The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Efficacy of Acceptance and Commitment Therapy in Daily Life in Early Psychosis: Results from the Multi-Center INTERACT Randomized Controlled Trial.

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; p<0.001) improved in ACT-DL+TAU compared to TAU, as did momentary psychotic distress (χ2(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.

Intact striatal dopaminergic modulation of reward learning and daily-life reward-oriented behavior in first-degree relatives of individuals with psychotic disorder.

BACKGROUND: Abnormalities 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: These 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.

Neural correlates of daily-life affective stress reactivity in early psychosis: A study combining functional MRI and experience sampling methodology.

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.

Efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL) in early psychosis: study protocol for a multi-centre randomized controlled trial.

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

Ecological momentary interventions in psychiatry.

PURPOSE OF REVIEW: In this review, we discuss feasibility, content, and where possible efficacy of ecological momentary interventions (EMIs) in psychiatry. EMIs adopt mobile devices, such as personal digital assistants or smartphones, for the delivery of treatments in the daily life of patients. We will discuss EMIs in the field of schizophrenia, bipolar disorder and major depression disorder, as well as one generic, transdiagnostic EMI. RECENT FINDINGS: The few studies that are available all underscore feasibility and acceptability of mobile health approaches in patients with severe mental illness. In terms of content, there is a huge variety in approaches ranging from a mixture of face-to-face contacts augmented with EMI components to a fully automated EMI. With regard to efficacy, only two randomized clinical trials have been conducted, supporting the efficacy of EMIs in mental health. Evidence seems to point toward greater efficacy when EMI is integrated with real-life assessment using experience sampling methodology, preferentially tailoring the intervention toward the specific needs of the individual as well as toward those moments when intervention is needed. SUMMARY: The review demonstrates that mobile health may be an important asset to the mental health field but underscores that it still is in its very early ages. In the discussion, we point toward ways of improving EMIs for severe mental illness, changing our perspective from testing feasibility to testing efficacy and ultimately implementing EMIs in routine mental health services.