The efficacy of combining cognitive training and noninvasive brain stimulation: A transdiagnostic systematic review and meta-analysis.

Over the past decade, an increasing number of studies investigated the innovative approach of supplementing cognitive training (CT) with noninvasive brain stimulation (NIBS) to increase the effects on outcomes. In this review, we aim to summarize the evidence for this treatment combination. We identified 72 published and unpublished studies (reporting 773 effect sizes), including 2,518 participants from healthy and clinical populations indexed in PubMed, MEDLINE, APA PsycInfo, ProQuest, Web of Science, and https://ClinicalTrials.gov (last search: August 9, 2022) that compared the effects of NIBS combined with CT on cognitive, symptoms, and everyday functioning to CT alone at postintervention and/or follow-up. We performed random-effects meta-analyses with robust variance estimation and assessed risk of bias with the Cochrane ROB tool. Only four studies had low risk of bias in all domains, and many studies lacked standard controls such as keeping the outcome assessor and trainer unaware of the treatment condition. Following sensitivity analyses, only learning/memory robustly improved significantly more when CT was combined with NIBS compared to CT only (g = 0.18, 95% CI [0.07, 0.29]) at postintervention, but not in the long term. The effect was small and limited by substantial heterogeneity. The other seven cognitive outcome domains, symptoms, and everyday functioning did not benefit from adding NIBS to CT. Given the methodological limitation of prior studies, more high-quality trials that focus on the potential of combining NIBS and CT to enhance benefits in everyday functioning in the short and long term are needed to evaluate whether combining NIBS and CT is relevant for clinical practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sleep disorders in a naturalistic cohort of Dutch psychiatric outpatients: prevalence rates and associations with psychopathology symptom severity and well-being.

Sleep problems are very common in individuals with a mental disorder. Given the abundant evidence indicating the negative impact of disturbed sleep on mental health outcome, insight into the prevalence of all types of sleep disorders in specific mental disorders and neurodevelopmental conditions is of practical importance. Therefore, we estimated the prevalence of six types of sleep disorders with the Holland Sleep Disorders Questionnaire in an overall mental health sample (n = 1082) and separately for different mental and neurodevelopmental conditions. Furthermore, associations between specific sleep disorders, psychopathology and well-being were studied. The impact of the total number of sleep disorders on these associations was examined. Overall, 46.2% of all participants scored above the cut-off for having a sleep disorder. Specifically, 26.8% scored on insomnia, 12.1% on sleep breathing disorders, 9.7% on hypersomnia, 13.7% on circadian rhythm sleep-wake disorders, 11.2% on parasomnia, and 17.9% on sleep-related movement disorders. Most sleep disorders were associated with greater severity of psychopathology and lower well-being. These associations got stronger with an increasing number of sleep disorders. Our study revealed higher suspected prevalence of most sleep disorders in a mental disorder sample compared to the general population. Moreover, the presence of sleep disorder(s) was strongly associated with symptom severity and reduced well-being. These findings extend the notion that early detection and treatment of sleep disorders in mental health populations is essential for psychiatric outcome.

A single-session VR intervention addressing self-compassion and self-criticism with and without perspective change: Results of a randomized controlled experiment.

Excessive self-criticism is an important transdiagnostic psychological factor. In contrast, self-compassion can contribute to the resilience and recovery of clinical populations, making this an important target for treatment. Virtual Reality (VR) has the potential to improve existing interventions as it allows for personalized roleplays that can be experienced from different perspectives, by using the novel VR technique of perspective change. We investigated the effects of a VR intervention on self-criticism and self-compassion, and the added value of changing perspectives. In total, 68 undergraduate students with high levels of self-criticism were randomized to either the perspective change condition or the control condition. Participants played two roleplays in which they had to react compassionately toward a virtual character that expressed the participants' own self-critical thoughts. In the perspective change condition, after each roleplay perspective change was used to receive one's own compassionate words. Results showed that self-compassion increased and self-criticism decreased significantly in both conditions. No significant differences were found for negative and positive affect. Furthermore, no differences were found between the conditions. Thus, receiving compassionate words through perspective change had no additional effect. Expressing compassion to someone with similar self-criticism showed to be sufficient to reduce self-criticism and increase self-compassion.

