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Laboratory stress tasks are necessary to closely investigate the stress response in a controlled environment. However, to our knowledge, no study has tested whether participating in such tasks can pose any daily life adverse effect. Fifty-three healthy participants (46 women) took part in a laboratory session where stress was induced using a typical psychosocial stressor: the repeated Montreal Imaging Stress Task (rMIST). Average levels of negative affect (NA), heart rate (HR), root mean square of successive differences (RMSSD), and skin conductance level (SCL), as well as reactivity across all these parameters as measured with the experience sampling method (ESM) in the four days prior to the laboratory session were compared with the four days following the session. We also assessed whether vulnerability to psychopathology moderated these associations. Findings showed that the task did not pose any significant adverse effect on participants. However, there was an unexpected increase in average RMSSD and a decrease in average SCL pre- to post- task. In addition, more vulnerable individuals were more likely to experience an increase in average levels of NA in the days following the task compared to the days preceding it. Our findings suggest that laboratory stress tasks may pose a significant risk to more vulnerable individuals.

BackgroundAcceptance and commitment therapy (ACT) is promising in the treatment of early psychosis. Augmenting face-to-face ACT with mobile health ecological momentary interventions may increase its treatment effects and empower clients to take treatment into their own hands. ObjectiveThis study aimed to investigate and predict treatment engagement with and acceptability of acceptance and commitment therapy in daily life (ACT-DL), a novel ecological momentary intervention for people with an ultrahigh risk state and a first episode of psychosis. MethodsIn the multicenter randomized controlled trial, 148 individuals with ultrahigh risk or first-episode psychosis aged 15-65 years were randomized to treatment as usual only (control) or to ACT-DL combined with treatment as usual (experimental), consisting of 8 face-to-face sessions augmented with an ACT-based smartphone app, delivering ACT skills and techniques in daily life. For individuals in the intervention arm, we collected data on treatment engagement with and acceptability of ACT-DL during and after the intervention. Predictors of treatment engagement and acceptability included baseline demographic, clinical, and functional outcomes. ResultsParticipants who received ACT-DL in addition to treatment as usual (n=71) completed a mean of 6 (SD 3) sessions, with 59% (n=42) of participants completing all sessions. App engagement data (n=58) shows that, on a weekly basis, participants used the app 13 times and were compliant with 6 of 24 (25%) notifications. Distribution plots of debriefing scores (n=46) show that 85%-96% of participants reported usefulness on all acceptability items to at least some extent (scores ≥2; 1=no usefulness) and that 91% (n=42) of participants reported perceived burden by number and length of notifications (scores ≥2; 1=no burden). Multiple linear regression models were fitted to predict treatment engagement and acceptability. Ethnic minority backgrounds predicted lower notification response compliance (B=–4.37; P=.01), yet higher app usefulness (B=1.25; P=.049). Negative (B=–0.26; P=.01) and affective (B=0.14; P=.04) symptom severity predicted lower and higher ACT training usefulness, respectively. Being female (B=–1.03; P=.005) predicted lower usefulness of the ACT metaphor images on the app. ConclusionsOur results corroborate good treatment engagement with and acceptability of ACT-DL in early psychosis. We provide recommendations for future intervention optimization. Trial RegistrationOMON NL46439.068.13; https://onderzoekmetmensen.nl/en/trial/24803

Abstract Background Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users’ daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia). Methods In this hybrid effectiveness-implementation study, a parallel-group, assessor-blind, multi-centre cluster randomized controlled trial (cRCT) will be conducted, combined with a process and economic evaluation. In the cRCT, 24 clinical units (as the cluster and unit of randomization) at eight sites in four European countries will be randomly allocated using an unbalanced 2:1 ratio to one of two conditions: (a) the experimental condition, in which participants receive a Digital Mobile Mental Health intervention (DMMH) and other implementation strategies in addition to treatment as usual (TAU) or (b) the control condition, in which service users are provided with TAU. Outcome data in service users and clinicians will be collected at four time points: at baseline (t0), 2-month post-baseline (t1), 6-month post-baseline (t2), and 12-month post-baseline (t3). The primary outcome will be patient-reported service engagement assessed with the service attachment questionnaire at 2-month post-baseline. The process and economic evaluation will provide in-depth insights into in-vivo context-mechanism-outcome configurations and economic costs of the DMMH and other implementation strategies in routine care, respectively. Discussion If this trial provides evidence on reach, effectiveness, adoption, implementation and maintenance of implementing ESM-based monitoring, reporting, and feedback, it will form the basis for establishing its public health impact and has significant potential to bridge the research-to-practice gap and contribute to swifter ecological translation of digital innovations to real-world delivery in routine mental health care. Trial registration ISRCTN15109760 (ISRCTN registry, date: 03/08/2022).

Abstract Background Adolescent solitude was drastically impacted by the COVID-19 pandemic. As solitude is crucial for adolescent development through its association with both positive and negative developmental outcomes, it is critical to understand how adolescents’ daily-life solitary experiences changed as a result of the pandemic. Methods Using three waves of Experience Sampling Method data from a longitudinal study, we compared adolescents’ daily-life solitary experiences in the early (n T1 =100; M Age =16.1; SD Age =1.9; 93% girls) and mid-pandemic (n T2 =204; M Age =16.5; SD Age =2.0; 79% girls) to their pre-pandemic experiences. Results We found that adolescents with lower levels of pre-pandemic social support and social skills reported wanting to be alone less and feeling like an outsider more at both time points during the pandemic. In the mid-pandemic wave, adolescents with higher levels of pre-pandemic social support and social skills reported decreases in positive affect compared to the pre-pandemic wave. Conclusion This study shows that adolescents’ daily-life solitary experiences worsened throughout the COVID-19 pandemic. There should be continued concern for the wellbeing of all adolescents, not only those already at risk, as effects of the pandemic on mental health might only manifest later.

BackgroundPrevious mobile health (mHealth) studies have revealed significant links between depression and circadian rhythm features measured via wearables. However, the comprehensive impact of seasonal variations was not fully considered in these studies, potentially biasing interpretations in real-world settings. ObjectiveThis study aims to explore the associations between depression severity and wearable-measured circadian rhythms while accounting for seasonal impacts. MethodsData were sourced from a large longitudinal mHealth study, wherein participants’ depression severity was assessed biweekly using the 8-item Patient Health Questionnaire (PHQ-8), and participants’ behaviors, including sleep, step count, and heart rate (HR), were tracked via Fitbit devices for up to 2 years. We extracted 12 circadian rhythm features from the 14-day Fitbit data preceding each PHQ-8 assessment, including cosinor variables, such as HR peak timing (HR acrophase), and nonparametric features, such as the onset of the most active continuous 10-hour period (M10 onset). To investigate the association between depression severity and circadian rhythms while also assessing the seasonal impacts, we used three nested linear mixed-effects models for each circadian rhythm feature: (1) incorporating the PHQ-8 score as an independent variable, (2) adding seasonality, and (3) adding an interaction term between season and the PHQ-8 score. ResultsAnalyzing 10,018 PHQ-8 records alongside Fitbit data from 543 participants (n=414, 76.2% female; median age 48, IQR 32-58 years), we found that after adjusting for seasonal effects, higher PHQ-8 scores were associated with reduced daily steps (β=–93.61, P

