect. However, no differences were found on overgeneral memory bias, as well as depression-specific mood or state rumination measured throughout the study. Interestingly, the exercise condition showed more negative memory bias at higher levels of rumination. Individual differences in trait rumination moderated the exercise-memory bias relation, such that exercise increased negative memory bias at higher levels of rumination. It is possible that long-term exercise protocols are necessary to change cognitive processes related to depression.

Background: Heterogeneity and comorbidity in psychiatric disorders are common, however, little is known about the impact on well-being and the role of functional limitations. We aimed to identify transdiagnostic psychiatric symptom profiles and to study their association with well-being and the mediating role of functional limitations in a naturalistic psychiatric patient group., Methods: We used four disorder-specific questionnaires to assess symptom severity within a sample of 448 psychiatric patients with stress-related and/or neurodevelopmental disorders and 101 healthy controls. Using both exploratory and confirmatory factor analyses we identified transdiagnostic symptom profiles, which we entered into a linear regression analysis to assess their association with well-being and the mediating role of functional limitations in this association., Results: We identified eight transdiagnostic symptom profiles, covering mood, self-image, anxiety, agitation, empathy, non-social interest, hyperactivity and cognitive focus. Mood and self-image showed the strongest association with well-being in both patients and controls, while self-image also showed the highest transdiagnostic value. Functional limitations were significantly associated with well-being and fully mediated the relationship between cognitive focus and well-being., Limitations: The participant sample consisted of a naturalistic group of out-patients. While this strengthens the ecological validity and transdiagnostic perspective of this study, the patients with a single neurodevelopmental disorder were underrepresented., Conclusion: Transdiagnostic symptom profiles are valuable in understanding what reduces well-being in psychiatric populations, thereby opening new avenues for functionally meaningful interventions., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cognitive theories of depression hold that negative contextual triggers (e.g., stressful events) induce more negative and less positive mood, in turn instigating negatively biased memories. However, context-related variability in mood and emotional memory has received insufficient attention, while the dynamic interaction between these factors plays a crucial role in the kindling of new depressive episodes. Experience Sampling Method (ESM) for repeated, daily life measures of context, mood, and autobiographic emotional memory was used in 46 currently depressed, 90 remitted-depressed, and 55 never-depressed individuals. Currently depressed individuals showed strongest negative processing style and never-depressed most positive, with remitted-depressed patients scoring intermediate. The moderated mediation model indicated that context appraisal had a direct effect on the appraisal of the recalled event (i.e., our operationalization of emotional memory), which was mediated by positive (but hardly by negative) mood and was independent of depression status. This mediation strength was relatively similar to the strength of the direct effect of context on memory. Results are in line with cognitive theories of depression. Especially context seems important for emotional memory. The association between context, mood, and memory, however, may be independent of depression status. Yet, the "level" of mood, context, and event appraisal does depend on depression status. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum-a central hub in motor, cognitive, affective and reward-related brain circuits-and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry., (© 2022. The Author(s).)

Negative memory bias refers to the enhanced recall of negative memories and is a prominent cognitive factor causing and maintaining depression. Surprisingly few studies modify this negative recall. The current study used a smartphone-based autobiographical memory training to increase positive memory recall and thereby alter negative memory bias. A total of 96 dysphoric (≥ 13 BDI-II) participants were randomly allocated to a positive, sham or no-training condition, conducted over a period of 6 days. Positive memory bias (i.e., recalled event evaluation) significantly increased from pre- to post-training after positive and sham intervention, suggesting an unspecific training effect. No transfer to memory specificity, implicit memory bias or depressive symptoms was found, nor was the training effect modulated by pre-existing level of positive memory bias. A post-hoc follow-up measurement during the initial COVID-19 crisis revealed that subjects who benefitted most from either of the trainings maintained their stress levels better during a natural stressful period, compared to those who responded least to the training. Future studies should carefully consider the impact of sham training design. Moreover, it is important to examine transfer effects of bias training as practice in daily life., (© 2022. The Author(s).)