Cognitive Underperformance in a Mixed Neuropsychiatric Sample at Diagnostic Evaluation of Adult ADHD.

(1) Background: The clinical assessment of attention-deficit/hyperactivity disorder (ADHD) in adulthood is known to show non-trivial base rates of noncredible performance and requires thorough validity assessment. (2) Objectives: The present study estimated base rates of noncredible performance in clinical evaluations of adult ADHD on one or more of 17 embedded validity indicators (EVIs). This study further examines the effect of the order of test administration on EVI failure rates, the association between cognitive underperformance and symptom overreporting, and the prediction of cognitive underperformance by clinical information. (3) Methods: A mixed neuropsychiatric sample (N = 464, ADHD = 227) completed a comprehensive neuropsychological assessment battery on the Vienna Test System (VTS; CFADHD). Test performance allows the computation of 17 embedded performance validity indicators (PVTs) derived from eight different neuropsychological tests. Further, all participants completed several self- and other-report symptom rating scales assessing depressive symptoms and cognitive functioning. The Conners' Adult ADHD Rating Scale and the Beck Depression Inventory-II were administered to derive embedded symptom validity measures (SVTs). (4) Results and conclusion: Noncredible performance occurs in a sizeable proportion of about 10% up to 30% of individuals throughout the entire battery. Tests for attention and concentration appear to be the most adequate and sensitive for detecting underperformance. Cognitive underperformance represents a coherent construct and seems dissociable from symptom overreporting. These results emphasize the importance of performing multiple PVTs, at different time points, and promote more accurate calculation of the positive and negative predictive values of a given validity measure for noncredible performance during clinical assessments. Future studies should further examine whether and how the present results stand in other clinical populations, by implementing rigorous reference standards of noncredible performance, characterizing those failing PVT assessments, and differentiating between underlying motivations.

The dynamics of social activation and suspiciousness in individuals at ultra-high risk for psychosis.

INTRODUCTION: Social functioning is often impaired during the ultra-high risk (UHR) phase for psychosis, but group-level studies regarding the role of social functioning in transition to psychosis are inconsistent. Exploring the inter-individual differences which underlie the association between social functioning and psychotic symptoms in this phase could yield new insights. OBJECTIVE: To examine the idiographic and dynamic association between social activation and suspiciousness in individuals at UHR for psychosis using time-series analysis. METHODS: Twenty individuals at UHR for psychosis completed a diary application every evening for 90 days. Two items on social activation (quantity: 'time spent alone' and quality: 'feeling supported') and two items on suspiciousness ('feeling suspicious' and 'feeling disliked') were used. Time series (T = 90) of each individual were analyzed using vector auto regression analysis (VAR), to estimate the lagged (over 1 day) effect of social activation on suspiciousness, and vice versa, as well as their contemporaneous associations. RESULTS: Heterogeneous person-specific associations between social activation and suspiciousness were found in terms of strength, direction and temporal aspects. CONCLUSIONS: The association between social activation and suspiciousness differs amongst individuals who are at UHR for psychosis. These findings underline the importance of tailoring psychosocial interventions to the individual. Future studies may examine whether using results of single-subject studies in clinical practice to personalize treatment goals leads to better treatment outcomes.

Self-stigma and cognitive insight in individuals at ultra-high risk for psychosis.

