Applying multiverse analysis to experience sampling data: Investigating whether preprocessing choices affect robustness of conclusions.

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.

Elucidating negative symptoms in the daily life of individuals in the early stages of psychosis.

BACKGROUND: It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls. METHODS: We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls. RESULTS: Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat-risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality. CONCLUSIONS: Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.

Lower [18F]fallypride binding to dopamine D2/3 receptors in frontal brain areas in adults with 22q11.2 deletion syndrome: a positron emission tomography study.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels. METHODS: The study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure. RESULTS: BPND was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BPND in the orbitofrontal cortex and anterior cingulate cortex. CONCLUSIONS: This study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.

Investigating real-time social interaction in pairs of adolescents with the Perceptual Crossing Experiment.

The study of real-time social interaction provides ecologically valid insight into social behavior. The objective of the current research is to experimentally assess real-time social contingency detection in an adolescent population, using a shortened version of the Perceptual Crossing Experiment (PCE). Pairs of 148 adolescents aged between 12 and 19 were instructed to find each other in a virtual environment interspersed with other objects by interacting with each other using tactile feedback only. Across six rounds, participants demonstrated increasing accuracy in social contingency detection, which was associated with increasing subjective experience of the mutual interaction. Subjective experience was highest in rounds when both participants were simultaneously accurate in detecting each other's presence. The six-round version yielded comparable social contingency detection outcome measures to a ten-round version of the task. The shortened six-round version of the PCE has therefore enabled us to extend the previous findings on social contingency detection in adults to an adolescent population, enabling implementation in prospective research designs to assess the development of social contingency detection over time.

Exploring the feasibility and usability of the experience sampling method to examine the daily lives of patients with acquired brain injury.

The experience sampling method (ESM) is a structured diary method with high ecological validity, in that it accurately captures the everyday context of individuals through repeated measurements in naturalistic environments. Our main objective was to investigate the feasibility of using ESM in individuals with acquired brain injury (ABI). A second goal was to explore the usability of ESM data on a clinical level, by illustrating the interactions between person, environment, and affect. The PsyMate device provided ABI patients (N = 17) with ten signals (beeps) per day during six consecutive days. Each beep was followed by a digital questionnaire assessing mood, location, activities, social context, and physical well-being. Results demonstrated high feasibility with a 71% response rate and a 99% completion rate of the questionnaires. There were no dropouts and the method was experienced as user-friendly. Time-lagged multilevel analysis showed that higher levels of physical activity and fatigue predicted higher levels of negative affect at the same point in time, but not at later time points. This study illustrates the potential of ESM to identify complex person-environment dynamics after ABI, while generating understandable and easy to use graphical feedback.

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.

Using Experience Sampling Methods to support clinical management of psychosis: The perspective of people with lived experience.

The Experience sampling method (ESM) has the potential to support person-centered care of psychotic disorders. However, clinical implementation is hampered by a lack of user involvement in the design of ESM tools. This qualitative study explored the perspective of nine people with lived experiences of psychosis. Participants reported a need to monitor a diverse range of daily-life experiences and indicated that ESM should allow for personalization to be clinically useful. While participants recognized the potential of ESM to increase awareness and control over their mental health, concerns were voiced about the validity and burden of monitoring one's own mental health.

Ecological and Convergent Validity of Experimentally and Dynamically Assessed Capacity for Social Contingency Detection Using the Perceptual Crossing Experiment in Adolescence.

The Perceptual Crossing Experiment (PCE) captures the capacity for social contingency detection using real-time social interaction dynamics but has not been externally validated. We tested ecological and convergent validity of the PCE in a sample of 208 adolescents from the general population, aged 11 to 19 years. We expected associations between PCE performance and (a) quantity and quality of social interaction in daily life, using Experience Sampling Methodology (ESM; ecological validity) and (b) self-reported social skills using a questionnaire (convergent validity). We also expected PCE performance to better explain variance in ESM social measures than self-reported social skills. Multilevel analyses showed that only self-reported social skills were positively associated with social experience of company in daily life. These initial results do not support ecological and convergent validity of the PCE. However, fueled by novel insights regarding the complexity of capturing social dynamics, we identified promising methodological advances for future validation efforts.

Schizophrenia Patients Show Largely Similar Salience Signaling Compared to Healthy Controls in an Observational Task Environment.

