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Affective reactivity to daily stressors are increased in individuals in the early stages of psychosis. Studies in psychosis patients and healthy individuals at increased psychosis risk show altered neural reactivity to stress in limbic (i.e., hippocampus [HC] and amygdala), prelimbic (i.e., ventromedial prefrontal cortex [vmPFC] and ventral anterior cingulate cortex [vACC]), and salience areas (i.e., Anterior Insula [AI]). We investigated whether a similar pattern of neural reactivity is present in early psychosis individuals and if brain activity in these regions is associated with daily-life stress reactivity. Twenty-nine early psychosis individuals (11 at-risk mental state and 18 first-episode psychosis) completed the Montreal Imaging Stress Task in conjunction with functional MRI. The study was part of a large-scale randomized controlled trial on the efficacy of an acceptance and commitment therapy-based ecological momentary intervention for early psychosis. All participants also provided experience sampling methodology (ESM) data on momentary affect and stressful activities in their everyday environment. Multilevel regression models were used to estimate if daily-life stress reactivity was moderated by activity in (pre)limbic and salience areas. Task-induced stress was associated with increased activation of the right AI and decreased activation in the vmPFC, vACC, and HC. Task-induced changes in vmPFC and vACC activity were associated with affective stress reactivity, whereas changes in HC and amygdala activity were associated with higher overall stress ratings. These preliminary results suggest region-specific roles in affective and psychotic daily-life stress reactivity in early psychosis. The observed pattern suggests that chronic stress plays a role in neural stress reactivity.

Exposure to Stressful Life Events (SLEs) has been linked to psychosis. However, the combined effect of SLEs and familial risk on subclinical psychotic symptoms over time remains unknown. The objective of the present study was to investigate the effect of SLEs on the level of subclinical psychotic symptoms in individuals with and without familial vulnerability for psychosis. Data were collected from siblings of individuals diagnosed with psychotic disorder and healthy controls at baseline (N = 293) and three years later at follow-up (N = 928). We assessed self-reported and observer-rated subclinical positive, negative, and depressive psychotic symptoms. Participants reported the number of SLEs in the preceding 6 months. A multilevel multivariate regression analysis revealed a positive association between the retrospectively assessed number of SLEs and symptom levels, regardless of vulnerability status (p

Introduction/Objective: This study aimed to investigate efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual (TAU) for psychotic distress, in comparison to TAU. Methods: Individuals aged 15–65 years with clinically established ultra-high risk or first episode of psychosis were randomly assigned to TAU or ACT-DL+TAU. ACT-DL+TAU consisted of 8 ACT-sessions augmented with an EMI-app. The primary outcome was psychotic distress assessed with the Comprehensive Assessment scale of At Risk Mental State (CAARMS) at post-intervention and 6- and 12-month follow-up. Secondary outcomes were functioning, symptom severity, and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. Results: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomized to ACT-DL+TAU (n = 71) or TAU (n = 77). One hundred and fifteen (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of greater reduction in the primary outcome measure CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3) = 2.36; p = 0.50). However, out of the tested secondary outcomes, global functioning (χ2(3) = 9.05; p = 0.033), and negative symptoms (χ2(3) = 19.91; p2(3) = 21.56; p < 0.001). Conclusions: INTERACT did not support a significant effect of ACT-DL over TAU on the primary outcome measure of psychotic distress as assessed with the CAARMS. Although significant improvements were found for some secondary outcome measures, further replication studies are needed to confirm the strength and specificity of these effects.

Background Ambulatory monitoring is gaining popularity in mental and somatic health care to capture an individual's wellbeing or treatment course in daily-life. Experience sampling method collects subjective time-series data of patients' experiences, behavior, and context. At the same time, digital devices allow for less intrusive collection of more objective time-series data with higher sampling frequencies and for prolonged sampling periods. We refer to these data as parallel data. Combining these two data types holds the promise to revolutionize health care. However, existing ambulatory monitoring guidelines are too specific to each data type, and lack overall directions on how to effectively combine them. Methods Literature and expert opinions were integrated to formulate relevant guiding principles. Results Experience sampling and parallel data must be approached as one holistic time series right from the start, at the study design stage. The fluctuation pattern and volatility of the different variables of interest must be well understood to ensure that these data are compatible. Data have to be collected and operationalized in a manner that the minimal common denominator is able to answer the research question with regard to temporal and disease severity resolution. Furthermore, recommendations are provided for device selection, data management, and analysis. Open science practices are also highlighted throughout. Finally, we provide a practical checklist with the delineated considerations and an open-source example demonstrating how to apply it. Conclusions The provided considerations aim to structure and support researchers as they undertake the new challenges presented by this exciting multidisciplinary research field.