BackgroundAs mobile health (mHealth) studies become increasingly productive owing to the advancements in wearable and mobile sensor technology, our ability to monitor and model human behavior will be constrained by participant receptivity. Many health constructs are dependent on subjective responses, and without such responses, researchers are left with little to no ground truth to accompany our ever-growing biobehavioral data. This issue can significantly impact the quality of a study, particularly for populations known to exhibit lower compliance rates. To address this challenge, researchers have proposed innovative approaches that use machine learning (ML) and sensor data to modify the timing and delivery of surveys. However, an overarching concern is the potential introduction of biases or unintended influences on participants’ responses when implementing new survey delivery methods. ObjectiveThis study aims to demonstrate the potential impact of an ML-based ecological momentary assessment (EMA) delivery system (using receptivity as the predictor variable) on the participants’ reported emotional state. We examine the factors that affect participants’ receptivity to EMAs in a 10-day wearable and EMA–based emotional state–sensing mHealth study. We study the physiological relationships indicative of receptivity and affect while also analyzing the interaction between the 2 constructs. MethodsWe collected data from 45 healthy participants wearing 2 devices measuring electrodermal activity, accelerometer, electrocardiography, and skin temperature while answering 10 EMAs daily, containing questions about perceived mood. Owing to the nature of our constructs, we can only obtain ground truth measures for both affect and receptivity during responses. Therefore, we used unsupervised and supervised ML methods to infer affect when a participant did not respond. Our unsupervised method used k-means clustering to determine the relationship between physiology and receptivity and then inferred the emotional state during nonresponses. For the supervised learning method, we primarily used random forest and neural networks to predict the affect of unlabeled data points as well as receptivity. ResultsOur findings showed that using a receptivity model to trigger EMAs decreased the reported negative affect by >3 points or 0.29 SDs in our self-reported affect measure, scored between 13 and 91. The findings also showed a bimodal distribution of our predicted affect during nonresponses. This indicates that this system initiates EMAs more commonly during states of higher positive emotions. ConclusionsOur results showed a clear relationship between affect and receptivity. This relationship can affect the efficacy of an mHealth study, particularly those that use an ML algorithm to trigger EMAs. Therefore, we propose that future work should focus on a smart trigger that promotes EMA receptivity without influencing affect during sampled time points.

Background: Research indicates that Acceptance and Commitment Therapy in Daily Life (ACT-DL) is effective in reducing symptoms of depression, anxiety and psychosis. During adolescence, vulnerability to psychopathology peaks, creating a window for early interventions, while white matter development is ongoing. This study aims to examine microstructural white matter after ACT-DL intervention in youngsters with mild psychopathology. Methods: Forty-five individuals with mild psychopathology were randomly allocated to ACT-DL (n=20) or topic discussion control (TD, n=25). Symptomatology was assessed with the Community Assessment of Psychic Experiences (CAPE), Montgomery–Åsberg Depression Rating Scale (MADRS) and the Experience Sampling Method (ESM). Diffusion Weighted Imaging (DWI) and network-connectivity parameters were obtained and compared before and after the intervention/control condition. Interactions between microstructural white matter change and condition were examined in models of CAPE positive symptoms and ESM subclinical psychotic experiences (PE) and negative affect (NA) levels. Results: ACT-DL, compared to TD, was associated with changes on subclinical depressive and psychotic symptom levels. There was no significant change in DWI or network connectivity in either condition and no significant difference between both conditions. In the model of NA, several regional interactions between condition and network measures were significant, but stratification per condition provided no significant associations. There were no significant interactions between DWI or network connectivity parameters and condition in the models of the CAPE positive symptoms, MADRS and PE. Conclusions: The findings suggest that behavioral (symptom) changes are more sensitive to a five-week psychological training than microstructural white matter changes which did not show significant changes over time.

BackgroundMental health problems occur in interactions in daily life. Yet, it is challenging to bring contextual information into the therapy room. The experience sampling method (ESM) may facilitate this by assessing clients’ thoughts, feelings, symptoms, and behaviors as they are experienced in everyday life. However, the ESM is still primarily used in research settings, with little uptake in clinical practice. One aspect that may facilitate clinical implementation concerns the use of ESM protocols, which involves providing practitioners with ready-to-use ESM questionnaires, sampling schemes, visualizations, and training. ObjectiveThis pilot study’s objective was to evaluate the usability of an ESM protocol for using the ESM in a specialized mental health care setting. MethodsWe created the ESM protocol using the m-Path software platform and tested its usability in clinical practice. The ESM protocol consists of a dashboard for practitioners (ie, including the setup of the template and data visualizations) and an app for clients (ie, for completing the ESM questionnaires). A total of 8 practitioners and 17 clients used the ESM in practice between December 1, 2020, and July 31, 2021. Usability was assessed using questionnaires, ESM compliance rates, and semistructured interviews. ResultsThe usability was overall rated reasonable to good by practitioners (mean scores of usability items ranging from 5.33, SD 0.91, to 6.06, SD 0.73, on a scale ranging from 1 to 7). However, practitioners expressed difficulty in personalizing the template and reported insufficient guidelines on how to use the ESM in clinical practice. On average, clients completed 55% (SD 25%) of the ESM questionnaires. They rated the usability as reasonable to good, but their scores were slightly lower and more variable than those of the practitioners (mean scores of usability items ranging from 4.18, SD 1.70, to 5.94, SD 1.50 on a scale ranging from 1 to 7). Clients also voiced several concerns over the piloted ESM template, with some indicating no interest in the continued use of the ESM. ConclusionsThe findings suggest that using an ESM protocol may facilitate the implementation of the ESM as a mobile health assessment tool in psychiatry. However, additional adaptions should be made before further implementation. Adaptions include providing training on personalizing questionnaires, adding additional sampling scheme formats as well as an open-text field, and creating a dynamic data visualization interface. Future studies should also identify factors determining the suitability of the ESM for specific treatment goals among different client populations.

BackgroundCross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low “stressor reactivity” [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. ObjectiveExtending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries. MethodsOver 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages. As (partly) preregistered, hypotheses were tested cross-sectionally at baseline (N=558), and longitudinally (n=200), using mixed effects models and mediation analyses. ResultsRFs at baseline, including positive appraisal style (PAS), optimism (OPT), general self-efficacy (GSE), perceived good stress recovery (REC), and perceived social support (PSS), were negatively associated with SR scores, not only cross-sectionally (baseline SR scores; all P

Abstract Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants’ study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants’ age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.