Background: The chronic nature of depression and limited availability of evidence-based treatments emphasize the need for complementary recovery-oriented services, such as peer support interventions (PSIs). Peer support is associated with positive effects on clinical and personal recovery from mental illness, but little is known about the processes of engagement that foster change, and studies targeting individuals with depression specifically are limited., Objective: This study aimed to evaluate whether the level of user engagement, assessed on several dimensions, in an online peer support community for individuals with depression promotes empowerment and the use of self-management strategies and reduces symptom severity and disability., Methods: In a longitudinal survey conducted from June 2019 to September 2020, we analyzed the data of the users of Depression Connect (DC), an online peer support community hosted by the Dutch Patient Association for Depression and the Pro Persona Mental Health Care institute, on measures of empowerment, self-management, depression, and disability. Of the 301 respondents, 49 (16.3%) respondents completed the survey again after 3 months and 74 (24.6%) respondents, after 6 months. Analysis of 3 parameters (ie, total time spent on the platform, number of page views, and number of posts) derived from their data logs yielded 4 engagement profiles. Linear mixed models were fitted to determine whether the outcomes had significantly changed over time and differed for the various profiles., Results: Baseline engagement with the online peer support community was "very low" (177/301, 58.8%) or "low" (87/301, 28.9%) for most of the participants, with few showing "medium" (30/301, 9.9%) or "high" engagement patterns (7/301, 2.3%), while user profiles did not differ in demographic and clinical characteristics. Empowerment, self-management, depressive symptoms, and disability improved over time, but none were associated with the intensity or nature of user engagement., Conclusions: With most DC members showing very low to low engagement and only a few being identified as high-engaged users, it is likely that this flexibility in use frequency is what provides value to online PSI users. In other more formal supportive environments for depression, a certain level of engagement is predetermined either by their organizational or by their societal context; at DC, users can adapt the intensity and nature of their engagement to their current needs on their personal road to recovery. This study added to the current knowledge base on user engagement for PSIs because previous studies targeting depression with an online format focused on active users, precluding passive and flexible engagement. Future studies should explore the content and quality of the interactions in online PSIs to identify optimal user engagement as a function of current, self-reported clinical parameters and reasons to engage in the PSI., (©Dorien Smit, Janna N Vrijsen, Theo Broekman, Bart Groeneweg, Jan Spijker. Originally published in JMIR Formative Research (https://formative.jmir.org), 02.11.2022.)

Objectives: Depression and ADHD often co-occur and are both characterized by altered attentional processing. Differences and overlap in the profile of attention to emotional information may help explain the co-occurence. We examined negative attention bias in ADHD as neurocognitive marker for comorbid depression., Methods: Patients with depression ( n  = 63), ADHD ( n  = 43), ADHD and depression ( n  = 25), and non-psychiatric controls ( n  = 68) were compared on attention allocation toward emotional faces. The following eye-tracking indices were used: gaze duration, number of revisits, and location and duration of first fixation., Results: Controls revisited the happy faces more than the other facial expressions. Both the depression and the comorbid group showed significantly less revisits of the happy faces compared to the ADHD and the control group. Interestingly, after controlling for depressive symptoms, the groups no longer differed on the number of revisits., Conclusion: ADHD patients show a relative positive attention bias, while negative attention bias in ADHD likely indicates (sub)clinical comorbid depression.

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., (Copyright © 2022 van Oort, Tendolkar, Collard, Geurts, Vrijsen, Duyser, Kohn, Fernández, Schene and van Eijndhoven.)

Self-referent negative memory bias is a known risk factor for depression, but recent evidence suggests its function as a transdiagnostic cognitive depressotypic marker. The amygdala's sensitivity for negative information is considered a neurobiological depressotypic marker. However, their relationship remains unknown. We transdiagnostically investigated the association between the amygdala's sensitivity, self-referent negative memory bias and its two components: negative endorsement bias and negative recall bias. Patients (n= 125) with (multimorbid) stress-related and neurodevelopmental psychiatric disorders and healthy controls (n= 78) performed an fMRI task to assess the amygdala's sensitivity for negative information and a task outside the scanner for the biases. Linear regression models assessed their associations. The left amygdala's sensitivity for negative information was significantly positively associated with negative recall bias in patients, but not controls. There were no significant associations with self-referent negative memory bias or negative endorsement bias or between the two depressotypic markers. Thus, the left amygdala's sensitivity for negative information may be considered a neural marker of negative memory bias across psychiatric diagnoses. Further research on the interactons with known determinants such as genetic predisposition is required to fully understand the relationship between the amygdala's sensitivity for negative information and these biases., (Copyright © 2022. Published by Elsevier B.V.)

Background: Classic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample., Methods: We administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling., Results: In contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias., Conclusions: These results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.

In this cross-sectional study we examined whether the prevalence of treatment resistant depression (TRD) can be partly attributed to level of bipolarity. We included data of 201 patients with either episodic depression or TRD, who received treatment for their depression at either an outpatient or 2nd opinion/daytime setting, within a specialised mental healthcare department in the Netherlands. Whether level of TRD, assessed by the 'Dutch Measure for quantification of Treatment Resistance in Depression', can be partly explained by level of bipolarity, assessed by 'the Bipolarity Index', was examined using linear regression. We found no direct association between level of TRD and level of bipolarity, nor did comorbid anxiety disorders obscure an existing association. In this study we found no evidence for overlooked bipolarity contributing to the high prevalence of TRD. If replicated, we could state that additional screening on bipolarity with an instrument such as the 'Bipolarity Index' in the specialised mental health care is unnecessary., (Copyright © 2021. Published by Elsevier B.V.)