Introduction: Studies in daily life report that higher levels of positive affect (PA), but not negative affect (NA) are related to craving and alcohol consumption. However, these studies have mostly been performed in non-problematic drinkers. Therefore, this study compares how NA and PA are related to craving, non-heavy alcohol use, and binge drinking (BD) in patients with alcohol use disorder (AUD) and controls.Methods: A total of 53 female patients with AUD and 75 female controls were included in an experience sampling study where they reported on momentary NA, PA, craving, and alcohol use in daily life in a burst-measurement design over a period of 12 months. Assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of three weeks, all separated by 5-week periods of no assessment.Results: Subsequent craving was predicted by NA and PA in a quadratic fashion in patients with AUD, but not in controls. Future non-heavy alcohol use was predicted by lower levels of NA and higher levels of PA in patients with AUD and controls, but also by lower levels of PA in patients with AUD. Subsequent BD was predicted by PA in a quadratic manner in patients with AUD and controls, but also predicted by NA in a quadratic fashion in patients with AUD. Non-heavy alcohol use predicted subsequent lower levels of NA and PA, but this was not the case for BD.Conclusions: These results suggest that the relation between affect and craving or alcohol use is often non-linear in daily life. Furthermore, they show that a worse mood can indeed predict subsequent alcohol use in patients with AUD. However, this could be more pronounced for BD than for non-heavy alcohol use.

Purpose Chordomas are malignant tumors that develop along the neuraxis between skull-base and sacrum. Chondrosarcomas show similarities with chordomas, yet show less malignant behavior. LIM and SH3 protein 1 (LASP1) is a cytoskeletal protein known to promote the malignant behavior of tumors. LASP1 was previously identified as a possibly overexpressed protein in a chordoma proteomics experiment. In this study we compare LASP1 expression in chordoma and chondrosarcoma tissue. Methods Biopsies of primary tumors were collected from surgically treated chordoma (n = 6) and chondrosarcoma (n = 6) patients, flash-frozen upon collection and collectively analyzed for LASP1 RNA (real-time PCR) and protein expression (western blotting). Additionally, tissue micro array (TMA)-based immunohistochemistry was applied to an archive of 31 chordoma and 1 chondrosarcoma specimen. Results In chordoma samples, LASP1 mRNA was detected in 4/6 cases and a strong 36 kDa immunoreactive protein band was observed in 4/5 cases. In contrast, 0/6 chondrosarcoma samples showed detectable levels of LASP1 mRNA and only a weak 36 kDa band was observed in 4/5 cases. Immunohistochemical analysis showed LASP1 expression in all chordoma samples, whereas chondrosarcoma specimen did not show immunoreactivity. Conclusion LASP1 is strongly expressed in the majority of chordoma cases and shows low expression in chondrosarcoma tissue. Since LASP1 is known to function as oncogene and regulate cell proliferation in other tumor types, this study implicates a role for LASP1 in chordoma biology. Further studies are warranted to improve understanding of LASP1’s expression and functioning within chordoma, both in vitro and in vivo.

Key symptoms of anxiety include experiencing unpleasant emotions and hyperarousal. Growing evidence suggests the role of delayed affective recovery from stress (DAR) in their maintenance and development on a day-to-day basis. We aimed to investigate whether DAR is linked to current and future anxiety symptoms, independently of depressive symptoms. Self-reported anxiety and depressive symptoms were assessed twice: at Wave 1 (N=1031) and approximately 2.5 years later at Wave 2 (N=171) in a community sample of adolescents. Additionally, at Wave 1, Experience Sampling Method (ESM) was used. Participants reported their momentary affect and stressful occurrences 10 times a day, for six days. Using ESM data and a subtraction method, we construed two variables, i.e., affective valence and arousal reflecting the (un)pleasantness and (hyper)arousal associated with emotions. The time interval for affective recovery was estimated using parametric survival analysis. Prospective associations were tested with multiple regression. Slower valence recovery was associated with higher concurrent anxiety symptoms (p

BACKGROUND As mobile health (mHealth) studies become increasingly productive due 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. OBJECTIVE We examine the factors that affect participants’ responsiveness to ecological momentary assessments (EMA) in a 10-day wearable and EMA-based affect sensing mHealth study. We study the physiological relationships indicative of receptivity and affect while also analyzing the interaction between the two constructs. METHODS We collected the data from 45 healthy participants wearing two devices measuring electrodermal activity, acceleration, electrocardiography, and skin temperature while answering 10 EMAs a day containing questions related to perceived mood. Due to the nature of our constructs, we can only obtain ground truth measures for both affect and receptivity during a response. Therefore, we utilized unsupervised and supervised learning methods to infer affect when a participant did not respond. Our unsupervised method used k-means clustering to find the relationship between physiological relationships and responsiveness then inferred the emotional state during non-responses. For the supervised learning method, we primarily used Random Forest (RF) and Neural Networks (NN) to predict affect of unlabeled data points. RESULTS Based on our findings we showed that using a receptivity model to trigger EMAs will decrease the reported negative affect by more than 3 points or 0.29 standard deviation using our psychological instrument scored between 13 and 91. The findings also showed a bimodal distribution of our predicted affect during non-responses. CONCLUSIONS Our results showed a clear relationship between affect and receptivity. This relationship can affect the efficacy of a mHealth study, particularly those studies that employ a learning algorithm to trigger EMAs. Therefore, we propose a smart trigger that promotes EMA and JITI receptivity without influencing affect during sampled time points as future work.