Background: Impaired cognitive insight and increased self-stigma have been consistently reported in individuals diagnosed with schizophrenia spectrum disorders, but little is known about its presence in individuals at ultra-high risk of developing a psychosis, although self-stigma is associated with transition.to psychosis. The current study examined whether self-stigma is already present in individuals at ultra-high risk of psychosis, and whether this is associated with impaired cognitive insight. Methods: 184 participants were recruited divided over three groups, namely individuals diagnosed with a schizophrenia spectrum disorder (SSD; n = 92, 34% females), individuals at ultra-high risk for psychosis (UHR; n = 43, 59% females) and general population controls (GPC; n = 49, 27% females). All participants completed assessments on demographic information (gender, age, education), and cognitive insight. In addition, participants with SSD and individuals at UHR completed a questionnaire on self-stigma. Results: The level of self-stigma did not differ between individuals at UHR and individuals diagnosed with SSD. Cognitive insight also did not differ significantly between the three groups, but the subscale self-reflection differed between the three groups [F(2,184) = 4.20, p = 0.02], with the UHR and SSD groups showing more self-reflection. Pearson's correlation analyses showed that in individuals at UHR total cognitive insight and its self-reflection subscale were significantly associated with the alienation subscale of self-stigma, and in individuals with SSD self-certainty subscale of cognitive insight was significantly associated with stereotype endorsement. Conclusion: Findings show that self-stigma was already present in the UHR phase, to a similar degree as in individuals with a diagnosis of a SSD, and is thus not dependent of previous experience of having a label of SSD. Cognitive insight in individuals at UHR of psychosis appears to be intact, but individuals at UHR showed more self-reflectiveness, and individuals at risk with high cognitive insight also experience high levels of self-stigma. Overall findings from our study suggest that pre-emptive interventions targeting self-stigma, while considering cognitive insight, are needed early on in manifestation of psychotic illness, preferably already in the UHR phase.

Trajectories of Emotion Recognition Training in Virtual Reality and Predictors of Improvement for People with a Psychotic Disorder.

Meta-analyses have found that social cognition training (SCT) has large effects on the emotion recognition ability of people with a psychotic disorder. Virtual reality (VR) could be a promising tool for delivering SCT. Presently, it is unknown how improvements in emotion recognition develop during (VR-)SCT, which factors impact improvement, and how improvements in VR relate to improvement outside VR. Data were extracted from task logs from a pilot study and randomized controlled trials on VR-SCT (n = 55). Using mixed-effects generalized linear models, we examined the: (a) effect of treatment session (1-5) on VR accuracy and VR response time for correct answers; (b) main effects and moderation of participant and treatment characteristics on VR accuracy; and (c) the association between baseline performance on the Ekman 60 Faces task and accuracy in VR, and the interaction of Ekman 60 Faces change scores (i.e., post-treatment - baseline) with treatment session. Accounting for the task difficulty level and the type of presented emotion, participants became more accurate at the VR task (b = 0.20, p < 0.001) and faster (b = -0.10, p < 0.001) at providing correct answers as treatment sessions progressed. Overall emotion recognition accuracy in VR decreased with age (b = -0.34, p = 0.009); however, no significant interactions between any of the moderator variables and treatment session were found. An association between baseline Ekman 60 Faces and VR accuracy was found (b = 0.04, p = 0.006), but no significant interaction between difference scores and treatment session. Emotion recognition accuracy improved during VR-SCT, but improvements in VR may not generalize to non-VR tasks and daily life.

Measuring recovery in participants with a schizophrenia spectrum disorder: validation of the Individual Recovery Outcomes Counter (I.ROC).

BACKGROUND: To improve recovery in mental health, validated instruments are needed. AIMS: This study evaluates psychometric properties of the Individual Recovery Outcomes Counter (I.ROC) in a Dutch population of participants with a schizophrenia spectrum disorder (SSD). METHODS: 326 participants completed the I.ROC at baseline (n = 326), six months (n = 155) and twelve months (n = 84) as part of a routine outcome assessment. Reliability, validity, sensitivity to change, and internal factor structure were examined. RESULTS: Participants evaluated the I.ROC as comprehensive. Internal consistency of the I.ROC (α = 0.88) and test-retest reliability (r = .85, p < .001) are good. Negative moderate correlations with the total score of the PANSS (r=-.50, p < .001) and the HoNOS (r=-.52, p < .001) were found, and a small negative correlation with the FR tool (r=-.36, p < .001). Moderate positive correlation with the MANSA (r = .55, p < .001) and the RAS (r = .60, p < .001) were found. The mean total I.ROC scores increased significantly between time points (F(2,166) = 6.351, p < .005), although differences were small. Confirmatory factor analysis showed that fit indices for the one-, two-, and four-factor model are comparable. CONCLUSIONS: The I.ROC is a valid and reliable instrument, with sensitivity to change, to map recovery in participants with SSD.

Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

BEATVIC, a body-oriented resilience therapy for individuals with psychosis: Short term results of a multi-center RCT.

BACKGROUND: Individuals with a psychotic disorder are at an increased risk of victimization, but evidenced-based interventions are lacking. AIMS: A body-oriented resilience therapy ('BEATVIC') aimed at preventing victimization was developed and its effectiveness was assessed in a multicenter randomized controlled trial. METHODS: 105 people with a psychotic disorder were recruited from six mental health centers. Participants were randomly allocated to 20 BEATVIC group sessions (n = 53) or befriending group sessions (n = 52). Short term effects on risk factors for victimization (e.g. social cognitive deficits, inadequate interpersonal behavior, low self-esteem, internalized stigma, aggression regulation problems), physical fitness and secondary outcomes were expected. At six-month follow-up, the effect on victimization (either a 50% reduction or an absence of victimization incidents) was examined. RESULTS: Intervention-dropout was 28.30% for BEATVIC and 39.62% for befriending. In both conditions the majority of participants (60.5% BEATVIC vs 62.9% befriending) showed a reduction or absence of victimization incidents at six months follow-up, which was not significantly different according to condition. Multilevel analyses revealed no main effect of time and no significant time x group interaction on other outcome measures. Per protocol analyses (participants attending ≥ 75% of the sessions) did not change these results. CONCLUSIONS: Although a reduction or absence of victimization was found at short term follow-up for the majority of participants, BEATVIC was not more effective than the active control condition. No short-term additional effects on risk factors of victimization were found. Analysis of the data at 2-year follow-up is warranted to investigate possible effects in the long-term. TRIAL REGISTRATION NUMBER: Current Controlled Trials: ISRCTN21423535.

Insight does not come at random: Individual gray matter networks relate to clinical and cognitive insight in schizophrenia.

BACKGROUND: Impaired clinical and cognitive insight are prevalent in schizophrenia and relate to poorer outcome. Good insight has been suggested to depend on social cognitive and metacognitive abilities requiring global integration of brain signals. Impaired insight has been related to numerous focal gray matter (GM) abnormalities distributed across the brain suggesting dysconnectivity at the global level. In this study, we test whether global integration deficiencies reflected in gray matter network connectivity underlie individual variations in insight. METHODS: We used graph theory to examine whether individual GM-network metrics relate to insight in patients with a psychotic disorder (n = 114). Clinical insight was measured with the Schedule for the Assessment of Insight-Expanded and item G12 of the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Individual GM-similarity networks were created from GM-segmentations of T1-weighted MRI-scans. Graph metrics were calculated using the Brain Connectivity Toolbox. RESULTS: Networks of schizophrenia patients with poorer clinical insight showed less segregation (i.e. clustering coefficient) into specialized subnetworks at the global level. Schizophrenia patients with poorer cognitive insight showed both less segregation and higher connectedness (i.e. lower path length) of their brain networks, making their network topology more "random". CONCLUSIONS: Our findings suggest less segregated processing of information in patients with poorer cognitive and clinical insight, in addition to higher connectedness in patients with poorer cognitive insight. The ability to take a critical perspective on one's symptoms (clinical insight) or views (cognitive insight) might depend especially on segregated specialized processing within distinct subnetworks.

Neural changes following a body-oriented resilience therapy with elements of kickboxing for individuals with a psychotic disorder: a randomized controlled trial.