Background: Already a major health concern, late-life depression (LLD) is expected to form an increasing problem in the aging population. Moreover, despite current treatments, LLD is associated with a poor long-term prognosis and high rate of chronicity. Treatment provision and treatment accordingly warrant improvement, where add-on treatments might contribute to the efficacy of conventional therapies. Although it is known that impaired cognitive control contributes to LDD, it is not targeted sufficiently by current interventions. Research on cognitive control training (CCT) shows promising results on depressive symptoms, cognitive performance, and overall functioning. However, further research is needed to determine the long-term effects of CCT on LLD, its cost-effectiveness, and mechanisms of change., Methods: In the current multicenter randomized controlled trial (RCT) with a between-subjects design participants aged 60 years and over with a current LLD receiving treatment as usual (TAU) are randomized to add-on CCT or placebo training. Randomization is stratified by depression severity. Participants will receive eight online CCT or placebo sessions spread across four consecutive weeks. They will complete a post-training assessment after 1 month and three follow-up assessments scheduled three, six and 12 months after completing the training. We expect CCT and TAU to be more (cost-)effective in reducing depressive symptoms than placebo training and TAU. Additionally, we will be looking at secondary clinical, cognitive and global functioning outcomes and likely mechanisms of change (e.g., improved cognitive functioning, reduced rumination, and improved inhibition of negative stimuli)., Discussion: The proposed RCT aims to contribute to the clinical and scientific knowledge on the long-term effects of CCT as an add-on treatment for LLD. Cost-effectiveness is particularly relevant considering the expected volume of the target demographic. The study will be a pragmatic trial with few inclusion restrictions, providing information on feasibility of web-based trainings in clinical settings. The outcomes are potentially generalizable to guidelines for treatment of LLD., Trial Registration: This trial is registered in the Netherlands Trial Register (code: NL7639 ). Registered 3 april 2019., (© 2021. The Author(s).)

Heightened attention towards negative information is characteristic of depression. Evidence is emerging for a negative attentional bias in Autism spectrum disorder (ASD), perhaps driven by the high comorbidity between ASD and depression. We investigated whether ASD is characterised by a negative attentional bias and whether this can be explained by comorbid (sub) clinical depression. Participants (n = 116) with current (CD) or remitted depression (RD) and/or ASD, and 64 controls viewed positively and negatively valenced (non-)social pictures. Groups were compared on three components of visual attention using linear mixed models. Both CD individuals with and without ASD, but not remitted depressed and never-depressed ASD individuals showed a negative bias, suggesting that negative attentional bias might be a depressive state-specific marker for depression in ASD., (© 2021. The Author(s).)

Objective: Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients., Methods: Data from 260 naturalistic psychiatric outpatients were used. Psychiatric diagnoses were based on structured clinical interviews. Somatic diseases were assessed using a well-validated questionnaire and were clustered into (cardio)vascular and immune/endocrine diseases. PC was operationalized using the Perseverative Thinking Questionnaire (PTQ)., Results: Multiple regression complemented with relative importance analyses showed that the PTQ total and subscale scores were associated with the presence of mood disorders, addiction, and anxiety. Unexpectedly, no relatively important associations were found between the PTQ and autism spectrum disorder, attention-deficit/hyperactivity disorder, or somatic disease., Conclusions: Our data complement previous work linking PC to stress-related mental disorders but question its immediate role in neurodevelopmental and somatic disorders. Targeting PC in the treatment of mood disorders and perhaps also in addiction seems promising., (Copyright © 2021 by the American Psychosomatic Society.)

Attentional deficits as well as attentional biases towards negative material are related to major depression and might maintain chronicity. However, studies investigating attentional deficits and attentional biases in chronic, treatment-resistant depressed are lacking. The aim of the current study was to compare measures of attentional deficits and attentional bias between chronic, treatment-resistant depressed outpatients and never-depressed control participants. Attentional deficits were assessed with the attentional control scale (ACS) and the Stroop Color naming task. Attentional bias was measured with the exogenous cueing task (ECT) and an emotional Stroop task. Chronic, treatment-resistant depressed patients (n = 80) showed significantly more attentional deficits than never-depressed controls (n = 113) on the ACS and Stroop color-naming task. However, in contrast with hypotheses, no differences were found between chronic, treatment-resistant depressed patients and never-depressed individuals on the ECT or emotional Stroop task. The current findings indicate that chronic, treatment-resistant depressed patients present attentional deficits. The results however question whether this patient group shows attentional biases for negative material. Future research should include comparisons of chronic, treatment-resistant and non-chronically depressed patients. If replicated, these current results might indicate that focusing on improving attentional deficits could be a more promising target for treatment than addressing attentional biases., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Internet support groups enable users to provide peer support by exchanging knowledge about and experiences in coping with their illness. Several studies exploring the benefits of internet support groups for depression have found positive effects on recovery-oriented values, including empowerment. However, to date, little attention has been paid to user narratives., Objective: This study aims to capture the user perspective on an online peer support community for depression with a focus on the modes of user engagement and the benefits users derive from participation in the forum., Methods: In this qualitative study, we conducted 15 semistructured interviews with users of Depression Connect, a newly developed online peer support community for individuals with depression. Combining a concept-driven and a data-driven approach, we aimed to gain insight into what users value in our Depression Connect platform and whether and how the platform promotes empowerment. We performed a thematic analysis to explore the merits and demerits reported by users by using theoretical concepts widely used in internet support group research. In the subsequent data-driven analysis, we sought to understand the relationship between different styles of user engagement and the participants' experiences with the use of Depression Connect. Data analysis consisted of open, axial, and selective coding. To include as diverse perspectives as possible, we opted for purposive sampling. To verify and validate the (interim) results, we included negative cases and performed member checks., Results: We found participation in Depression Connect contributes to a sense of belonging, emotional growth, self-efficacy, and empowerment. "Getting too caught up" was the most frequently reported negative aspect of using Depression Connect. The deployment and development of three participation styles (ie, reading, posting, and responding) affected the perceived benefits of Depression Connect use differentially, where the latter style was central to enhancing empowerment. "Being of value to others" boosted the users' belief in their personal strength. Finally, Depression Connect was predominantly used to supplement offline support and care for depression, and it mainly served as a safe environment where members could freely reflect on their coping mechanisms for depression and exchange and practice coping strategies., Conclusions: Our findings shed new light on user engagement processes on which internet support groups rely. The online community primarily served as a virtual meeting place to practice (social) skills for deployment in the offline world. It also allowed the members to learn from each other's knowledge and experiences and explore newly gained insights and coping skills., (©Dorien Smit, Janna N Vrijsen, Bart Groeneweg, Amber Vellinga-Dings, Janneke Peelen, Jan Spijker. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 12.07.2021.)