Background: The role of loneliness and social exclusion in the development of paranoia is largely unexplored. Negative affect may mediate potential associations between these factors. We investigated the temporal relationships of daily-life loneliness, felt social exclusion, negative affect, and paranoia across the psychosis continuum. Method: Seventy-five participants, including 29 individuals with a diagnosis of non-affective psychosis, 20 first-degree relatives, and 26 controls used an Experience Sampling Method (ESM) app to capture the fluctuations in loneliness, feelings of social exclusion, paranoia, and negative affect across a 1-week period. Data were analysed with multilevel regression analyses. Results: In all groups, loneliness and feelings of social exclusion were independent predictors of paranoia over time (b = 0.05, p

BackgroundMajor depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features. ObjectiveWe aimed to address these 3 challenges to inform future work in stratified analyses. MethodsUsing smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model. ResultsWe demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression. ConclusionsThis work contributes to our understanding of how these mobile health–derived features are associated with depression symptom severity to inform future work in stratified analyses.

BackgroundStress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. ObjectiveThis study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. MethodsIn a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net–based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. ResultsParticipant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. ConclusionsThe Dynamic Modelling of Resilience–Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. International Registered Report Identifier (IRRID)DERR1-10.2196/39817

BackgroundNonsuicidal self-injury (NSSI) is a major mental health concern. Despite increased research efforts on establishing the prevalence and correlates of the presence and severity of NSSI, we still lack basic knowledge of the course, predictors, and relationship of NSSI with other self-damaging behaviors in daily life. Such information will be helpful for better informing mental health professionals and allocating treatment resources. The DAILY (Detection of Acute rIsk of seLf-injurY) project will address these gaps among individuals seeking treatment. ObjectiveThis protocol paper presents the DAILY project’s aims, design, and materials used. The primary objectives are to advance understanding of (1) the short-term course and contexts of elevated risk for NSSI thoughts, urges, and behavior; (2) the transition from NSSI thoughts and urges to NSSI behavior; and (3) the association of NSSI with disordered eating, substance use, and suicidal thoughts and behaviors. A secondary aim is to evaluate the perspectives of individuals seeking treatment and mental health professionals regarding the feasibility, scope, and utility of digital self-monitoring and interventions that target NSSI in daily life. MethodsThe DAILY project is funded by the Research Foundation Flanders (Belgium). Data collection involves 3 phases: a baseline assessment (phase 1), 28 days of ecological momentary assessment (EMA) followed by a clinical session and feedback survey (phase 2), and 2 follow-up surveys and an optional interview (phase 3). The EMA protocol consists of regular EMA surveys (6 times per day), additional burst EMA surveys spaced at a higher frequency when experiencing intense NSSI urges (3 surveys within 30 minutes), and event registrations of NSSI behavior. The primary outcomes are NSSI thoughts, NSSI urges, self-efficacy to resist NSSI, and NSSI behavior, with disordered eating (restrictive eating, binge eating, and purging), substance use (binge drinking and smoking cannabis), and suicidal thoughts and behaviors surveyed as secondary outcomes. The assessed predictors include emotions, cognitions, contextual information, and social appraisals. ResultsWe will recruit approximately 120 individuals seeking treatment aged 15 to 39 years from mental health services across the Flanders region of Belgium. Recruitment began in June 2021 and data collection is anticipated to conclude in August 2023. ConclusionsThe findings of the DAILY project will provide a detailed characterization of the short-term course and patterns of risk for NSSI and advance understanding of how, why, and when NSSI and other self-damaging behaviors unfold among individuals seeking treatment. This will inform clinical practice and provide the scientific building blocks for novel intervention approaches outside of the therapy room that support people who self-injure in real time. International Registered Report Identifier (IRRID)DERR1-10.2196/46244

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Abstract Background Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data. Methods Remote Assessment of Disease and Relapse – Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse – Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months. Results Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types. Conclusions RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.

BackgroundRemote measurement technologies (RMTs) have the potential to revolutionize major depressive disorder (MDD) disease management by offering the ability to assess, monitor, and predict symptom changes. However, the promise of RMT data depends heavily on sustained user engagement over extended periods. In this paper, we report a longitudinal qualitative study of the subjective experience of people with MDD engaging with RMTs to provide insight into system usability and user experience and to provide the basis for future promotion of RMT use in research and clinical practice. ObjectiveWe aimed to understand the subjective experience of long-term engagement with RMTs using qualitative data collected in a longitudinal study of RMTs for monitoring MDD. The objectives were to explore the key themes associated with long-term RMT use and to identify recommendations for future system engagement. MethodsIn this multisite, longitudinal qualitative research study, 124 semistructured interviews were conducted with 99 participants across the United Kingdom, Spain, and the Netherlands at 3-month, 12-month, and 24-month time points during a study exploring RMT use (the Remote Assessment of Disease and Relapse-Major Depressive Disorder study). Data were analyzed using thematic analysis, and interviews were audio recorded, transcribed, and coded in the native language, with the resulting quotes translated into English. ResultsThere were 5 main themes regarding the subjective experience of long-term RMT use: research-related factors, the utility of RMTs for self-management, technology-related factors, clinical factors, and system amendments and additions. ConclusionsThe subjective experience of long-term RMT use can be considered from 2 main perspectives: experiential factors (how participants construct their experience of engaging with RMTs) and system-related factors (direct engagement with the technologies). A set of recommendations based on these strands are proposed for both future research and the real-world implementation of RMTs into clinical practice. Future exploration of experiential engagement with RMTs will be key to the successful use of RMTs in clinical care.

BackgroundIdentifying momentary risk and protective mechanisms may enhance our understanding and treatment of mental disorders. Affective stress reactivity is one mechanism that has been reported to be altered in individuals with early and later stages of mental disorder. Additionally, initial evidence suggests individuals with early and enduring psychosis may have an extended recovery period of negative affect in response to daily stressors (ie, a longer duration until affect reaches baseline levels after stress), but evidence on positive affective recovery as a putative protective mechanism remains limited. ObjectiveThis study aimed to investigate trajectories of positive affect in response to stress across the continuum of mental disorder in a transdiagnostic sample. MethodsUsing the Experience Sampling Method, minor activity-, event-, and overall stress and positive affect were assessed 10 times a day, with time points approximately 90 minutes apart on six consecutive days in a pooled data set including 367 individuals with a mental disorder, 217 individuals at risk for a severe mental disorder, and 227 controls. Multilevel analysis and linear contrasts were used to investigate trajectories of positive affect within and between groups. ResultsBaseline positive affect differed across groups, and we observed stress reactivity in positive affect within each group. We found evidence for positive affective recovery after reporting activity- or overall stress within each group. While controls recovered to baseline positive affect about 90 minutes after stress, patients and at-risk individuals required about 180 minutes to recover. However, between-group differences in the affective recovery period fell short of significance (all P>.05). ConclusionsThe results provide first evidence that positive affective recovery may be relevant within transdiagnostic subclinical and clinical stages of mental disorder, suggesting that it may be a potential target for mobile health interventions fostering resilience in daily life.