Purpose A chordoma is a slow-growing, invasive neoplasm in the neuraxis, thought to arise from notochordal cells. At 10-year follow-up, the average survival rate is 50%, though the interindividual prognosis varies substantially. Here, we aim to provide a comprehensive overview of the genes and proteins expressed in these tumors and their prognostic value, as to facilitate prognostication for chordoma patients. Methods A systematic search of clinical studies that investigated expressed factors related to chordoma survival was performed in PubMed. Data extraction included RNA and protein expression data and prognostic value (in terms of overall survival, progression free survival, disease free survival and recurrence free survival), both by univariate and multivariate analysis. Results Seventy-eight original studies, collectively evaluating 134 expressed factors, were included in this review. By univariate analysis 96, and by multivariate analysis 32 of these molecular factors had a predictive value for patient survival. Of those studied in multivariate analyses, 26 factors had a negative effect while six had a positive effect on patient survival. Conclusions Identification of molecular factors that are associated with survival contributes towards better prognostication of chordoma patients. Given chordoma’s rarity, oftentimes only univariate analyses can be performed. Robust multivariate analyses are scarcer but provide independently significant prognostic factors. The data presented in this review aids in prognostication for the individual patient and facilitates the development of targeted therapies.

Background: Individuals with chronic psychosis consistently show impairment in emotion regulation (ER). However, little is known about how contextual appraisals shape ER strategy use in individuals in the early stages of psychosis. The present study investigates the extent to which different appraisal dimensions of the most negative and positive events of the day are associated with ER strategy use in individuals with ultra-high risk (UHR) and first-episode psychosis (FEP).Method: Sixty-eight UHR individuals and fifty-five FEP individuals filled out an experience sampling evening questionnaire for six consecutive days, in which their appraisal of intensity, importance and perceived control concerning the most negative or positive event of the day, and the ER strategies they deploy in response to these events were measured.Results: Multilevel mixed effect models showed that intensity appraisal was most closely associated with ER strategy use, as opposed to importance and controllability appraisals. Higher intense negative events were associated with more rumination and social sharing, while less intense negative events were associated with more reappraisal. Higher intense positive events were associated with a greater number of deployed strategies and more efforts in using savoring, expression and social sharing. The UHR and FEP individuals did not significantly differ regarding effects of above-mentioned appraisal dimensions on ER.Conclusions: These results provide evidence supporting ER flexibility in early psychosis, and event intensity emerged as the dimension most strongly associated with ER. Future research should better account for other situational factors (such as social context) that might affect ER use in psychosis.

Typical measures of laboratory reactivity (i.e. difference between control and stress) and recovery (i.e. difference between stress and post-stress) were compared with a conventional measure of daily-life reactivity, best known as event-related stress. Fifty-three healthy individuals between 19 and 35 years of age took part in a laboratory session where stress was induced using the repeated Montreal Imaging Stress Task and 8 days of experience sampling method. Measures of negative affect, heart rate (HR), HR variability, and skin conductance level were collected. Findings show no strong associations between laboratory and daily life measures with the exception of laboratory affective recovery and daily life reactivity. Findings and their implications are discussed.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the International Classification of Diseases (ICD-11) proposed a dimensional approach to the assessment of personality disorders (PDs). Both models dictate that the clinician first determines PD severity before assessing maladaptive traits, invoking the level of personality functioning (LPF) construct. We consider LPF a promising dimensional construct for translational research because of its clinical importance and conceptual overlap with the Research Domain Criteria (RDoC) Social Processes. We aim to identify biomarkers that co-vary with fluctuations in LPF in adulthood, ultimately to predict persistent decrease in LPF, associated with suicidality and morbidity. However, a theoretical framework to investigate stress-related oscillations in LPF is currently missing. In this article, we aim to fill this hiatus with a critical review about stress and LPF. First, we discuss acute stress and LPF. We briefly present the basics of the neurophysiological stress response and review the literature on momentary and daily fluctuations in LPF, both at a subjective and physiological level. Second, we review the effects of chronic stress on brain function and social behaviour and recapitulate the main findings from prospective cohort studies. This review underlies our suggestions for multimethod assessment of stress-related oscillations in LPF and our theoretical framework for future longitudinal studies, in particular studies using the experience sampling method (ESM). ispartof: CLINICAL PSYCHOLOGY & PSYCHOTHERAPY vol:28 issue:5 pages:1181-1193 ispartof: location:England status: published