Background: Prior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: patients with depression seem to learn more from punishment than from reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in patients with MDD and comorbid disorders and whether this bias is specific to depression or shared across disorders., Methods: We employed a transdiagnostic approach assessing a heterogeneous group of (nonpsychotic) psychiatric patients from the MIND-Set (Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders) cohort with and without MDD but also with anxiety, attention-deficit/hyperactivity disorder, and/or autism (n = 66) and healthy control subjects (n = 24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional magnetic resonance imaging., Results: In contrast to previous studies, patients with MDD did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in the bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, attention-deficit/hyperactivity disorder, and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly that associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward., Conclusions: Prefrontal enhancement may reflect compensatory working memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Alexithymia-reflecting deficits in cognitive emotion processing-is highly prevalent in individuals with depressive disorders. Subsequently, mixed evidence for attentional bias is found in these individuals. Alexithymia may be a potential influencing factor for attentional bias in depression. In the current study, 83 currently depressed (CD) and 76 never-depressed (ND) controls completed an eye-tracker task consisting of valenced (non)-social pictures. Alexithymia scores were also included as a moderator as both a continuous and categorical measure (so high vs. low alexithymia). No group difference or moderating effect of alexithymia was found on attentional bias. Thus, alexithymic symptoms, included both dimensionally and categorically, may not influence biased attentional processing in depression compared to ND individuals. Thus, it is important to explore other potential explaining factors for the equivocal results found on biased attentional processing of emotional information in depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bergman, Vissers, Collard, van Eijndhoven, Schene and Vrijsen.)

Background: Major depressive disorder (MDD) is a considerable public health concern. In spite of evidence-based treatments for MDD, many patients do not improve and relapse is common. Therefore, improving treatment outcomes is much needed and adjunct exercise treatment may have great potential. Exercise was shown to be effective as monotherapy for depression and as augmentation strategy, with evidence for increasing neuroplasticity. Data on the cost-effectiveness and the long-term effects of adjunct exercise treatment are missing. Similarly, the cognitive pathways toward remission are not well understood., Methods: The present study is designed as a multicenter randomized superiority trial in two parallel groups with follow-up assessments up to 15 months. Currently depressed outpatients (N = 120) are randomized to guideline concordant Standard Care (gcSC) alone or gcSC with adjunct exercise treatment for 12 weeks. Randomization is stratified by gender and setting, using a four, six, and eight block design. Exercise treatment is offered in accordance with the NICE guidelines and empirical evidence, consisting of one supervised and two at-home exercise sessions per week at moderate intensity. We expect that gcSC with adjunct exercise treatment is more (cost-)effective in decreasing depressive symptoms compared to gcSC alone. Moreover, we will investigate the effect of adjunct exercise treatment on other health-related outcomes (i.e. functioning, fitness, physical activity, health-related quality of life, and motivation and energy). In addition, the mechanisms of change will be studied by exploring any change in rumination, self-esteem, and memory bias as possible mediators between exercise treatment and depression outcomes., Discussion: The present trial aims to inform the scientific and clinical community about the (cost-)effectiveness and psychosocial mechanisms of change of adjunct exercise treatment when implemented in the mental health service setting. Results of the present study may improve treatment outcomes in MDD and facilitate implementation of prescriptive exercise treatment in outpatient settings., Trial Registration: This trial is registered within the Netherlands Trial Register (code: NL8432 , date: 6th March, 2020).