BackgroundGait is an essential manifestation of depression. However, the gait characteristics of daily walking and their relationships with depression have yet to be fully explored. ObjectiveThe aim of this study was to explore associations between depression symptom severity and daily-life gait characteristics derived from acceleration signals in real-world settings. MethodsWe used two ambulatory data sets (N=71 and N=215) with acceleration signals collected by wearable devices and mobile phones, respectively. We extracted 12 daily-life gait features to describe the distribution and variance of gait cadence and force over a long-term period. Spearman coefficients and linear mixed-effects models were used to explore the associations between daily-life gait features and depression symptom severity measured by the 15-item Geriatric Depression Scale (GDS-15) and 8-item Patient Health Questionnaire (PHQ-8) self-reported questionnaires. The likelihood-ratio (LR) test was used to test whether daily-life gait features could provide additional information relative to the laboratory gait features. ResultsHigher depression symptom severity was significantly associated with lower gait cadence of high-performance walking (segments with faster walking speed) over a long-term period in both data sets. The linear regression model with long-term daily-life gait features (R2=0.30) fitted depression scores significantly better (LR test P=.001) than the model with only laboratory gait features (R2=0.06). ConclusionsThis study indicated that the significant links between daily-life walking characteristics and depression symptom severity could be captured by both wearable devices and mobile phones. The daily-life gait patterns could provide additional information for predicting depression symptom severity relative to laboratory walking. These findings may contribute to developing clinical tools to remotely monitor mental health in real-world settings.

Abstract Background The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a clinical illness Covid-19, has had a major impact on mental health globally. Those diagnosed with major depressive disorder (MDD) may be negatively impacted by the global pandemic due to social isolation, feelings of loneliness or lack of access to care. This study seeks to assess the impact of the 1st lockdown – pre-, during and post – in adults with a recent history of MDD across multiple centres. Methods This study is a secondary analysis of an on-going cohort study, RADAR-MDD project, a multi-centre study examining the use of remote measurement technology (RMT) in monitoring MDD. Self-reported questionnaire and passive data streams were analysed from participants who had joined the project prior to 1st December 2019 and had completed Patient Health and Self-esteem Questionnaires during the pandemic (n = 252). We used mixed models for repeated measures to estimate trajectories of depressive symptoms, self-esteem, and sleep duration. Results In our sample of 252 participants, 48% (n = 121) had clinically relevant depressive symptoms shortly before the pandemic. For the sample as a whole, we found no evidence that depressive symptoms or self-esteem changed between pre-, during- and post-lockdown. However, we found evidence that mean sleep duration (in minutes) decreased significantly between during- and post- lockdown (− 12.16; 95% CI − 18.39 to − 5.92; p

Reduced positive future thinking has been associated with suicidal ideation and behavior in adults, and appears to be exacerbated by negative affect. Yet, this has received little attention in youth. Prior research has also focused on longer-term future thinking, e.g., months and years, and relied on lab-based assessments. Using the experience sampling method (ESM), we investigated whether short-term future thinking in daily life was associated with suicidal ideation in youth and explored the role of affect in the future thinking–suicidal ideation relationship. A community sample of N = 722 adolescent twins and their non-twin siblings completed ESM as part of the TwinssCan study (n = 55 with, and n = 667 without, past-week suicidal ideation). Participants completed self-report questionnaires, including on past-week suicidal ideation as part of the SCL-90. Subsequently, daily future thinking was assessed each morning for six days with ESM. To investigate the relationship between daily positive future thinking and past-week suicidal ideation, we estimated a mixed-effects linear regression model with a random intercept for participant, including age and sex as covariates. The relationship between daily positive future thinking, past-week suicidal ideation, and average positive and negative affect from the previous day was investigated by estimating two separate mixed-effects linear regression models (one for negative affect, one for positive affect), with a random intercept for participant, and random slopes for average positive and negative affect. Our results showed that participants reporting higher past-week suicidal ideation also reported significantly less daily positive future thinking during the ESM period, and this association remained significant when controlling for previous-day average positive and negative affect. Higher average positive affect from the previous day was significantly associated with higher positive future thinking. Although average negative affect from the previous day was associated with lower positive future thinking, this association was not statistically significant. Our findings indicate that short-term future thinking relates to suicidal ideation among a non-clinical sample of adolescents. Future research should investigate the directionality of the future thinking–suicidal ideation relationship, in order to investigate whether impaired future thinking may be an early warning signal for escalating suicidal ideation in youth.

Abstract Background AVATAR therapy is a novel intervention targeting distressing auditory verbal hallucinations (henceforth ‘voices’). A digital simulation (avatar) of the voice is created and used in a three-way dialogue between participant, avatar and therapist. To date, therapy has been delivered over 6 sessions, comprising an initial phase, focusing on standing up to a hostile avatar, and a second phase in which the avatar concedes and focus shifts to individualised treatment targets, including beliefs about voices. The first fully powered randomised trial found AVATAR therapy resulted in a rapid and substantial fall in voice frequency and associated distress that was superior to supportive counselling at 12 weeks. The main objective of this AVATAR2 trial is to test the efficacy of two forms of AVATAR therapy in reducing voice-related distress: AVATAR-brief (standardised focus on exposure, assertiveness and self-esteem) and AVATAR-extended (phase 1 mirroring AVATAR-brief augmented by a formulation-driven phase 2). Secondary objectives include the examination of additional voice, wellbeing and mood outcomes, the exploration of mediators and moderators of therapy response, and examining cost-effectiveness of both forms of therapy compared with usual treatment (TAU). Methods This multi-site parallel group randomised controlled trial will independently randomise 345 individuals to receive AVATAR-brief (6 sessions) plus TAU or AVATAR-extended (12 sessions) plus TAU or TAU alone (1:1:1 allocation). Participants will be people with a diagnosis of schizophrenia spectrum and other psychotic disorders who have heard distressing voices for more than 6 months. The primary outcome is the PSYRATS Auditory Hallucinations Distress dimension score at 16 and 28 weeks, conducted by blinded assessors. Statistical analysis will follow the intention-to-treat principle and data will be analysed using linear mixed models. Mediation and moderation analyses using contemporary causal inference methods will be conducted as secondary analyses. Service costs will be calculated, and cost-effectiveness assessed in terms of quality-adjusted life years accrued. Discussion This study will clarify optimal therapy delivery, test efficacy in a multi-site study and enable the testing of the AVATAR software platform, therapy training and provision in NHS settings. Trial registration ISRCTN registry ISRCTN55682735 . Registered on 22 January 2020. The trial is funded by the Wellcome Trust (WT).