Recent evidence suggests that the aberrant signaling of salience is associated with psychotic illness. Salience, however, can take many forms in task environments. For example, salience may refer to any of the following: (1) the valence of an outcome, (2) outcomes that are unexpected, called reward prediction errors (PEs), or (3) cues associated with uncertain outcomes. Here, we measure brain responses to different forms of salience in the context of a passive PE-signaling task, testing whether patients with schizophrenia (SZ) showed aberrant signaling of particular types of salience. We acquired event-related MRI data from 29 SZ patients and 23 controls during the performance of a passive outcome prediction task. Across groups, we found that the anterior insula and posterior parietal cortices were activated to multiple different types of salience, including PE magnitude and heightened levels of uncertainty. However, BOLD activation to salient events was not significantly different between patients and controls in many regions, including the insula, posterior parietal cortices, and default mode network nodes. Such results suggest that deficiencies in salience processing in SZ may not result from an impaired ability to signal salience per se, but instead the ability to use such signals to guide future actions. Notably, no between-group differences were observed in BOLD signal changes associated with PE-signaling in the striatum. However, positive symptom severity was found to significantly correlate with the magnitudes of salience contrasts in default mode network nodes. Our results suggest that, in an observational environment, SZ patients may show an intact ability to activate striatal and cortical regions to rewarding and non-rewarding salient events. Furthermore, reduced deactivation of a hypothesized default mode network node for SZ participants with high levels of positive symptoms, following salient events, point to abnormalities in interactions of the salience network with other brain networks, and their potential importance to positive symptoms.

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

Temporal associations between sleep quality and paranoia across the paranoia continuum: An experience sampling study.

Sleep disturbances are prevalent among individuals with a psychotic disorder and have been linked to symptoms of paranoia across the entire psychosis continuum. Emerging evidence suggests that rather than a secondary symptom, poor quality of sleep may contribute to elevated paranoid ideation. We investigated the temporal dynamics of sleep quality and paranoid ideation using the experience sampling method in 42 acutely paranoid individuals with a psychotic disorder, 32 nonparanoid individuals with psychotic disorder, and 41 individuals with high schizotypy traits. We applied time-lagged mixed multilevel modeling to tease apart the effect of poor sleep quality on morning paranoia and negative affect, and the impact of evening paranoid ideation and negative affect on subsequent sleep quality. In the whole sample, poor subjective sleep quality predicted elevated paranoia the following morning, a relationship that was fully mediated by morning negative affect. No significant association between evening paranoia and poor sleep the following night emerged. In the everyday lives of individuals on the paranoia continuum, low quality of sleep appears to drive paranoia through its impact on negative affect. These findings identify sleep quality as an important target of transdiagnostic interventions for psychotic and affective symptomatology. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Affective and psychotic reactivity to daily-life stress in adults with 22q11DS: a study using the experience sampling method.

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.

Temporal dynamics of suspiciousness and hallucinations in clinical high risk and first episode psychosis.

The objective of the current study is to elucidate the temporal dynamics of suspiciousness and hallucinations as they occur in daily life in the early stages of psychosis. Their prevalence and co-occurrence, as well as their temporal relation to affect and delusions, were compared between patients with a first psychotic episode (FEP) and individuals at clinical high risk for psychosis (CHRp). The Experience Sampling Method was used to investigate suspiciousness and hallucinatory experiences, delusions, and affect at semi-random moments throughout six days in 33 CHRp and 34 FEP. Overall, 91% of CHRp and 59% of FEP reported suspiciousness, and 24% and 39% reported hallucinations, respectively. Hallucinations almost always co-occurred with suspiciousness, whereas suspiciousness was often present without hallucinations. Suspicious episodes in CHRp occurred with marked increases in delusional intensity, while hallucinatory experiences were mostly absent. In FEP, a decrease of positive affect preceded suspicious episodes, while an increase of negative affect preceded hallucinatory episodes. Our results indicated the presence of a delusional mood (atmosphere) in CHRp as an experience in itself, without co-occurring or following hallucinations, thus refuting the anomalous experience hypothesis of psychosis. The co-occurrence of hallucinations, on the other hand, indicates a more severe stage of symptomatology.

Lower cortisol levels and attenuated cortisol reactivity to daily-life stressors in adults with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with neurodevelopmental, anxiety and mood disorders, as well as an increased risk for developing psychosis. Cortisol levels and stress reactivity reflect hypothalamic-pituitary-adrenal (HPA)-axis activity, and are believed to be altered in individuals that often experience daily-life stress, depression, and psychotic symptoms. However, it is unknown whether individuals with 22q11DS display an altered stress reactivity. METHODS: We included 27 adults with 22q11DS (mean age: 34.1 years, 67% female) and 24 age and sex-matched healthy controls (HC; mean age: 39.9 years, 71% female) into an experience sampling study. Throughout 6 consecutive days, we measured participants' subjective stress related to current activity and at the same time collected salivary cortisol samples. Multilevel regression models were used to analyze cortisol reactivity to activity-related stress. RESULTS: Diurnal cortisol levels were significantly lower in the 22q11DS group compared to HCs (B=-1.03, p < 0.001). 22q11DS adults displayed significantly attenuated cortisol reactivity to activity-related stress compared to HCs (B = -0.04, p = 0.026). Post-hoc exploratory analysis revealed that these results were independent from 22q11DS psychiatric diagnosis or medication use. CONCLUSION: These results indicate that adults with 22q11DS have lower cortisol levels and attenuated cortisol response to daily stress, possibly resulting from an increased sensitization of the HPA-axis. This suggests that alterations in HPA-axis functioning, previously reported in several psychiatric disorders including post-traumatic stress disorder (PTSD), psychotic disorder, and mood disorder, also appear to be present in adults with 22q11DS.