Individuals with a psychotic disorder are at an increased risk of becoming the victim of a crime. A body-oriented resilience therapy (BEATVIC) aimed at preventing victimization by addressing putatively underlying factors was developed. One of these factors is social cognition, particularly facial affect processing. The current study investigated neural effects of BEATVIC on facial affect processing using two face processing tasks. Participants were randomized to either BEATVIC or a 'Befriending' control group. Twenty-seven patients completed an Emotional Faces task and the Wall of Faces task during fMRI, pre- and post-intervention. General linear model analyses yielded no differences between groups over time. Independent component analyses revealed increased activation of the salience network to angry and fearful faces in BEATVIC compared to Befriending. Increased activation of the salience network may suggest an increased alertness for potentially dangerous faces.

The clinical relevance of early identification and treatment of sleep disorders in mental health care: protocol of a randomized control trial.

BACKGROUND: Sleep disorders are a risk factor for developing a variety of mental disorders, have a negative impact on their remission rates and increase the risk of relapse. Early identification and treatment of sleep disorders is therefore of paramount importance. Unfortunately, in mental health care sleep disorders are often poorly recognized and specific treatment frequently occurs late or not at all. This protocol-paper presents a randomized controlled trial investigating the clinical relevance of early detection and treatment of sleep disorders in mental health care. The two aims of this project are 1) to determine the prevalence of sleep disorders in different mental disorders, and 2) to investigate the contribution of early identification and adequate treatment of sleep disorders in individuals with mental disorders to their sleep, mental disorder symptoms, general functioning, and quality of life. METHODS: Patients newly referred to a Dutch mental health institute for psychiatric treatment will be screened for sleep disorders with the self-assessment Holland Sleep Disorders Questionnaire (HSDQ). Patients scoring above the cut-off criteria will be invited for additional diagnostic evaluation and, treatment of the respective sleep disorder. Participants will be randomly assigned to two groups: Immediate sleep diagnostics and intervention (TAU+SI-T0), or delayed start of sleep intervention (TAU+SI-T1; 6 months after inclusion). The effect of sleep treatment as add-on to treatment as usual (TAU) will be tested with regard to sleep disorder symptoms, general functioning, and quality of life (in collaboration with a psychiatric sleep centre). DISCUSSION: This trial will examine the prevalence of different sleep disorders in a broad range of mental disorders, providing information on the co-occurrence of specific sleep and mental disorders. Further, this study is the first to investigate the impact of early treatment of sleep disorders on the outcome of many mental disorders. Moreover, standard sleep interventions will be tailored to specific mental disorders, to increase their efficacy. The results of this trial may contribute considerably to the improvement of mental health care. TRIAL REGISTRATION: This clinical trial has been retrospectively registered in the Netherlands Trial Register (NL8389; https://www.trialregister.nl/trial/8389) on February 2th, 2020.

A cognitive remediation training for young adults with psychotic disorders to support their participation in education - study protocol for a pilot randomized controlled trial.

BACKGROUND: Most severe mental disorders have their onset between the age of 17 and 27, a time when many young adults begin participating in secondary or post-secondary education. The cognitive deficits typically associated with psychiatric disorders, especially psychotic disorders, increase the risk of leaving school early, which can lead to a reduction in employment opportunities later on in life and, in turn, a poorer long-term prognosis. Therefore, specific interventions aiming to improve these cognitive functions are needed. Cognitive remediation (CR) aims to improve cognitive functioning and may increase real-world functioning in educational performance. This study aims to examine the feasibility and applicability of a CR training named Mindset for students with psychotic disorders in the Netherlands. METHODS/DESIGN: Sixty students diagnosed with a psychotic disorder and currently reporting cognitive deficits will be included from four Dutch Mental Health Care institutes. Half of the participants (N = 30) will be randomly assigned to the CR training consisting of twelve, individual, weekly 1-h meetings. The other half will be assigned to an active control condition consisting of twelve weekly assignments that will be sent by email aiming to improve school performance. Students will be evaluated at baseline (T0), directly after finishing the CR training or control intervention (T1), and 6 months later (T2). Treatment feasibility will be the primary outcome, using evaluation forms, interviews with trainers and participants, number of study drop outs, and patient eligibility and recruitment rates. School functioning, cognitive functioning, and strategy use will also be assessed to get a preliminary idea of the potential effectiveness of the intervention. DISCUSSION: The CR training in this study will provide real-world examples and exercises aimed to teach useful strategies to cope with the cognitive deficits experienced by students with psychotic disorders. Furthermore, since students with other psychiatric disorders might also experience cognitive deficits, the results of this study may also provide some further implications for future studies on the effect of this CR training for students with these disorders. TRIAL REGISTRATION: The study was registered with Trialregister.nl, no. NL6590 (NTR6764), date registered: September 7, 2017. Register name: Mindset. A cognitive rehabilitation training for young adults with psychotic spectrum disorder in an educational setting: A pilot study.Protocol version: 3, date December 23, 2019.