Abstract The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p

Purpose: Early detection and intervention of mental health problems in youth are topical given that mental disorders often start early in life. Young people with emerging mental disorders however, often present with non-specific, fluctuating symptoms. Recent reports indicate a decline in social functioning (SF) as an early sign of specific emerging mental disorders such as depression or anxiety, making SF a favorable transdiagnostic approach for earlier detection and intervention. Our aim was to investigate the value of SF in relation to transdiagnostic symptoms, and as a predictor of psychopathology over time, while exploring traditional retrospective versus innovative daily diary measurements of SF in youth. Method: Participants (N = 75) were 16–25 years of age and presented early stage psychiatric symptomatology. Psychiatric symptoms, including anxiety and depression, as well as SF -both in retrospect and in daily life- were assessed at two time points and analyzed cross-sectionally and longitudinally. Results: A significant and negative association between SF and all psychiatric symptoms was found, and SF was a significant predictor of change in general psychiatric symptoms over time. Results were only significant when SF was measured traditionally retrospective. Conclusion: This study confirms a distinct relation between SF and transdiagnostic psychiatric symptoms in youth, even in a (sub)clinical population, and points towards SF as a predictor of transdiagnostic psychiatric symptoms. Further research is needed to learn more about the added value of daily life versus retrospective measurements.

Abstract Background 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with an increased risk of psychiatric disorders. Vulnerability for psychopathology has been related to an increased reactivity to stress. Here, we examined affective states, perceived stress, affective and psychotic reactivity to various sources of environmental stress using the experience sampling method (ESM), a structured diary technique allowing repeated assessments in the context of daily life. Methods Adults with 22q11DS (n = 31; age, 34.1 years) and matched healthy controls (HCs; n = 24; age, 39.9 years) were included. ESM was used to assess affective states, perceived stress, and stress reactivity. Data were analyzed using multilevel regression models. Results Adults with 22q11DS displayed overall higher levels of negative affect but comparable levels of positive affect compared to HCs. Higher levels of perceived stress were reported by individuals with 22q11DS. Comparable affective and psychotic reactivity in relation to all types of environmental stress was observed between the two groups. Conclusion The results point toward higher levels of negative affect and differences in the perception of daily hassles in 22q11DS but no difference in affective or psychotic reactivity to stress. This study contributes to the growing literature regarding the impact of stress on the development of psychopathology in the 22q11DS population.

BackgroundThe mobility of an individual measured by phone-collected location data has been found to be associated with depression; however, the longitudinal relationships (the temporal direction of relationships) between depressive symptom severity and phone-measured mobility have yet to be fully explored. ObjectiveWe aimed to explore the relationships and the direction of the relationships between depressive symptom severity and phone-measured mobility over time. MethodsData used in this paper came from a major EU program, called the Remote Assessment of Disease and Relapse–Major Depressive Disorder, which was conducted in 3 European countries. Depressive symptom severity was measured with the 8-item Patient Health Questionnaire (PHQ-8) through mobile phones every 2 weeks. Participants’ location data were recorded by GPS and network sensors in mobile phones every 10 minutes, and 11 mobility features were extracted from location data for the 2 weeks prior to the PHQ-8 assessment. Dynamic structural equation modeling was used to explore the longitudinal relationships between depressive symptom severity and phone-measured mobility. ResultsThis study included 2341 PHQ-8 records and corresponding phone-collected location data from 290 participants (age: median 50.0 IQR 34.0, 59.0) years; of whom 215 (74.1%) were female, and 149 (51.4%) were employed. Significant negative correlations were found between depressive symptom severity and phone-measured mobility, and these correlations were more significant at the within-individual level than the between-individual level. For the direction of relationships over time, Homestay (time at home) (φ=0.09, P=.01), Location Entropy (time distribution on different locations) (φ=−0.04, P=.02), and Residential Location Count (reflecting traveling) (φ=0.05, P=.02) were significantly correlated with the subsequent changes in the PHQ-8 score, while changes in the PHQ-8 score significantly affected (φ=−0.07, P

BackgroundNegative symptoms occur in individuals at ultrahigh risk (UHR) for psychosis. Although there is evidence that observer ratings of negative symptoms are associated with level of functioning, the predictive value of subjective experience in daily life for individuals at UHR has not been studied yet. ObjectiveThis study therefore aims to investigate the predictive value of momentary manifestations of negative symptoms for clinical outcomes in individuals at UHR. MethodsExperience sampling methodology was used to measure momentary manifestations of negative symptoms (blunted affective experience, lack of social drive, anhedonia, and social anhedonia) in the daily lives of 79 individuals at UHR. Clinical outcomes (level of functioning, illness severity, UHR status, and transition status) were assessed at baseline and at 1- and 2-year follow-ups. ResultsLack of social drive, operationalized as greater experienced pleasantness of being alone, was associated with poorer functioning at the 2-year follow-up (b=−4.62, P=.01). Higher levels of anhedonia were associated with poorer functioning at the 1-year follow-up (b=5.61, P=.02). Higher levels of social anhedonia were associated with poorer functioning (eg, disability subscale: b=6.36, P=.006) and greater illness severity (b=−0.38, P=.045) at the 1-year follow-up. In exploratory analyses, there was evidence that individuals with greater variability of positive affect (used as a measure of blunted affective experience) experienced a shorter time to remission from UHR status at follow-up (hazard ratio=4.93, P=.005). ConclusionsTargeting negative symptoms in individuals at UHR may help to predict clinical outcomes and may be a promising target for interventions in the early stages of psychosis.

Adolescence is a vulnerable period for psychopathology development, and certain parenting styles are consistent and robust predictors of a broad range of mental health outcomes. The mechanisms through which maladaptive parenting styles affect the development of psychopathology are assumed to be largely social in nature. Yet, the social mechanisms linking parenting to psychopathology are unexplored at arguably the most important level of functioning: daily life. This study aims to identify the associations between three parenting styles, and the experience of daily-life social interactions. Furthermore, we aim to explore the extent to which these parenting styles and altered daily-life social experiences are associated with psychopathology. In this study, we recruited a sample of N = 1,913 adolescents (63.3% girls; mean age = 13.7, age range = 11 to 20) as part of the first wave of the longitudinal cohort study “SIGMA”. Parenting styles (psychological control, responsiveness, and autonomy support) and psychopathology symptoms were assessed using a retrospective questionnaire battery. The experienced quality of social interactions in different types of company was assessed using the experience sampling method, ten times per day for 6 days. Direct associations between parenting styles and general quality of daily-life social experiences were tested using a three-level linear model, revealing significant associations between social experiences and different parenting styles. When interaction effects were added to this model, we found that maternal responsiveness and paternal psychological control mainly related to altered qualities of social interactions with parents, while paternal autonomy support was associated with better experiences of non-family social interactions. Finally, an exploratory path analysis highlighted how both paternal autonomy support and altered quality of non-family interactions are uniquely associated with psychopathology levels. These findings demonstrate the general and pervasive effects of maladaptive parenting styles, as parenting seems to broadly affect adolescents' interactions with different types of social partners in everyday life. Moreover, they illustrate a potential mediated relationship in which altered daily-life social interactions could drive the development of psychopathology. A stronger focus may be required on the role of altered day-to-day social experiences in the prevention and potentially, the treatment, of adolescent psychopathology.