OBJECTIVE: The aim of this study is to investigate the time to affective recovery from daily-life stressors between healthy controls (HC) and two groups with an increased risk for developing depression: individuals with subclinical symptoms of depression (SSD), and individuals remitted from a depressive episode with residual symptoms of depression (RRS). METHOD: The experience sampling method (ESM) was used to measure affective recovery to daily-life stressors. Affective recovery was defined as the moment that negative affect (NA) returned to baseline level following the first stressful event of the day. We assessed two different operationalizations of the baseline: NA at the moment before the stressful event (t-1), and mean-person NA. The effect of stress intensity, and cumulative stress were also assessed. RESULTS: Survival analyses showed significantly longer recovery times for the at risk groups in comparison to healthy individuals, albeit no significant difference was found between the two at risk groups (i.e. SSD and RRS). There was also an effect of cumulative stress, but not stress intensity on time to recovery in that cumulative stress resulted in significantly longer recovery times for all three groups. LIMITATIONS: The present study is limited by the ESM sampling design, assessments take place post-stress and therefore do not capture peak stress. Additionally, we are only able to assess patterns at the group level. Finally, there is a significant age difference between groups. CONCLUSION: Individuals at risk for depression display a delayed recovery to daily-life stressors when compared to healthy controls, which is not explained by differences in stress intensity or cumulative stress. Understanding what is driving this delay may help combat the development of depression. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:320 pages:499-506 ispartof: location:Netherlands status: published

BACKGROUND Identifying 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 (i.e., a longer duration until affect reaches baseline levels after stress), but evidence on positive affective recovery as a putative protective mechanism remains limited. OBJECTIVE This study aimed to investigate trajectories of positive affect in response to stress across the continuum of mental disorder in a transdiagnostic sample. METHODS Using 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 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. RESULTS Baseline 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. CONCLUSIONS The results provide first evidence that positive affective recovery may be relevant within transdiagnostic subclinical and clinical stages of mental disorder suggesting it may be a potential target for mobile health interventions fostering resilience in daily life.

BackgroundWe investigated treatment effects of Acceptance and Commitment Therapy in Daily Life (ACT-DL) on psychological flexibility (PF) and the moderating role of the therapeutic working alliance on these effects in patients with early psychosis.MethodsACT-DL is an ecological momentary intervention (EMI) combining face-to-face ACT with a smartphone app. In the multi-center INTERACT randomized controlled trial, n=148 early psychosis individuals were randomized to either treatment as usual (TAU as the control condition, n=77) or to ACT-DL in addition to TAU (ACT-DL + TAU as the experimental condition, n=71). We assessed global PF and the therapeutic alliance with self-report questionnaires. In addition, we used the experience sampling methodology (ESM) to assess PF with a momentary (in-the-moment and since-the-previous-beep openness) and an evening (daily PF) questionnaire. Assessments took place at baseline, post-intervention (POST), six (FU6), and twelve months (FU12) follow-up.ResultsGlobal (B=19.49 to 33.14; all P-valuesConclusionOur results provide partial support for the capability of ACT-DL to improve daily life measures of openness, and emphasize the importance of the therapeutic relationship in supporting processes of change.

The experience sampling method (ESM) has revolutionized our ability to conduct psychological research in the natural environment. However, researchers have a large degree of freedom when preprocessing ESM data, which may hinder scientific progress. This study illustrates the use of multiverse analyses regarding preprocessing choices related to data exclusion (i.e., based on various levels of compliance and exclusion of the first assessment day) and the calculation of constructs (i.e., composite scores calculated as the mean, median, or mode) by reanalyzing established group differences in negative affect, stress reactivity, and emotional inertia between individuals with and without psychosis. Data came from five studies and included 233 individuals with psychosis and 223 healthy individuals (in total, 26,892 longitudinal assessments). Preprocessing choices related to data exclusion did not affect conclusions. For both stress reactivity and emotional inertia of negative affect, group differences were affected when negative affect was calculated as the mean compared to the median or mode. Further analyses revealed that this could be attributed to considerable differences in the within- and between-factor structure of negative affect. While these findings show that observed differences in affective processes between individuals with and without psychosis are robust to preprocessing choices related to data exclusion, we found disagreement in conclusions between different central tendency measures. Safeguarding the validity of future experience sampling research, scholars are advised to use multiverse analysis to evaluate the robustness of their conclusions across different preprocessing scenarios. ispartof: Behavior Research Methods vol:54 issue:6 pages:2981-2992 ispartof: location:United States status: published

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.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.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.Netherlands Trial Register, ID: NTR4252. Registered on 26 September 2013.