Social Cognition Training for People With a Psychotic Disorder: A Network Meta-analysis.

Deficits in social cognition are common in people with psychotic disorders and negatively impact functioning. Social Cognition Training (SCT) has been found to improve social cognition and functioning, but it is unknown which interventions are most effective, how characteristics of treatments and participants moderate efficacy, and whether improvements are durable. This meta-analysis included 46 randomized studies. SCTs were categorized according to their focus (targeted/broad-based) and inclusion of cognitive remediation therapy (CRT). Network meta-analysis was conducted, using both direct (original) and indirect (inferred from the network of comparisons) evidence. All SCT types were compared to treatment as usual (TAU; the chosen reference group). Moderators of outcome were investigated with meta-regression and long-term efficacy with multivariate meta-analysis. Compared to TAU, emotion perception was improved by targeted SCT without CRT (d = 0.68) and broad-based SCT without CRT (d = 0.46). Individual treatments worked better for emotion perception. All treatments significantly improved social perception (active control, d = 0.98, targeted SCT with and without CRT, d = 1.38 and d = 1.36, broad-based SCT with and without CRT, d = 1.45 and d = 1.35). Only broad-based SCT (d = 0.42) improved ToM. Broad-based SCT (d = 0.82 without and d = 0.41 with CRT) improved functioning; group treatments worked significantly better. Male gender was negatively related to effects on social functioning and psychiatric symptoms. At follow-up, a moderate effect on social functioning (d = 0.66) was found. No effect was found on attribution, social cognition (miscellaneous), and psychiatric symptoms. While targeted SCT is the most effective for emotion perception and social perception, broad-based SCT produces the best overall outcomes. CRT did not enhance SCT effects.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

The Longitudinal Association Between Preadolescent Facial Emotion Identification and Family Factors, and Psychotic Experiences in Adolescence (The TRAILS Study).

The current study examines whether facial emotion identification and family factors at preadolescence (age 11) predict psychotic experiences 5 years later during adolescence (age 16) and whether family factors may mediate the association between facial emotion identification and psychotic experiences. Data was obtained from the epidemiological cohort TRAILS (N = 2059). At preadolescence, a facial emotion identification test and three questionnaires to assess family functioning, perceived parenting styles and parenting stress, were administered. At adolescence, a questionnaire on psychotic experiences was administered. Facial emotion identification at preadolescence was not associated with psychotic experiences at adolescence, and the mediational role of family functioning was not further explored. However, increased overprotective parenting at preadolescence was associated with a higher frequency of psychotic experiences and delusions at adolescence. Future research may examine the mechanism behind the role of overprotective parenting on psychotic experiences during adolescence.

Onset and transition of and recovery from adverse development: Study methodology.