BackgroundResearch in mental health has found associations between depression and individuals’ behaviors and statuses, such as social connections and interactions, working status, mobility, and social isolation and loneliness. These behaviors and statuses can be approximated by the nearby Bluetooth device count (NBDC) detected by Bluetooth sensors in mobile phones. ObjectiveThis study aimed to explore the value of the NBDC data in predicting depressive symptom severity as measured via the 8-item Patient Health Questionnaire (PHQ-8). MethodsThe data used in this paper included 2886 biweekly PHQ-8 records collected from 316 participants recruited from three study sites in the Netherlands, Spain, and the United Kingdom as part of the EU Remote Assessment of Disease and Relapse-Central Nervous System (RADAR-CNS) study. From the NBDC data 2 weeks prior to each PHQ-8 score, we extracted 49 Bluetooth features, including statistical features and nonlinear features for measuring the periodicity and regularity of individuals’ life rhythms. Linear mixed-effect models were used to explore associations between Bluetooth features and the PHQ-8 score. We then applied hierarchical Bayesian linear regression models to predict the PHQ-8 score from the extracted Bluetooth features. ResultsA number of significant associations were found between Bluetooth features and depressive symptom severity. Generally speaking, along with depressive symptom worsening, one or more of the following changes were found in the preceding 2 weeks of the NBDC data: (1) the amount decreased, (2) the variance decreased, (3) the periodicity (especially the circadian rhythm) decreased, and (4) the NBDC sequence became more irregular. Compared with commonly used machine learning models, the proposed hierarchical Bayesian linear regression model achieved the best prediction metrics (R2=0.526) and a root mean squared error (RMSE) of 3.891. Bluetooth features can explain an extra 18.8% of the variance in the PHQ-8 score relative to the baseline model without Bluetooth features (R2=0.338, RMSE=4.547). ConclusionsOur statistical results indicate that the NBDC data have the potential to reflect changes in individuals’ behaviors and statuses concurrent with the changes in the depressive state. The prediction results demonstrate that the NBDC data have a significant value in predicting depressive symptom severity. These findings may have utility for the mental health monitoring practice in real-world settings.

Abstract Background Psychotic experiences, social functioning and general psychopathology are important targets for early intervention in individuals with Ultra-High-Risk state (UHR) and a first-episode psychosis (FEP). Acceptance and Commitment Therapy (ACT) is a promising, next-generation Cognitive Behavioural Therapy (CBT) that aims to modify these targets, but evidence on sustainable change and its underlying mechanisms in individuals’ daily lives remains limited. The aim of the INTERACT study is to investigate the efficacy of a novel ecological momentary intervention, Acceptance and Commitment Therapy in Daily Life (ACT-DL) in a multi-centre randomised controlled trial of individuals with UHR or FEP. Methods/design In a multi-centre randomised controlled trial, individuals aged 16–65 years with UHR or FEP will be randomly allocated to ACT-DL in addition to treatment as usual (TAU) as the experimental condition or a control condition of TAU only, which will include – for the entire study period – access to routine mental health care and, where applicable, CBT for psychosis (CBTp). Outcomes will be assessed at baseline (i.e. before randomisation), post-intervention (i.e. after the 8-week intervention period), and 6-month and 12-month follow-ups (i.e. 6 and 12 months after completing the intervention period) by blinded assessors. The primary outcome will be distress associated with psychotic experiences, while secondary outcomes will include (momentary) psychotic experiences, social functioning and psychopathology. Process measures to assess putative mechanisms of change will include psychological flexibility, stress sensitivity and reward experiences. In addition, acceptability, treatment adherence and treatment fidelity of ACT-DL will be assessed. Discussion The current study is the first to test the efficacy of ACT-DL in individuals with UHR and FEP. If this trial demonstrates the efficacy of ACT-DL, it has the potential to significantly advance the treatment of people with UHR and FEP and, more generally, provides initial support for implementing mHealth interventions in mental health services. Trial registration Netherlands Trial Register, ID: NTR4252. Registered on 26 September 2013.

Delayed responses are a common phenomenon in experience sampling studies. Yet no consensus exists on whether they should be excluded from the analysis or what the threshold for exclusion should be. Delayed responses could introduce bias, but previous investigations of systematic differences between delayed and timely responses have offered unclear results. To investigate differences as a function of delay, we conducted secondary analyses of nine paper and pencil based experience sampling studies including 1,528 individuals with different clinical statuses. In all participants, there were significant decreases in positive and increases in negative affect as a function of delay. In addition, delayed answers of participants without depression showed higher within-person variability and an initial strengthening in the relationships between contextual stress and affect. Participants with depression mostly showed the opposite pattern. Delayed responses seem qualitatively different from timely responses. Further research is needed to understand the mechanisms underlying these differences.

Background Stress plays an important role in the development of mental illness, and an increasing number of studies is trying to detect moments of perceived stress in everyday life based on physiological data gathered using ambulatory devices. However, based on laboratory studies, there is only modest evidence for a relationship between self-reported stress and physiological ambulatory measures. This descriptive systematic review evaluates the evidence for studies investigating an association between self-reported stress and physiological measures under daily life conditions. Methods Three databases were searched for articles assessing an association between self-reported stress and cardiovascular and skin conductance measures simultaneously over the course of at least a day. Results We reviewed findings of 36 studies investigating an association between self-reported stress and cardiovascular measures with overall 135 analyses of associations between self-reported stress and cardiovascular measures. Overall, 35% of all analyses showed a significant or marginally significant association in the expected direction. The most consistent results were found for perceived stress, high-arousal negative affect scales, and event-related self-reported stress measures, and for frequency-domain heart rate variability physiological measures. There was much heterogeneity in measures and methods. Conclusion These findings confirm that daily-life stress-dynamics are complex and require a better understanding. Choices in design and measurement seem to play a role. We provide some guidance for future studies.