Background: Negative memory bias is a strong risk factor for the development and maintenance of depression. Recent evidence also found negative memory bias in other mental disorders. Here, we aim to: 1) assess the presence and strength of negative memory bias in a range of (comorbid) mental disorders, 2) investigate which disorder-specific symptoms are associated with negative memory bias, and 3) test whether negative memory bias might be a transdiagnostic mechanism., Methods: Negative memory bias was measured in patients with at least one diagnosis of a stress-related disorder (n = 86), a neurodevelopmental disorder (n = 53), or both (n = 68), and 51 controls. Depression, anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorder symptom severity was assessed using questionnaires. Groups were compared on negative memory bias and the associations between negative memory bias and symptom severity were made using linear regression models., Results: All patient groups showed stronger negative memory bias than the controls. Negative memory bias was individually associated with all symptom severity indices, but when added into a single model, only the association with depressive symptom severity remained. This persisted after controlling for diagnostic group., Limitations: Due to the cross-sectional sectional study design, we could only look at the associations between negative memory bias and disorder-specific symptoms and not at the direction of the effects., Conclusions: Negative memory bias is characteristic of a depressotypic processing style and present in different mental disorders. It might play a mechanistic role in the development of (subclinical) co-occurrence between mental disorders., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Background: Living with recurrent, and/or chronic depression requires long-term management in addition to active coping on a day-to-day basis. Previous research on long-term management, and coping with depression mainly focused on identifying self-management strategies. However, research on the conditions for deploying self-management strategies in depression is lacking. By means of exploring the development of experiential knowledge in depression, and its relation with coping with depression, this study aims to gain insight into the conditions for deploying self-management strategies., Methods: In the current qualitative study, individual pathways to recovery, living with depression, and recurrence risk were assessed, including but not limited to long-term management. 'Experiential knowledge', which can be defined as patients' unique knowledge and own lived experiences in facilitating and debilitating factors in the recovery process and coping with the disorder, was used as a sensitizing concept. Thirteen semi-structured interviews were conducted with individuals who experienced at least two depressive episodes and were currently in (partial) remission, plus two deviant cases were interviewed to check for saturation. Until saturation was achieved, participants were purposively selected to include diverse perspectives on coping with depression. Data were analysed using a narrative research method., Results: The results show that deploying self-management strategies are an integral part of 'experiential knowledge'. The evolvement of experiential knowledge can be seen as a cyclical process of the main themes that were identified as relevant when coping with depression: introspection, empowerment, self-management strategies, and external moderators of the environment. The identification of supporting and impeding factors in coping with depression from a patient perspective might increase a sustainable use of self-management strategies., Conclusion: These results highlight the need for an individualised holistic model of coping with depression, both in research, and in practice. By means of integrating experiential knowledge in this holistic approach, the conditions for deployment of self-management strategies in depressive patients can be specified.

We systematically review the literature on approach-avoidance (AA) tendencies in mental disorders, including 97 empirical studies. Most evidence for the role of biased AA tendencies was found in addictive disorders: The presence of an approach bias (ApB) for substance related stimuli in subclinical populations can be a risk factor for increased future substance use, and AA modification training given as an add-on to standard treatment has the potential to reduce intake and relapse rates reliably. In depression, reduced approach of positive stimuli and reduced avoidance of negative stimuli have been found, and modification procedures seem to have clinical potential. In anxiety disorders, an avoidance bias (AvB) for threat-related stimuli has been found frequently, but modification studies did not yield any clinical effects. In eating disorder a lack of food preferences in anorexia nervosa may be present, but relations between AA measures and clinical (outcome) measures were not established. In other disorders, the evidence was limited due to a low number of published studies. Several methodological problems are discussed: It is often difficult to compare studies to each other, control groups and control stimuli are frequently missing, and many studies suffer from insufficient statistical power due to small samples. We finally give suggestions for future research on biased AA tendencies in psychopathology., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Most mental health hospitals in the Netherlands use disorder specific standards of care. In case of comorbidity, we lack evidence in choosing the treatment of preference when both depressive- and anxiety disorder(s) are present in the same patient.
AIM: To investigate the prevalence of depression and anxiety (including obsessive compulsive disorder and post-traumatic stress disorder) in an outpatient mental health hospital population treated for their anxiety disorder, and to investigate the difference in outcome of (anxiety) treatment between patients with and without a comorbid depressive disorder.
METHOD: A retrospective study using outcome data from 2012 to 2017. In this period, we identified 127 patients for whom outcome data and diagnostic criteria were available. Comorbidity in this group was determined by a clinical interview. During treatment symptoms were monitored using self-reporting scales, among others the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI).
RESULTS: In 46,5% of the patients a comorbid depressive disorder was diagnosed. No significant difference in treatment outcome was observed between the group of patients with and the group of patients without a comorbid depressive disorder. However, the amount of reduction of depressive symptoms measured by the ids was a good predictor of the reduction of anxiety: a faster reduction of depressive symptoms predicts a better outcome of the treatment of anxiety.
CONCLUSION: Comorbid depressive disorders were observed in almost half of the patients treated in specialized (outpatient) clinics for anxiety disorders. A slower reduction of depressive symptoms predicts worse outcome of the treatment of anxiety.