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.

Recovery from daily-life stressors in early and chronic psychosis.

Initial affective and psychotic reactivity to daily stressors is altered in psychosis, and most notably in early psychosis. In addition to altered initial stress reactivity, results from studies using Experience Sampling Methodology (ESM) and psychophysiological measures indicate that impaired recovery from mild stressors may also be a risk factor for mental illness. The current ESM study investigated affective recovery from daily stressors in chronic psychosis patients (CP; n = 162), individuals at early stages of psychosis (EP; n = 127), and healthy volunteers (HV; n = 220) assessing fluctuations in negative affect (NA), tension, and suspiciousness ten times a day on six consecutive days. Recovery was operationalized for all three variables as the return to baseline (i.e., level at t-1) following the first stressful event of a day (i.e., t0). The EP group showed a delayed recovery of NA (t1-t3: B = 0.185; p = .007 and B = 0.228; p = .002) and suspiciousness (t1: B = 0.223; p = .010 and B = 0.291; p = .002) compared to HV and CP, respectively. Delayed recovery was detected for tension as well (t1-t2: EP > HV: B = 0.242; p = .040 and EP > CP: B = 0.284; p = .023), but contrary to both other momentary states, this effect disappeared when controlling for subsequent stressful events. There were no significant differences in recovery between HV and CP. These results suggest that in EP, stressful daily events have longer-lasting effects on overall negative affect and subclinical psychotic-like experiences. Future studies should incorporate physiological and endocrine measures in order to integrate recovery patterns of the different stress systems.

Social anhedonia and asociality in psychosis revisited. An experience sampling study.

The DSM-5 appended the conceptualization of asociality in psychotic disorders as the manifestation of diminished interest in social interactions, but it also admitted that it might merely be the result of limited opportunities for social interactions. In an effort to investigate this apparent dichotomy, we used experience sampling data from 149 patients with psychotic disorder and 143 controls, and divided their social interactions into those occurring in the context of work and other structured activities that patients have limited access to, and those occurring in the context of unstructured activities such as visits and conversations that both groups can choose relatively more freely. Patients spent significantly smaller proportion of their time in structured social context, but matched the controls in the time spent in unstructured social contexts, and endorsed intact hedonic experience of both social contexts. Moreover, employment and living situation, in addition to the severity of symptoms of avolition, predicted the proportion of time patients spent in structured and unstructured social contexts, supporting the notion that both lifestyle as well as disease-specific factors contribute to real-life social behavior in psychosis.

Overall cortisol, diurnal slope, and stress reactivity in psychosis: An experience sampling approach.

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.

Experience sampling methodology in mental health research: new insights and technical developments.

In the mental health field, there is a growing awareness that the study of psychiatric symptoms in the context of everyday life, using experience sampling methodology (ESM), may provide a powerful and necessary addition to more conventional research approaches. ESM, a structured self-report diary technique, allows the investigation of experiences within, and in interaction with, the real-world context. This paper provides an overview of how zooming in on the micro-level of experience and behaviour using ESM adds new insights and additional perspectives to standard approaches. More specifically, it discusses how ESM: a) contributes to a deeper understanding of psychopathological phenomena, b) allows to capture variability over time, c) aids in identifying internal and situational determinants of variability in symptomatology, and d) enables a thorough investigation of the interaction between the person and his/her environment and of real-life social interactions. Next to improving assessment of psychopathology and its underlying mechanisms, ESM contributes to advancing and changing clinical practice by allowing a more fine-grained evaluation of treatment effects as well as by providing the opportunity for extending treatment beyond the clinical setting into real life with the development of ecological momentary interventions. Furthermore, this paper provides an overview of the technical details of setting up an ESM study in terms of design, questionnaire development and statistical approaches. Overall, although a number of considerations and challenges remain, ESM offers one of the best opportunities for personalized medicine in psychiatry, from both a research and a clinical perspective.

Daily-life stress differentially impacts ventral striatal dopaminergic modulation of reward processing in first-degree relatives of individuals with psychosis.

Emerging evidence shows that stress can impair the ability to learn from and pursue rewards, which in turn has been linked to motivational impairments characteristic of the psychotic disorder. Ventral striatal dopaminergic neurotransmission has been found to modulate reward processing, and appears to be disrupted by exposure to stress. We investigated the hypothesis that stress experienced in the everyday life has a blunting effect on reward-induced dopamine release in the ventral striatum of 16 individuals at a familial risk for psychosis compared to 16 matched control subjects. Six days of ecological momentary assessments quantified the amount of daily-life stress prior to [18F]fallypride PET imaging while performing a probabilistic reinforcement learning task. Relative to the controls, individuals at a familial risk for psychosis who encountered more daily-life stress showed significantly diminished extent of reward-induced dopamine release in the right ventral striatum, as well as poorer performance on the reward task. These findings provide the first neuromolecular evidence for stress-related deregulation of reward processing in familial predisposition to psychosis. The implication of daily-life stress in compromised modulation of reward function may facilitate the design of targeted neuropharmacological and ecological interventions.