Multimodal wearable physiological data in daily life have been used to estimate self-reported stress labels. However, missing data modalities in data collection makes it challenging to leverage all the collected samples. Besides, heterogeneous sensor data and labels among individuals add challenges in building robust stress detection models. In this paper, we proposed a modality fusion network (MFN) to train models and infer self-reported binary stress labels under both complete and incomplete modality conditions. In addition, we applied personalized attention (PA) strategy to leverage personalized representation along with the generalized one-size-fits-all model. We evaluated our methods on a multimodal wearable sensor dataset (N=41) including galvanic skin response (GSR) and electrocardiogram (ECG). Compared to the baseline method using the samples with complete modalities, the performance of the MFN improved by 1.6% in f1-scores. On the other hand, the proposed PA strategy showed a 2.3% higher stress detection f1-score and approximately up to 70% reduction in personalized model parameter size (9.1 MB) compared to the previous state-of-the-art transfer learning strategy (29.3 MB)., 2021 9th International Conference on Affective Computing and Intelligent Interaction (ACII)

BACKGROUND Acceptance and Commitment Therapy (ACT) is promising in the treatment of early psychosis. Augmenting face-to-face ACT with a mobile health (mHealth) ecological momentary intervention (EMI) may increase its treatment effects and empower clients to take treatment into their own hands. OBJECTIVE This study aimed to investigate treatment adherence to and acceptability of Acceptance and Commitment Therapy in Daily Life (ACT-DL), a novel Ecological Momentary Intervention for people with Ultra-High-Risk (UHR) state and a First-Episode Psychosis (FEP). METHODS In the multi-center INTERACT randomized controlled trial, UHR and FEP individuals aged 15-65 were randomized to treatment as usual only (TAU) (control) or to ACT-DL+TAU (experimental), consisting of 8 face-to-face sessions augmented with an ACT-based smartphone application, delivering ACT skills and techniques in daily life. We collected data on treatment adherence to and acceptability of ACT-DL. Predictors included baseline demographic, clinical and functional outcomes. RESULTS ACT-DL+TAU participants (n=71) completed a mean of 6 (SD=3) sessions, with 59% (n=42) of participants completing all sessions. App adherence data (n=58) shows that, on a weekly basis, participants used the app 13 times and were compliant to 6 out 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% reported perceived burden by number and length of notifications (scores ≥2; 1=no burden). Ethnic minority background predicted lower notification response compliance (b=-4.37; p=.012), yet higher app usefulness (b=1.25; p=.049). Negative (b=-0.26; p=.010) and affective (b=0.14; p=.04) symptom severity predicted lower and higher ACT training usefulness respectively. Being female (b=-1.03; p=.049) predicted lower usefulness of the ACT metaphor images on the app. CONCLUSIONS Our results corroborate good treatment adherence to and acceptability of ACT-DL in early psychosis. We provide recommendations for future intervention optimization. CLINICALTRIAL The trial was prospectively registered within the Dutch Trial Register (ID: NTR4252). INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-019-3912-4

ImportanceTreatment in the early stages of psychosis is crucial to prevent poor clinical and social outcomes. Currently, no preventive interventions are available that reduce psychotic distress, or affective and negative symptoms as well as functioning, calling for more and dedicated treatments for these.ObjectiveTo investigate the efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual for psychotic distress, in comparison to treatment as usual only.DesignThis single-blinded randomized clinical INTERACT trial investigated participants post-intervention and at 6 and 12-month follow-up. Participants were recruited between June 1, 2015 and December 31, 2018. Assessors were blinded to treatment allocation.SettingINTERACT is a multi-center trial recruiting participants from secondary mental health services in 5 regions in Belgium and The Netherlands.ParticipantsThe sample was a referral sample of individuals aged 15-65 years with a clinically established UHR or FEP status.InterventionsIndividuals were randomly assigned (1:1) to ACT-DL, consisting of 8 ACT sessions augmented with an EMI app in addition to treatment as usual, or to treatment as usual only.Main outcomes and measuresThe primary outcome was a reduction in psychotic distress as assessed with CAARMS at post-intervention, 6-and 12-month follow-up. Secondary outcomes included symptom severity (measured with BPRS and BNNS), functioning (measured with SOFAS and SFS) and momentary psychotic distress (measured with the Experience Sampling Method, a structured diary technique). All analyses were described in the trial protocol and in a postregistration on the open-science framework, prior to accessing the data.ResultsOf the 196 individuals assessed for eligibility, 148 were randomized to ACT-DL+TAU (n=71) or TAU (n=77) (72 female (49%), average age 25 (SD = 6), 71 FEP (48%)). 115 (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of a greater reduction in CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3)=2.38; p=.50). However, general psychopathology (χ2(3)=14.44; p=.002); affective (χ2(3)=8.55; p=.04) and negative symptom severity (χ2(3)=19.96; p2(3)=15.96; p=.001) in. Furthermore, global functioning improved (χ2(3)=8.72; p=.033) in ACT-DL+TAU compared to TAU, whereas social functioning failed to reach significance (χ2(3)=7.41; p=.060). Finally, a clear and significant reduction was found in momentary psychotic distress (χ2(3)=21.56; p2(3)=1.02; p=.599), momentary positive (χ2(3)=4.17; p=.124) or negative (χ2(3)=2.78; p=.249) affect. No serious adverse events directly related to the therapy occurred.Conclusions and relevanceINTERACT did not support a significant effect on psychotic distress as assessed with the CAARMS. However, significant improvements were found for momentary psychotic distress, global functioning and negative symptomatology. These results are promising given that these latter problems are among the hardest to treat.Trial RegistrationDutch Trial Register: NTR4252Key PointsQuestionCan Acceptance and Commitment Therapy (ACT) in Daily Life, a combined face-to-face ACT intervention with a digital daily life Ecological Momentary Intervention, reduce psychotic distress in the early stages of psychosis?FindingsThis randomized clinical trial of 148 individuals in the early stages of psychosis (UHR or FEP) found no evidence that ACT-DL improved psychotic distress at post-intervention, 6 or 12-month follow-up over and above treatment as usual. However, significant effects were found for momentary psychotic distress, negative symptoms and functioning.MeaningWhereas the blended care approach of face-to-face ACT with the ACT-DL EMI did not improve psychotic distress over and above treatment as usual, it provided a promising avenue for the treatment of momentary psychotic distress as well as for negative symptoms and improving functioning, some of the hardest to treat problems in individuals with UHR and FEP.