Clinically, it is well-established that vulnerability to stress is a common feature across a broad spectrum of psychiatric disorders. However, this link has been mechanistically studied almost exclusively in patients with so-called stress-related disorders such as depression and anxiety. To probe transdiagnostic mechanisms, we set out to study the acute stress response across a broader range of psychiatric disorders taking a large-scale brain network perspective. We investigated the brain's response to a mild, experimentally well-controlled psychological stressor in the form of an aversive movie. We studied 168 patients with stress-related and/or neurodevelopmental disorders (including comorbidity) and 46 control subjects. We focused on three networks that have a central role in the brain's stress response and are affected in a wide range of psychiatric disorders: the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). Our results support an increased vulnerability to stress across all patients, indicated by a higher subjective stress level at baseline and follow-up compared to matched controls. At the brain systems level, the stress response was characterized by a relatively decreased FPN connectivity and an absence of a decrease in the within DMN connectivity across all disorders compared to controls. At the neurocognitive level, these findings may reflect a diminished top-down control and a tendency to more pronounced (negative) self-referential processing. Besides these shared aspects of the maladaptive stress response, we also discuss indications for disorder-specific aspects. Taken together, our results emphasize the importance of investigating the mechanistic underpinnings of psychiatric disorders transdiagnostically as recently done in neurogenetics., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

An interesting factor explaining recurrence risk in Major Depressive Disorder (MDD) may be neuropsychological functioning, i.e., processing of emotional stimuli/information. Negatively biased processing of emotional stimuli/information has been found in both acute and (inconclusively) remitted states of MDD, and may be causally related to recurrence of depression. We aimed to investigate self-referent, memory and interpretation biases in recurrently depressed patients in remission and relate these biases to recurrence. We included 69 remitted recurrent MDD-patients (rrMDD-patients), 35-65 years, with ≥2 episodes, voluntarily free of antidepressant maintenance therapy for at least 4 weeks. We tested self-referent biases with an emotional categorization task, bias in emotional memory by free recall of the emotion categorization task 15 min after completing it, and interpretation bias with a facial expression recognition task. We compared these participants with 43 never-depressed controls matched for age, sex and intelligence. We followed the rrMDD-patients for 2.5 years and assessed recurrent depressive episodes by structured interview. The rrMDD-patients showed biases toward emotionally negative stimuli, faster responses to negative self-relevant characteristics in the emotional categorization, better recognition of sad faces, worse recognition of neutral faces with more misclassifications as angry or disgusting faces and less misclassifications as neutral faces (0.001 < p < 0.05). Of these, the number of misclassifications as angry and the overall performance in the emotional memory task were significantly associated with the time to recurrence ( p ≤ 0.04), independent of residual symptoms and number of previous episodes. In a support vector machine data-driven model, prediction of recurrence-status could best be achieved (relative to observed recurrence-rate) with demographic and childhood adversity parameters (accuracy 78.1%; 1-sided p = 0.002); neuropsychological tests could not improve this prediction. Our data suggests a persisting (mood-incongruent) emotional bias when patients with recurrent depression are in remission. Moreover, these persisting biases might be mechanistically important for recurrence and prevention thereof.

Memory bias is a risk factor for depression. In two independent studies, the efficacy of one CBM-Memory session on negative memory bias and depressive symptoms was tested in vulnerable samples. We compared positive to neutral (control) CBM-Memory trainings in highly-ruminating individuals (N = 101) and individuals with elevated depressive symptoms (N = 100). In both studies, participants studied positive, neutral, and negative Swahili words paired with their translations. In five study-test blocks, they were then prompted to retrieve either only the positive or neutral translations. Immediately following the training and one week later, we tested cued recall of all translations and autobiographical memory bias; and also measured mood, depressive symptoms, and rumination. Retrieval practice resulted in training-congruent recall both immediately after and one week after the training. Overall, there was no differential decrease in symptoms or difference in autobiographical memory bias between the training conditions. In the dysphoric but not in the high-ruminating sample, the positive training resulted in positive autobiographical bias only in dysphoric individuals with positive pre-existing bias. We conclude that one session of positive retrieval-based CBM-Memory may not be enough to yield symptom change and affect autobiographical memory bias in vulnerable individuals.

Background: Only 60% of depressed patients respond sufficiently to treatment, so there is a dire need for novel approaches to improve treatment effects. Cognitive Bias Modification (CBM) may be an effective and easily implemented computerized add-on to treatment-as-usual. Therefore, we investigated the effects of a positivity-attention training and a positivity-approach training compared to control trainings., Methods: In a blinded randomized-controlled design, 139 depressed inpatients received either the CBM Attention Dot-Probe Training (DPT) or the CBM Approach-Avoidance Training (AAT), next to treatment as usual. N = 121 finished all four training sessions. Both trainings had an active and a control condition. In both active conditions, patients were trained to preferentially process generally positive pictures over neutral pictures. Depressive symptom severity was assessed before and after CBM, and positivity bias was measured at the start and end of each session., Results: Clinician-rated depressive symptom severity decreased more in patients who received the active condition of the DPT or the AAT compared to patients in the control conditions. Significant change in positivity bias was found for the DPT (not the AAT), but did not mediate the effect of the training on depressive symptoms., Conclusions: The results suggest that both types of CBM (i.e., DPT and AAT) may provide a fitting add-on treatment option for clinical depression. The working mechanisms and optimal dose of CBM trainings, plus their possible combination, should be examined in more detail., (Copyright © 2018. Published by Elsevier B.V.)