AIM: Early intervention programs for first-episode psychosis have led to the awareness that the period before onset of a first episode is important in light of early intervention. This has induced a focus on the so-called 'at risk mental state' (ARMS). Individuals with ARMS are at increased risk for later psychotic disorder, but also for other psychiatric disorders as well as poor psychosocial functioning. Thus, adequate detection and treatment of ARMS is essential. METHODS: Since 2018, screening for and treatment of ARMS is recommended standard care in the Netherlands. Implementation is still ongoing. We initiated a naturalistic long-term cohort study of ARMS individuals, the onset and transition of and recovery from adverse development (OnTheROAD) study, with the aim to monitor course and outcome of symptoms and psychosocial functioning over time, as well as patterns of comorbidity and associations with factors of risk and resilience. To this end, participants complete a broad battery of instruments at baseline and yearly follow-up assessments up to 3 years. Outcome is defined in terms of symptom severity level, functioning and quality of life. In particular, we aim to investigate the impact of negative symptoms as part of the ARMS concept. Results from this study can aid in refining the existing ARMS criteria, understanding the developmental course of ARMS and investigating the hypothesized pluripotentiality in outcome of ARMS. New knowledge may inform the further development of specialized early interventions. RESULTS AND CONCLUSIONS: In this article, we describe the rationale, outline and set-up of OnTheROAD.

Neural correlates of victimization in psychosis: differences in brain response to angry faces.

Individuals with psychosis are at an increased risk of victimization. Processing of facial expressions has been suggested to be associated with victimization in this patient group. Especially processing of angry expressions may be relevant in the context of victimization. Therefore, differences in brain activation and connectivity between victimized and nonvictimized patients during processing of angry faces were investigated. Thirty-nine patients, of whom nineteen had experienced threats, assaults, or sexual violence in the past 5 years, underwent fMRI scanning, during which they viewed angry and neutral facial expressions. Using general linear model (GLM) analyses, generalized psychophysiological (gPPI) analysis and independent component analyses (ICA) differences in brain activation and connectivity between groups in response to angry faces were investigated. Whereas differences in regional brain activation GLM and gPPI analyses yielded no differences between groups, ICA revealed more deactivation of the sensorimotor network in victimized participants. Deactivation of the sensorimotor network in response to angry faces in victimized patients, might indicate a freeze reaction to threatening stimuli, previously observed in traumatized individuals.

Dynamic Interactive Social Cognition Training in Virtual Reality (DiSCoVR) for social cognition and social functioning in people with a psychotic disorder: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Problems in social functioning (e.g., unemployment, social isolation), are common in people with a psychotic disorder. Social cognition is a treatment target to improve social functioning, as it is a proximal predictor of social functioning. Social Cognition Training (SCT) improves social cognition, but may not generalize (enduringly) to social functioning, perhaps due to insufficient opportunity to practice in daily-life social situations. Using virtual reality (VR) for SCT could address this problem, as VR is customizable, accessible, and interactive. We will test the effect of a VR SCT, 'DiSCoVR', on social cognition and social functioning in a randomized controlled trial (RCT). METHODS: In total 100 people with a psychotic disorder and deficits in social cognition will be recruited for this multicenter randomized controlled trial (RCT). Participants will be randomized to VR SCT (DiSCoVR) or VR relaxation training (VRelax; active control). DiSCoVR is a 16-session individual SCT, consisting of three modules: 1) emotion perception (recognizing facial emotions in a virtual shopping street); 2) social perception and theory of mind (observing social interactions between virtual characters and assessing their behavior, emotions and thoughts); and 3) application of higher-order social cognition in social interaction (role-playing personalized situations in VR). People receiving VRelax complete sixteen individual sessions, in which they receive psycho-education about stress, identify personal stressors, learn relaxation techniques, and explore relaxing immersive virtual environments. Assessments will be performed at baseline, post-treatment, and 3-month follow-up. Primary outcomes are emotion perception (Ekman 60 Faces), social perception and theory of mind (The Awareness of Social Inference Test). Secondary outcomes include social functioning (Personal and Social Performance Scale), experiences and social interactions in daily life (experience sampling of emotions, social participation and subjective experience of social situations), psychiatric symptoms (e.g., depression, perceived stress, anxiety, positive and negative symptoms) and self-esteem. DISCUSSION: To our knowledge, this will be the first RCT testing the efficacy of VR SCT. It will also investigate generalization to daily life social situations, the durability of treatment effects, and moderators and mediators of treatment success. TRIAL REGISTRATION: On December 5, 2017, this trial was registered prospectively in the Dutch Trial Register as NTR6863 .