Identifying and treating predictors of psychotic symptoms - How findings from Experience Sampling research can help to improve the treatment of psychosis and the prediction of relapse

The present thesis aims at using insights from ESM studies (i.e., frequent ecologically valid self-reports for approximately one week) to improve the treatment and the prediction psychotic symptoms. ESM indicates that warning signs, such as negative affect, worrying, sleep problems, or aberrant salience precede rapidly fluctuating psychotic symptoms throughout the day. Assuming underlying causal associations, we developed an Internet intervention called EviBaS that targets ESM-derived warning signs to improve psychotic symptoms (studies 1-3). Further, we examined said warning signs as candidate predictors of psychotic relapses (study 4). EviBaS improved positive symptoms compared to a waitlist condition (p = .047, d = -0.37) in a randomized controlled trial (study 1, n = 101). Mixed model analyses (study 2; n = 124) indicated that this effect did not rely on improving ESM-based predictors, as their course did not differ between groups. However, worrying (p = .030) and quality of sleep (p = .003) predicted subsequent psychotic symptoms during the intervention, indicating that they would have been worthwhile treatment targets. Whereas worrying and sleep were unrelated to EviBaS’ efficacy, mindfulness emerged as a possible mechanism of change. In voice hearers (n = 55), completing the EviBaS-mindfulness module improved hallucinations (p = 0.001, ηp2 = 0.214), mediated by mindfulness. Study 4 incorporated a one-week ESM phase followed by bi-weekly assessments over one year (n = 30). Negative affect (p = .003) and aberrant salience (p < .001) predicted short-term paranoia but only aberrant salience remained a predictor of bi-weekly paranoia (p < .001). No variable predicted relapse. In sum, this thesis shows that ESM findings offer promising starting points to improve the treatment and the prediction of psychotic symptoms. It seems worthwhile to improve EviBaS to target a wider range of outcomes. Further, we should examine aberrant salience in sufficiently powered relapse-prediction studies

A randomized controlled trial on a smartphone self-help application (Be Good to Yourself) to reduce depressive symptoms

Accepted manuscript version, licensed CC BY-NC-ND 4.0. Published version available at https://doi.org/10.1016/j.psychres.2018.08.113.Depressive symptoms are common, yet only a subgroup of individuals receive adequate treatment. To reduce the treatment gap, several online self-help programs have been developed, yielding small to moderate effects. We developed a smartphone self-help application addressing depressive symptoms. We sought to evaluate its feasibility and efficacy in participants reporting a subjective need for help (a diagnosis of depression was not mandatory). We conducted a randomized controlled trial (N = 90). The primary outcome was a reduction of depressive symptoms measured with the Patient Health Questionnaire-9 (PHQ-9). Secondary outcomes included improved self-esteem (Rosenberg Self-Esteem Scale) and quality of life (WHOQOL-BREF). The intervention group obtained access to the application for four weeks, the wait-list group received access after the post assessment. No group differences emerged in either outcome in intention-to-treat analyses. Per protocol analyses with frequent users (i.e., several times a week or more) yielded a small effect size (η2p = 0.049) at trend level on the reduction of depressive symptoms in favor of the treatment group. However, 39% of the participants did not use the application frequently. Mobile self-help applications represent a promising addition to existing treatments, but it is important to increase patients’ motivation to use them

Prolonged rather than hasty decision-making in schizophrenia using the box task. Must we rethink the jumping to conclusions account of paranoia?

Accepted manuscript version, licensed CC BY-NC-ND 4.0. Jumping to conclusions (JTC) is the best established cognitive bias in schizophrenia and is increasingly targeted in interventions aimed to improve positive symptoms. To address shortcomings of the standard measure to capture JTC, the beads task, we developed a new variant—the box task—which was subsequently validated in people with elevated psychotic-like experiences. For the first time, the box task was administered in a sample of individuals with manifest schizophrenia. We hypothesized that patients with schizophrenia would display an elevated JTC bias relative to controls. Method - We recruited a large sample of 101 patients with schizophrenia and matched them to an online sample recruited from the general population. In the box task, participants must decide which of two kinds of colored balls are presented more often. Participants are told that the task may end prematurely, and that task performance will be counted as an error if no decision had been made before that point. The primary measure was the number of draws to decision (DTD), where fewer DTD corresponds to greater JTC. Results - In contrast to expectations, participants with schizophrenia showed significantly higher DTD (i.e., reduced JTC). Consistent with our previous findings, patients also displayed a lowered decision threshold compared to controls. Response confidence for the final decision was lower in patients and correlated with self-esteem and positive symptoms. While there was evidence that previous knowledge of the box task lowered DTD, exclusion of participants with experience on the box task did not substantially change results. Discussion - The study fits a growing body of experiments casting doubt on the generalizability of the JTC effect in schizophrenia across different tasks. While the study tentatively supports a liberal acceptance account of psychosis, caution is warranted and we recommend that research should explore and control for potentially important mediators (e.g., task difficulty, stress, test-taking attitudes)

Negative expectations regarding interpersonal interactions in daily life are associated with subclinical depressive symptoms in a student sample: A prospective experience sampling study