Background: Chronic and treatment-resistant depressions pose serious problems in mental health care. Mindfulness-based cognitive therapy (MBCT) is an effective treatment for remitted and currently depressed patients. It is, however, unknown whether MBCT is effective for chronic, treatment-resistant depressed patients., Method: A pragmatic, multicenter, randomized-controlled trial was conducted comparing treatment-as-usual (TAU) with MBCT + TAU in 106 chronically depressed outpatients who previously received pharmacotherapy (≥4 weeks) and psychological treatment (≥10 sessions)., Results: Based on the intention-to-treat (ITT) analysis, participants in the MBCT + TAU condition did not have significantly fewer depressive symptoms than those in the TAU condition (-3.23 [-6.99 to 0.54], d = 0.35, P = 0.09) at posttreatment. However, compared to TAU, the MBCT + TAU group reported significantly higher remission rates (χ 2 (2) = 4.25, φ = 0.22, P = 0.04), lower levels of rumination (-3.85 [-7.55 to -0.15], d = 0.39, P = 0.04), a higher quality of life (4.42 [0.03-8.81], d = 0.42, P = 0.048), more mindfulness skills (11.25 [6.09-16.40], d = 0.73, P < 0.001), and more self-compassion (2.91 [1.17-4.65], d = 0.64, P = 0.001). The percentage of non-completers in the MBCT + TAU condition was relatively high (n = 12, 24.5%). Per-protocol analyses revealed that those who completed MBCT + TAU had significantly fewer depressive symptoms at posttreatment compared to participants receiving TAU (-4.24 [-8.38 to -0.11], d = 0.45, P = 0.04)., Conclusion: Although the ITT analysis did not reveal a significant reduction in depressive symptoms of MBCT + TAU over TAU, MBCT + TAU seems to have beneficial effects for chronic, treatment-resistant depressed patients in terms of remission rates, rumination, quality of life, mindfulness skills, and self-compassion. Additionally, patients who completed MBCT showed significant reductions in depressive symptoms. Reasons for non-completion should be further investigated., (© 2018 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.)

Stressful life events, especially Childhood Trauma, predict ADHD symptoms. Childhood Trauma and negatively biased memory are risk factors for affective disorders. The association of life events and bias with ADHD symptoms may inform about the etiology of ADHD. Memory bias was tested using a computer task in N = 675 healthy adults. Life events and ADHD symptoms were assessed using questionnaires. The mediation of the association between life events and ADHD symptoms by memory bias was examined. We explored the roles of different types of life events and of ADHD symptom clusters. Life events and memory bias were associated with overall ADHD symptoms as well as inattention and hyperactivity/impulsivity symptom clusters. Memory bias mediated the association of Lifetime Life Events, specifically Childhood Trauma, with ADHD symptoms. Negatively biased memory may be a cognitive marker of the effects of Childhood Trauma on the development and/or persistence of ADHD symptoms.

Depression risk genes in combination with childhood events have been associated with biased processing as an intermediate phenotype for depression. The aim of the present conceptual replication study was to investigate the role of biased automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression, in the context of genes (5-HTTLPR polymorphism) and childhood trauma. A naturalistic remitted depressed patients sample (N = 209) performed an Approach-Avoidance Task (AAT) with facial expressions (angry, sad, happy and neutral). Childhood trauma was assessed with a questionnaire. Genotype groups were created based on allele frequency: LaLa versus S/Lg-carriers. The latter is associated with depression risk. We found that remitted S/Lg-carriers who experienced childhood trauma automatically avoided sad facial expressions relatively more than LaLa homozygotes with childhood trauma. Remitted LaLa-carriers who had not experienced childhood trauma, avoided sad faces relatively more than LaLa homozygotes with childhood trauma. We did not find a main effect of childhood trauma, nor differential avoidance of any of the other facial expressions. Although tentative, the results suggest that automatic approach-avoidance tendencies for disorder-congruent materials may be a fitting intermediate phenotype for depression. The specific pattern of tendencies, and the relation to depression, may depend on the genetic risk profile and childhood trauma, but replication is needed before firm conclusions can be drawn.

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

Cognitive models propose that both, negative interpretations of ambiguous social situations and ruminative thoughts about social events contribute to the maintenance of social anxiety disorder. It has further been postulated that ruminative thoughts fuel biased negative interpretations, however, evidence is rare. The present study used a multi-method approach to assess ruminative processing following a social interaction (post-event processing by self-report questionnaire and social rumination by experience sampling method) and negative interpretation bias (via two separate tasks) in a student sample (n = 51) screened for high (HSA) and low social anxiety (LSA). Results support the hypothesis that group differences in negative interpretations of ambiguous social situations in HSAs vs. LSAs are mediated by higher levels of post-event processing assessed in the questionnaire. Exploratory analyses highlight the potential role of comorbid depressive symptoms. The current findings help to advance the understanding of the association between two cognitive processes involved in social anxiety and stress the importance of ruminative post-event processing.