BackgroundOne putative psychological mechanism through which momentary stress impacts on psychosis in individuals with increased liability to the disorder is via affective disturbance. However, to date, this has not been systematically tested. We aimed to investigate whether (i) cross-sectional and temporal effects of momentary stress on psychotic experiences via affective disturbance, and (ii) the reverse pathway of psychotic experiences on stress via affective disturbance were modified by familial liability to psychosis.MethodsThe Experience Sampling Method was used in a pooled data set of six studies with three groups of 245 individuals with psychotic disorder, 165 unaffected first-degree relatives, and 244 healthy control individuals to index familial liability. Multilevel moderated mediation models were fitted to investigate indirect effects across groups cross-sectionally and multilevel cross-lagged panel models to investigate temporal effects in the proposed pathways across two measurement occasions.ResultsEvidence on indirect effects from cross-sectional models indicated that, in all three groups, effects of stress on psychotic experiences were mediated by negative affect and, vice versa, effects of psychotic experiences on stress were mediated by negative affect, with all indirect effects being weakest in relatives. Longitudinal modelling of data provided no evidence of temporal priority of stress in exerting its indirect effects on psychotic experiences via affective disturbance or, vice versa.ConclusionsOur findings tentatively suggest a rapid vicious cycle of stress impacting psychotic experiences via affective disturbances, which does, however, not seem to be consistently modified by familial liability to psychosis.

Background: Treatment in the early stages of psychosis is crucial to prevent poor clinical and social outcomes. The aim of this study was to investigate the efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in reducing psychotic distress in a multi-centre randomised controlled trial of individuals with an Ultra-high Risk for Psychosis (UHR) or a first-episode of psychosis (FEP). Methods: Individuals aged 15-65 years with a clinically established UHR or FEP status were recruited from secondary mental health services in 5 regions and were randomly assigned to treatment as usual (TAU) or ACT-DL+TAU. ACT-DL consisted of 8 ACT sessions augmented with an EMI app. The primary outcome was a reduction in psychotic distress as assessed with CAARMS at post-intervention, 6- and 12-month follow-up. Secondary outcomes were symptom severity, functioning and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. Findings: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomised to ACT-DL+TAU (n=71) or TAU (n=77). 115 (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of a greater reduction in CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3)=2·38; p=0·50). However, momentary psychotic distress (χ2(3)=21·56; p

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.

BACKGROUND: A psychosocial task that can induce comparable levels of stress repeatedly is fundamental to effectively study changes in stress reactivity over time or as a result of an intervention. However, existing tasks have struggled to provide consistent stress responses across repeated trials. AIM: The goal was to assess the efficacy of two different designs of the repeated Montreal Imaging Stress Test (rMIST) in reproducing the same pattern of reactivity over two separate sessions. METHODS: In two different studies, stress was induced using the rMIST on two separate sessions, one week apart. Each study used a different task design. In the first study (53 participants [45 women]; mean age=24.16 [SD=3.29]), the rMIST consisted of a single-longer stress exposure, while the second study (30 participants [27 women]; mean age=21.81 [SD=2.09]) consisted of several shorter stress exposures per session. Self-reported (i.e perceived stress [PS] and negative affect [NA]), physiological (i.e heart rate [HR], root mean square of successive differences [RMSSD]) and hormonal (i.e. salivary cortisol) measures of stress were used. RESULTS: Stress reactivity was comparable across the two repeated stress sessions in both studies. However, baseline HR in the second session increased relative to the first session in the first study, and there was no cortisol response. Additionally, there was a decrease in HR and HRV reactivity within the session on the second study, suggesting a habituation effect not between but within the session itself. CONCLUSION: The rMIST overcomes some of the challenges associated with repeated stress induction. However, an anticipation effect and a lack of cortisol response indicate that further adjustments to the task are necessary. Finally, task design is important for repeated stress reactivity. ispartof: PSYCHONEUROENDOCRINOLOGY vol:128 ispartof: location:England status: published

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.