Background. Dysfunctional expectations and interpersonal problems are central aspects of depression, but expectations regarding everyday-life interpersonal interactions have not been studied, yet. Using Experience Sampling, we measured expected emotions towards interaction partners and compared them with actual emotions. We hypothesized that stable negative expectations would predict sub-clinical depression and negative affect. Methods. Fifty-three students completed six days of Experience Sampling, consisting of one morning assessment on expectations regarding anticipated interpersonal interactions (9am), three assessments on actual interpersonal experiences (1pm, 5pm, 9pm), and six pseudo-random affect assessments. We compared expected emotions, experienced emotions, and day-to-day fluctuations of expectations between individuals with high versus low sub-clinical depression (median split). Using mixed models, we examined whether negative expectations preceded negative affect, and whether expectation violations preceded adjustments of expectations. Results. Individuals with higher depression expected more negative emotions, even after controlling for negative experiences, and surprisingly more variable expectations. In mixed models, neither momentary expectations nor experiences preceded negative affect, but worse-than-expected interpersonal interactions did. Better-than-expected interactions predicted reductions of negative expectations, but less so in the high-depression group. Conclusions. Our findings are limited by the non-clinical sample and skewed data. Nonetheless, our approach appears well-suited to examine idiosyncratic interpersonal expectations in vivo

Mindfulness Mediates the Effect of a Psychological Online Intervention for Psychosis on Self-Reported Hallucinations: A Secondary Analysis of Voice Hearers From the EviBaS Trial

Background Psychological online interventions (POIs) could represent a promising approach to narrow the treatment gap in psychosis but it remains unclear whether improving mindfulness functions as a mechanism of change in POIs. For the present study, we examined if mindfulness mediates the effect of a comprehensive POI on distressing (auditory) hallucinations. Methods We conducted a secondary analysis on voice hearers (n = 55) from a randomized controlled trial evaluating a POI for psychosis (EviBaS; trial registration NCT02974400, clinicaltrials.gov). The POI includes a module on mindfulness and we only considered POI participants in our analyses who completed the mindfulness module (n = 16). Results Participants who completed the mindfulness module reported higher mindfulness (p = 0.015) and lower hallucinations (p = 0.001) at post assessment, compared to controls, but there was no effect on distress by voices (p = 0.598). Mindfulness mediated the POI’s effect on hallucinations (b = −1.618, LLCI = −3.747, ULCI = −0.054) but not on distress by voices (b = −0.057, LLCI = −0.640, ULCI = 0.915). Limitations and Discussion Completion of the mindfulness module was not randomized. Hence, we cannot draw causal inferences. Even if we assumed causality, it remains unclear which contents of the POI could have resulted in increased mindfulness and reduced hallucinations, as participants completed other modules as well. In addition, confounding variables could explain the mediation and the sample size was small. Nonetheless, the overall pattern of results indicates that the POI is likely to improve mindfulness, and that increased mindfulness could partially explain the POI’s efficacy. Keywords: mindfulness-based intervention, auditory verbal hallucinations, mediation analysis, schizophrenia, internet interventio

ESM

Predicting psychotic symptoms and relapse in psychosis: psychological precursors of psychosis in short-term and long-term experience sampling assessment

Insight and the number of completed modules predict a reduction of positive symptoms in an Internet-based intervention for people with psychosis

Emerging evidence suggests that Internet-based interventions for people with psychosis (ICBTp) are feasible and efficacious. However, predictors of adherence and treatment outcomes are largely unknown. To narrow this research gap, we conducted secondary analyses on data from a randomized controlled trial, which evaluated an eight-week ICBTp intervention targeting topics, such as voice hearing, mindfulness, and others. In n = 100 participants with psychosis, we aimed at identifying sociodemographic, psychopathological, and treatment-related predictor variables of post-treatment symptoms and adherence (i.e., at least four completed modules). We followed a two-stage approach. First, we conducted regression analyses to examine the effect of single candidate predictors on post-treatment symptoms as well as adherence. Subsequently, we selected variables that met a significance threshold of p < .1 and entered them into linear and logistic multiple regression models. Whereas no variable was able to predict adherence, the number of completed modules was negatively associated with self-reported delusion severity at post-treatment. Additionally, higher pre-treatment insight predicted fewer hallucinations after treatment. Because this was one of the first studies to investigate predictors in ICBTp, more research is needed to customize future interventions to the needs of users

Fighting Depression: Action Video Game Play May Reduce Rumination and Increase Subjective and Objective Cognition in Depressed Patients

Cognitive deficits are common in depression and may persist following the resolution of affective symptoms. However, therapeutic strategies that successfully target cognitive impairments are lacking. Recent work has demonstrated that playing action video games leads to improvements in cognition, in particular executive function, in healthy individuals. We therefore set out to test whether playing video games can reduce symptoms associated with depression. We focussed on depressive symptoms and on rumination, since rumination is a good predictor of depression and may contribute to triggering depression. We recruited 68 clinically depressed individuals (mean age: 46 years, 47 females) that were randomized into the training group playing a fast paced action video game for 6 weeks or a waitlist control group. Before and after training participants completed online questionnaires and a neuropsychological test battery. Only participants who actually played the game were included in the analysis. The final sample consisted of n = 21 training group and n = 29 waitlist control group. The training group showed significantly higher subjective cognitive ability, as well as lower self-reported rumination at posttest in contrast to the control group (although these findings do not survive Bonferroni correction). On a subsample with cognitive performance data (n = 19) we detected an improvement in executive function (Trail Making Task A and B) in the training compared with the control group. The results show that the fast paced action video game employed in the present study improved Trail Making performance and may reduce rumination and enhance subjective cognitive ability. Future research may focus on the investigation of the precise cognitive profile of effects