Background: Both childhood trauma and negative memory bias are associated with the onset and severity level of several psychiatric disorders, such as depression and anxiety disorders. Studies on these risk factors, however, generally use homogeneous noncomorbid samples. Hence, studies in naturalistic psychiatric samples are lacking. Moreover, we know little about the quantitative relationship between the frequency of traumatic childhood events, strength of memory bias and number of comorbid psychiatric disorders; the latter being an index of severity. The current study examined the association of childhood trauma and negative memory bias with psychopathology in a large naturalistic psychiatric patient sample., Methods: Frequency of traumatic childhood events (emotional neglect, psychological-, physical- and sexual abuse) was assessed using a questionnaire in a sample of 252 adult psychiatric patients with no psychotic or bipolar-I disorder and no cognitive disorder as main diagnosis. Patients were diagnosed for DSM-IV Axis-I and Axis-II disorders using a structured clinical interview. This allowed for the assessment of comorbidity between disorders. Negative memory bias for verbal stimuli was measured using a computer task., Results: Linear regression models revealed that the frequency of childhood trauma as well as negative memory bias was positively associated with psychiatric comorbidity, separately and above and beyond each other (all p  <   .01)., Conclusions: The results indicate that childhood trauma and negative memory bias may be of importance for a broader spectrum of psychiatric diagnoses, besides the frequently studied affective disorders. Importantly, frequently experiencing traumatic events during childhood increases the risk of comorbid psychiatric disorders.

Background and Objectives: Low self-esteem is a symptom of depression and depression vulnerability. Prior research on self-esteem has largely focused on implicit (ISE) and explicit self-esteem (ESE) as two separate constructs, missing their interaction. Therefore, the current study investigated the interaction between ISE and ESE in a depression-vulnerable group (remitted depressed patients; RDs), compared to never-depressed controls (ND)., Methods: Seventy-five RDs and 75 NDs participated in the study. To measure ESE, the Rosenberg Self-Esteem Scale (RSES) was used. The Implicit Association Test (IAT) and the Name Letter Preference Task (NLPT) were used to assess ISE., Results: RDs reported lower ESE than NDs. However, the two groups did not differ on ISE. RDs exhibited a damaged self-esteem or a low-congruent self-esteem, similar to what has been found in currently depressed patients. Moreover, damaged self-esteem was associated with residual depressive symptoms., Limitations: The results need to be interpreted with care because the IAT and NLPT did not reveal the same associations with the clinical measures., Conclusions: Implicit and explicit self-esteem may be different constructs in depression and studying the combination is important. The present study provides evidence indicating that damaged self-esteem may be more detrimental than low congruent self-esteem., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Theory implicates attentional bias (AB) or dysregulated attentional processing of emotional information in the recurrence of major depressive episodes. However, empirical study of AB among remitted depressed patients is limited in scope and has yielded mixed findings. Mixed findings may be accounted for by how the field has conceptualized and thereby studied AB. We propose that a novel temporal dynamic process perspective on AB may help disambiguate extant findings and elucidate the nature of AB in remitted depression. Thus, we reexamined Dot Probe data among remitted depressed patients (RMD; n = 328) and nondepressed controls (NDC; n = 82) that previously yielded null effects when AB was quantified by means of the traditional aggregated mean bias score (Vrijsen et al., 2014). We reanalyzed data using a novel computational approach that extracts a series of bias estimations from trial to trial (Zvielli, Bernstein, & Koster, 2015). Key features of these dynamic process signals revealed moderate to excellent reliability relative to the traditional aggregated mean bias scores. These features of AB dynamics-specifically temporal variability in AB including AB toward and away from emotional stimuli-were significantly elevated among RMDs relative to NDCs. Moreover, among RMDs, a greater number of past depressive episodes were associated with elevation in these features of AB dynamics. Effects were not accounted for by residual depressive symptoms or social anxiety symptoms. Findings indicate that dysregulation in attentional processing of emotional information reflected in AB dynamics may be key to depression vulnerability. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Cognitive Bias Modification (CBM) can yield clinically relevant results. Only few studies have directly manipulated memory bias, which is prominent in depression. In a new approach to CBM, we sought to simulate or oppose ruminative processes by training the retrieval of negative or positive words. Participants studied positive and negative word pairs (Swahili cues with Dutch translations). In the positive and negative conditions, each of the three study trials was followed by a cued-recall test of training-congruent translations; a no-practice condition merely studied the pairs. Recall of the translations was tested after the training and after 1 week. Both recall tests revealed evidence of training-congruent bias and bias was associated with emotional autobiographical memory. Positive retrieval practice yielded stable positive mood, in contrast to the other conditions. The results indicate that memory bias can be established through retrieval practice and that the bias transfers to mood and autobiographical memory., Competing Interests: Janna N. Vrijsen, Paula T. Hertel and Eni S. Becker declare that they have no conflict of interest. Informed Consent All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Animal Rights No animal studies were carried out by the authors for this article.