IntroductionAlthough research over the past decade has resulted in significantly increased knowledge about distal risk factors for non-suicidal self-injury (NSSI), little is known about short-term (proximal) factors that predict NSSI thoughts and behaviors. Drawing on contemporaneous theories of NSSI, as well as the concept of ideation-to-action, the present study clarifies (a) real-time factors that predict NSSI thoughts and (b) the extent to which theoretically important momentary factors (i.e., negative affect, positive affect, and self-efficacy to resist NSSI) predict NSSI behavior in daily life, beyond NSSI thoughts.MethodsUsing experience sampling methodology, intensive longitudinal data was obtained from 30 young adults with frequent NSSI episodes in the last year. Participants completed assessments up to eight times per day for 12 consecutive days (signal-contingent sampling). This resulted in the collection of 2,222 assessments (median compliance = 79.2%) during which 591 NSSI thoughts and 270 NSSI behaviors were recorded. Using the dynamic structural equation modeling framework, multilevel vector autoregressive models were constructed.ResultsWithin the same assessment, negative affect was positively associated with NSSI thoughts, whereas positive affect and self-efficacy to resist NSSI were each negatively associated with NSSI thoughts. Across assessments, higher-than-usual negative affect and self-efficacy to resist NSSI were predictive of short-term change in NSSI thoughts. While fluctuations in both negative affect and positive affect prospectively predicted NSSI behavior, these factors became non-significant in models that controlled for the predictive effect of NSSI thoughts. In contrast, self-efficacy to resist NSSI incrementally predicted a lower probability of engaging in NSSI, above and beyond NSSI thoughts.DiscussionThis study provides preliminary evidence that affective fluctuations may uniquely predict NSSI thoughts but not NSSI behaviors, and point to the role of personal belief in the ability to resist NSSI in preventing NSSI behavior. These findings illustrate the need to differentiate between the development of NSSI thoughts and the progression from NSSI thoughts to behavior, as these are likely distinct processes, with different predictors.

Abstract Background Due to a number of methodological advantages and theoretical considerations, more and more studies in clinical psychology research employ the Experience Sampling Method (ESM) as a data collection technique. Despite this growing interest, the absence of methodological guidelines related to the use of ESM has resulted in a large heterogeneity of designs while the potential effects of the design itself on the response behavior of the participants remain unknown. The objectives of this systematic review are to investigate the associations between the design characteristics and the data quality and feasibility of studies relying on ESM in severe psychiatric disorders. Methods We will search for all published studies using ambulatory assessment with patients suffering from major depressive disorder, bipolar disorder, and psychotic disorder or individuals at high risk for these disorders. Electronic database searches will be performed in PubMed and Web of Science with no restriction on the publication date. Two reviewers will independently screen original studies in a title/abstract phase and a full-text phase based on the inclusion criteria. The information related to the design and sample characteristics, data quality, and feasibility will be extracted. We will provide results in terms of a descriptive synthesis, and when applicable, a meta-analysis of the findings will be conducted. Discussion Our results will attempt to highlight how the feasibility and data quality of ambulatory assessment might be related to the methodological characteristics of the study designs in severe psychiatric disorders. We will discuss these associations in different subsamples if sufficient data are available and will examine limitations in the reporting of the methods of ambulatory studies in the current literature. Systematic review registration The protocol for this systematic review was registered on PROSPERO (PROSPERO 2017: CRD42017060322 ) and is available in full on the University of York website ( http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017060322 ).

Caregivers differ in their emotional response when facing difficult situations during the caregiving process. Individual differences in vulnerabilities and resources could play an exacerbating or buffering role in caregivers' reactivity to daily life stress. This study examines which caregiver characteristics modify emotional stress reactivity in dementia caregivers.Thirty caregivers collected momentary data, as based on the experience sampling methodology, to assess (1) appraised subjective stress related to events and minor disturbances in daily life, and (2) emotional reactivity to these daily life stressors, conceptualized as changes in negative affect. Caregiver characteristics (i.e. vulnerabilities and resources) were administered retrospectively.Caregivers who more frequently used the coping strategies 'seeking distraction', 'seeking social support', and 'fostering reassuring thoughts' experienced less emotional reactivity towards stressful daily events. A higher educational level and a higher sense of competence and mastery lowered emotional reactivity towards minor disturbances in daily life. No effects were found for age, gender, and hours of care and contact with the person with dementia.Caregiver resources can impact emotional reactivity to daily life stress. Interventions aimed at empowerment of caregiver resources, such as sense of competence, mastery, and coping, could help to reduce stress reactivity in dementia caregivers.

Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0-11 years) and late (12-18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis.

BACKGROUND:There is increasing interest in elucidating the association of different childhood adversities with psychosis-spectrum symptoms as well as the mechanistic processes involved. This study used experience sampling methodology to examine (i) associations of a range of childhood adversities with psychosis symptom domains in daily life; (ii) whether associations of abuse and neglect with symptoms are consistent across self-report and interview methods of trauma assessment; and (iii) the role of different adversities in moderating affective, psychotic-like, and paranoid reactivity to situational and social stressors. METHOD:A total of 206 nonclinical young adults were administered self-report and interview measures to assess childhood abuse, neglect, bullying, losses, and general traumatic events. Participants received personal digital assistants that signaled them randomly eight times daily for one week to complete questionnaires about current experiences, including symptoms, affect, and stress. RESULTS:Self-reported and interview-based abuse and neglect were associated with psychotic-like and paranoid symptoms, whereas only self-reported neglect was associated with negative-like symptoms. Bullying was associated with psychotic-like symptoms. Losses and general traumatic events were not directly associated with any of the symptom domains. All the childhood adversities were associated with stress reactivity in daily life. Interpersonal adversities (abuse, neglect, bullying, and losses) moderated psychotic-like and/or paranoid reactivity to situational and social stressors, whereas general traumatic events moderated psychotic-like reactivity to situational stress. Also, different interpersonal adversities exacerbated psychotic-like and/or paranoid symptoms in response to distinct social stressors. DISCUSSION:The present study provides a unique examination of how childhood adversities impact the expression of spectrum symptoms in the real world and lends support to the notion that stress reactivity is a mechanism implicated in the experience of reality distortion in individuals exposed to childhood trauma. Investigating the interplay between childhood experience and current context is relevant for uncovering potential pathways to the extended psychosis phenotype.

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.

Positive affect (PA) plays a crucial role in the development, course, and recovery of depression. Recently, we showed that a therapeutic application of the experience sampling method (ESM), consisting of feedback focusing on PA in daily life, was associated with a decrease in depressive symptoms. The present study investigated whether the experience of PA increased during the course of this intervention.Multicentre parallel randomized controlled trial. An electronic random sequence generator was used to allocate treatments.University, two local mental health care institutions, one local hospital.102 pharmacologically treated outpatients with a DSM-IV diagnosis of major depressive disorder, randomized over three treatment arms.Six weeks of ESM self-monitoring combined with weekly PA-focused feedback sessions (experimental group); six weeks of ESM self-monitoring combined with six weekly sessions without feedback (pseudo-experimental group); or treatment as usual (control group).The interaction between treatment allocation and time in predicting positive and negative affect (NA) was investigated in multilevel regression models.102 patients were randomized (mean age 48.0, SD 10.2) of which 81 finished the entire study protocol. All 102 patients were included in the analyses. The experimental group did not show a significant larger increase in momentary PA during or shortly after the intervention compared to the pseudo-experimental or control groups (χ2(2) = 0.33, p = .846). The pseudo-experimental group showed a larger decrease in NA compared to the control group (χ2(1) = 6.29, p =.012).PA-focused feedback did not significantly impact daily life PA during or shortly after the intervention. As the previously reported reduction in depressive symptoms associated with the feedback unveiled itself only after weeks, it is conceivable that the effects on daily life PA also evolve slowly and therefore were not captured by the experience sampling procedure immediately after treatment.Trialregister.nl/trialreg/index.asp. NTR1974.