IntroductionPreliminary results indicate that COVID-19 lockdown measures could lead to an increase in eating disorder pathology. However, some patients could be more vulnerable to experience such an increase than others. The reason why some patients are more susceptible to the impact of lockdown measures is still not known.ObjectivesTo analyze the impact of the Belgian COVID-19 lockdown measures on the surroundings, social context, negative affect (NA), positive affect (PA) and binge eating frequency of patients with bulimia nervosa (BN).Methods The data of 15 female patients with BN from an ongoing experience sampling method study were analyzed. Mixed effects models compared surroundings, social context, NA, PA and binge eating before and after the implementation of the lockdown measures.Results After the implementation of the lockdown measures, significant changes in surroundings and social context were found as well as an increase in NA (p < 0.001) and decrease in PA (p = 0.015). Patients who experienced an increase in binge eating frequency also experienced a stronger increase in NA (p = 0.012) and decrease in PA (p = 0.026) after the lockdown measures were implemented.ConclusionsFuture research should also look at changes in surroundings, social context, affect and how these interact with factors such as personality traits and coping styles when investigating why some patients are more susceptible to the negative effects of lockdown measures than others.

In this study, the feasibility and efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), ACT augmented with a daily life application, was investigated in 55 emerging adults (age 16 to 25) with subthreshold depressive and/or psychotic complaints. Participants were randomized to ACT-DL (n = 27) or to active control (n = 28), with assessments completed at pre- and post-measurement and 6- and 12-months follow-up. It took up to five (ACT-DL) and 11 (control) months to start group-based interventions. Participants attended on average 4.32 out of 5 ACT-DL sessions. On the app, they filled in on average 69 (48%) of signal-contingent beep-questionnaires, agreed to 15 (41%) of offered beep-exercises, initiated 19 on-demand exercises, and rated ACT-DL metaphors moderately useful. Relative to active control, interviewer-rated depression scores decreased significantly in ACT-DL participants (p = .027). Decreases in self-reported depression, psychotic-related distress, anxiety, and general psychopathology did not differ between conditions. ACT-DL participants reported increased mean NA (p = .011), relative to active controls. Mean PA did not change in either group, nor did psychological flexibility. ACT-DL is a feasible intervention, although adaptations in future research may improve delivery of and compliance with the intervention. There were mixed findings for its efficacy in reducing subthreshold psychopathology in emerging adults. Dutch Trial Register no.: NTR3808. ispartof: BEHAVIOUR RESEARCH AND THERAPY vol:128 ispartof: location:England status: published

Objective Results from experimental studies suggest that psychosis and psychosis liability are associated with increased cortisol levels and blunted cortisol reactivity, and that use of antipsychotics may reduce these aberrations. Here, we report on overall cortisol, diurnal slope, and cortisol stress reactivity in everyday life in psychosis and psychosis liability using the experience sampling method (ESM). Methods Our sample consisted of individuals diagnosed with psychotic disorder currently on (MPD; n = 53) or off antipsychotic medication (NMPD; n = 20), first-degree relatives of psychotic patients (REL; n = 47), and healthy volunteers (HV; n = 67). Saliva samples were collected throughout the day on six consecutive days and analyzed for cortisol levels. Simultaneously, stressfulness of the current activity was assessed with ESM questionnaires. Results We found no group differences in overall cortisol level between groups, but REL had a steeper diurnal slope than HV; in MPD a trend was found in the same direction. Regarding reactivity to stressful activities, results indicated attenuation of the cortisol response in both patient groups compared to HV. Conclusion These results do not confirm reports of increased cortisol levels in psychosis, but provide evidence of stress-related cortisol alterations in everyday life.

BackgroundAbnormalities in reward learning in psychotic disorders have been proposed to be linked to dysregulated subcortical dopaminergic (DA) neurotransmission, which in turn is a suspected mechanism for predisposition to psychosis. We therefore explored the striatal dopaminergic modulation of reward processing and its behavioral correlates in individuals at familial risk for psychosis.MethodsWe performed a DA D2/3 receptor [18F]fallypride positron emission tomography scan during a probabilistic reinforcement learning task in 16 healthy first-degree relatives of patients with psychosis and 16 healthy volunteers, followed by a 6-day ecological momentary assessment study capturing reward-oriented behavior in the everyday life.ResultsWe detected significant reward-induced DA release in bilateral caudate, putamen and ventral striatum of both groups, with no group differences in its magnitude nor spatial extent. In both groups alike, greater extent of reward-induced DA release in all regions of interest was associated with better performance in the task, as well as in greater tendency to be engaged in reward-oriented behavior in the daily life.ConclusionsThese findings suggest intact striatal dopaminergic modulation of reinforcement learning and reward-oriented behavior in individuals with familial predisposition to psychosis. Furthermore, this study points towards a key link between striatal reward-related DA release and pursuit of ecologically relevant rewards.