BackgroundThe psychometric properties of an online test are not necessarily identical to its paper and pencil original. The aim of this study is to test whether the factor structure of the Community Assessment of Psychic Experiences (CAPE) is measurement invariant with respect to online vs. paper and pencil assessment.MethodThe factor structure of CAPE items assessed by paper and pencil (N = 796) was compared with the factor structure of CAPE items assessed by the Internet (N = 21,590) using formal tests for Measurement Invariance (MI). The effect size was calculated by estimating the Signed Item Difference in the Sample (SIDS) index and the Signed Test Difference in the Sample (STDS) for a hypothetical subject who scores 2 standard deviations above average on the latent dimensions.ResultsThe more restricted Metric Invariance model showed a significantly worse fit compared to the less restricted Configural Invariance model (χ(2)(23) = 152.75, pConclusionsOur findings did not support measurement invariance with respect to assessment method. Because of the small effect sizes, the measurement differences between the online assessed CAPE and its paper and pencil original can be neglected without major consequences for research purposes. However, a person with a high vulnerability for psychotic symptoms would score 4.80 points lower on the total scale if the CAPE is assessed online compared to paper and pencil assessment. Therefore, for clinical purposes, one should be cautious with online assessment of the CAPE.

In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs) associated with the stress response, such as FK506-binding protein 5 (FKBP5) and brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target underlying these interactions. Therefore, more detailed modelling of these effects, using appropriate covariates, is required. We examined whether BDNF/FKBP5 and childhood trauma interactions affected two proxies of hippocampal integrity: (i) hippocampal volume and (ii) cognitive performance on a block design (BD) and delayed auditory verbal task (AVLT). We also investigated whether the putative interaction was different for patients with a psychotic disorder (n = 89) compared to their non-psychotic siblings (n = 95), in order to elicit possible group-specific protective/vulnerability effects. SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5) and rs6265 (BDNF). In the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not different for patients and siblings. The omission of drug use and alcohol consumption sometimes yielded false positives, greatly affected explained error and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by childhood trauma interactions on assessments of hippocampal integrity suggests that the effect of these interactions on psychotic symptoms is not mediated by hippocampal integrity. The importance of appropriate statistical designs and inclusion of relevant covariates should be carefully considered.

Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.

INTRODUCTION: Stigma is an important environmental risk factor for a variety of outcomes in schizophrenia. In order to understand and remediate its effects, research is required to assess how stigma experiences are processed at the level of the individual. To this end, stereotype awareness (SA) with respect to people with mental illness and their families was explored in persons with psychotic disorder. METHOD: Data from the Dutch Genetic Risk and OUtcome of Psychosis project (GROUP) were analyzed. SA was measured using scales that assess a respondent's perception of common opinions about people with a mental illness and their families. RESULTS: People with higher level of self-esteem were less aware of stereotypes about patients and families. People with more severe psychopathology reported more awareness of stereotypes about families, not about patients. CONCLUSION: Enhancing psychological resources, by increasing self-esteem and the ability to cope with symptoms, can be targeted to diminish stereotype threat and improve stigma resilience. Interventions can be tailored to individual differences to increase their impact. Furthermore, in order to diminish detrimental consequences of negative stereotypes, mental health professionals, health educators and experts by experience can inform the public about mental illness and stigma.

For the purpose of diagnosis, psychopathology can be represented as categories of mental disorder, symptom dimensions or symptom networks. Also, psychopathology can be assessed at different levels of temporal resolution (monthly episodes, daily fluctuating symptoms, momentary fluctuating mental states). We tested the diagnostic value, in terms of prediction of treatment needs, of the combination of symptom networks and momentary assessment level.Fifty-seven patients with a psychotic disorder participated in an ESM study, capturing psychotic experiences, emotions and circumstances at 10 semi-random moments in the flow of daily life over a period of 6 days. Symptoms were assessed by interview with the Positive and Negative Syndrome Scale (PANSS); treatment needs were assessed using the Camberwell Assessment of Need (CAN).Psychotic symptoms assessed with the PANSS (Clinical Psychotic Symptoms) were strongly associated with psychotic experiences assessed with ESM (Momentary Psychotic Experiences). However, the degree to which Momentary Psychotic Experiences manifested as Clinical Psychotic Symptoms was determined by level of momentary negative affect (higher levels increasing probability of Momentary Psychotic Experiences manifesting as Clinical Psychotic Symptoms), momentary positive affect (higher levels decreasing probability of Clinical Psychotic Symptoms), greater persistence of Momentary Psychotic Experiences (persistence predicting increased probability of Clinical Psychotic Symptoms) and momentary environmental stress associated with events and activities (higher levels increasing probability of Clinical Psychotic Symptoms). Similarly, the degree to which momentary visual or auditory hallucinations manifested as Clinical Psychotic Symptoms was strongly contingent on the level of accompanying momentary paranoid delusional ideation. Momentary Psychotic Experiences were associated with CAN unmet treatment needs, over and above PANSS measures of psychopathology, similarly moderated by momentary interactions with emotions and context.The results suggest that psychopathology, represented as an interactome at the momentary level of temporal resolution, is informative in diagnosing clinical needs, over and above traditional symptom measures.

BackgroundPrevious research has suggested that the way bipolar patients respond to depressive mood impacts on the future course of the illness, with rumination prolonging depression and risk-taking possibly triggering hypomania. However, the relationship over time between variables such as mood, self-esteem, and response style to negative affect is complex and has not been directly examined in any previous study--an important limitation, which the present study seeks to address.MethodsIn order to maximize ecological validity, individuals diagnosed with bipolar disorder (N = 48) reported mood, self-esteem and response styles to depression, together with contextual information, up to 60 times over a period of six days, using experience sampling diaries. Entries were cued by quasi-random bleeps from digital watches. Longitudinal multilevel models were estimated, with mood and self-esteem as predictors of subsequent response styles. Similar models were then estimated with response styles as predictors of subsequent mood and self-esteem. Cross-sectional associations of daily-life correlates with symptoms were also examined.ResultsCross-sectionally, symptoms of depression as well as mania were significantly related to low mood and self-esteem, and their increased fluctuations. Longitudinally, low mood significantly predicted rumination, and engaging in rumination dampened mood at the subsequent time point. Furthermore, high positive mood (marginally) instigated high risk-taking, and in turn engaging in risk-taking resulted in increased positive mood. Adaptive coping (i.e. problem-solving and distraction) was found to be an effective coping style in improving mood and self-esteem.ConclusionsThis study is the first to directly test the relevance of response style theory, originally developed to explain unipolar depression, to understand symptom changes in bipolar disorder patients. The findings show that response styles significantly impact on subsequent mood but some of these effects are modulated by current mood state. Theoretical and clinical implications are discussed.