Purpose: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology.Methods: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model.Results: Linear analyses showed that emotional stress reactivity was not associated with onset (β = .02; P = .56) or persistence (β = −.01; P = .78) of symptoms. There was a significant effect of baseline symptom score (β = .53; P β = .19; P β = .25; P β = −.03; P = .65) or severe (β = −.06; P = .42), stressors was associated with symptom persistence one year later.Discussion: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

Background Repeated exposure to stressors can sensitize the stress system and in turn propel the development of various psychiatric disorders. Stress sensitization can be identified through stress reactivity patterns. Individuals at risk of developing psychosis for example, already show aberrant patterns of daily stress reactivity prior to clinical diagnosis, with blunted physiological responses to mild stressors that could be indicative of a dysregulation of the hypothalamic pituitary adrenocortical axis. In parallel, while they do not show significant physiological responses to the stressor, they report significant increases in negative affect (NA) ensuing from it. This study aims to test whether sensitization can already be observed in healthy volunteers exhibiting only subclinical symptoms. Methods Thirty, first year students took part in two laboratory sessions where stress was induced using a modified version of the Montreal Imaging Stress Task (MIST), one week apart. Baseline measures of psychopathology were collected using the Symptom Checklist 90 (SCL-90). During the laboratory sessions, continuous ECG signals were collected, as well as five subjective stress measures per session. We calculated average heart rate (HR) and heart rate variability (HRV) per condition. Multilevel models testing the three-way interaction between psychopathology, session, and condition with individual data points nested within days were used to assess overall psychopathology and more specifically subclinical symptoms of psychosis in repeated stress reactivity. Results Mixed models investigating repeated stress in overall psychopathology indicates a significant three way interaction for HR (β = -.15, SE=.01, p< .01), and HRV (β = -.01, SE=.04, p= .02), with individuals scoring lower on the scl-90 exhibiting comparable increases in HR and decreases in HRV on both sessions. In contrast, individuals scoring higher on the scale show a blunted response on the second session compared to the first. Analyses with stress (β = .03, SE= .01, p= .01), and NA (β = .06, SE=.29, p= .03) show that generally the stressor elicited a mild negative subjective response with a decrease in stress and NA that was comparable on both sessions for individuals scoring lower on the scl-90. No subjective reactivity was reported on the second session for participants scoring high on the scale. Likewise, models that focused on subclinical psychotic symptoms found similar significant interactions. In the same way as in the analyses with psychopathology we find significant interactions for stress (β = .36, SE= .11, p< .01), NA (β = .06, SE=.03, p= .03) HR (β = -1.08, SE=.13 p< .01), and HRV (β = 3.72, SE=.39, p< .01). Analyses show the same comparable patterns of reactivity in both sessions for participants low in psychosis, and a blunted response on the second session for participants high in psychosis. Discussion Symptoms of psychopathology and more specifically psychosis are related to blunted stress reactivity during a second exposure to the same stressor. Psychopathological vulnerability may be reflected in a blunting response to repeated stress in healthy individuals with subclinical symptoms. Findings suggest that dysregulation in the stress system may be present long before individual complaints, further highlighting the need for early intervention.

Background Acceptance and Commitment Therapy (ACT) is a third-wave cognitive-behavioral intervention that holds promise for treatment of individuals in the early stages of psychosis. To increase its treatment effects, we have developed an ACT smartphone app that can be used as an add-on to traditional ACT – ACT in Daily-Life (ACT-DL). Augmenting face-to-face ACT with a mobile health ecological momentary intervention (EMI) may empower clients to take treatment into their own hands and bridge the treatment-practice gap. We tested the feasibility and acceptability of ACT-DL as part of a randomized controlled trial in individuals in the early stages of psychosis. Methods Participants at ultra-high risk (UHR) for, or with a first episode of psychosis (FEP) were randomized to ACT-DL (n=71) or to treatment-as-usual (n=77). In ACT-DL, participants followed seven face-to-face individual ACT-sessions. After each session, they took home a smartphone with the ACT-DL app installed on it that reminded individuals of ACT principles with visual cues of metaphors and provided exercises, 8 times a day for three subsequent days. On-demand exercises were always available. We gathered user data on adherence to app notifications, on-demand use of the app, and rated metaphor usefulness after each session. At post-measurement, a debriefing questionnaire assessed user evaluation on the use, usefulness, and burden of (parts of) the ACT-DL intervention. Results ACT-DL participants attended on average 5 out of 7 ACT sessions, with 42 completing all sessions. App user data (n=58) showed that on a weekly basis, participants interacted on average 16 times with the ACT-DL app, responding to 25% of the notifications, and initiating 5 on-demand exercises. Perceived usefulness of ACT-metaphors varied substantially between participants and weeks. Neither clinical status (UHR vs FEP), nor other baseline (or therapy) related variables were related to dropout, while minority status (b=-4.88; p Discussion This study showed that, despite large between-subject variability, early psychosis patients are largely positive about ACT-DL, acknowledging the usefulness of the app to implement ACT in their daily lives, the homework exercises, and the face-to-face sessions. This argues for the use of a blended care approach in early psychosis. However, the relatively low number of completion rates and app compliance, the perceived burden from notifications, and the variability in perceived usefulness of (parts of) the app, corroborates the need for future improvements in intervention design. I will provide suggestions for app optimisation.