Polygenic risk, familial liability and stress reactivity in psychosis: an experience sampling study

Background There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls. Methods We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS. Results We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWE<0.001). In contrast to our hypotheses, siblings with high PRS reported less intense psychotic experiences in response to momentary stress compared to siblings with low PRS. No differences in magnitude of these associations were observed in cases with high v. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS. Conclusions This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

The rosy future paradox: Positive future thinking without task relevance enhances negative biases and anxiety for aversive events

Expectations have an important role in guiding behavior and the interpretation of novel information, but can contain negative biases such as is the case in anxiety disorders. Positive future thinking may provide an accessible way to attenuate these negatively biases. However, much is still unclear about the optimal form of such positive interventions, and it is unknown if the effects go beyond subjective experience. Here, we used a positive future thinking intervention to adapt the way a stressful event is experienced. Participants imagined either task-relevant (N = 21) or irrelevant (N = 21) positive future events before being subjected to the Trier Social Stress Task, or did not receive the intervention (N= 20). We recorded resting state EEG during the anticipation and recovery phases of the TSST to assess intervention and trait anxiety related differences in the level of frontal delta-beta coupling, which is considered a neurobiological substrate of emotion regulation. Results show that the intervention reduces event-related stress and anxiety, and increases social fixation behavior and task performance, but only if future thinking is task relevant. Paradoxically, task-irrelevant positive future thoughts enhance negative perceptual biases and stress reactivity. This increase in stress reactivity in the task-irrelevant group was corroborated by the elevated levels frontal delta-beta coupling during event anticipation, especially for those with high trait anxiety. This suggests an increased demand for emotion regulation following the task-irrelevant intervention, possibly due to the contextual incongruence between positive imagery and the stressor. Together, these results show that positive future thinking can mitigate the negative emotional, behavioral and neurobiological consequences of a stressful event, but that it should not be applied indiscriminately. Task-relevant positive future thinking can be an accessible way to boost efficacy of exposure therapy for pathological anxiety, and can help people deal with negative anticipation in daily life.

Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

Genetic predisposition and environmental stress are known etiologies of stress-related psychiatric disorders. Environmental stress during adolescence is assumed to be particularly detrimental for adult affective behaviors. To investigate how genetic stress-reactivity differences modify the effects of stress during adolescence on adult affective behaviors we employed two inbred strains with differing stress reactivity. The Wistar Kyoto More Immobile (WMI) rat strain show increased stress-reactivity and despair-like behaviors as well as passive coping compared to the nearly isogenic control strain, the Wistar Kyoto Less Immobile (WLI). Males and females of these strains were exposed to contextual fear conditioning (CFC) during early adolescence (EA), between 32 and 34 postnatal days (PND), and were tested for the consequences of this mild EA stress in adulthood. Early adolescent stress significantly decreased anxiety-like behavior, measured in the open field test (OFT) and increased social interaction and recognition in adult males of both strains compared to controls. In contrast, no significant effects of EA stress were observed in adult females in these behaviors. Both males and females of the genetically less stress-reactive WLI strain showed significantly increased immobility in the forced swim test (FST) after EA stress compared to controls. In contrast, immobility was significantly attenuated by EA stress in adult WMI females compared to controls. Transcriptomic changes of the glucocorticoid receptor (Nr3c1, GR) and the brain-derived neurotrophic factor (Bdnf) illuminate primarily strain and stress-dependent changes, respectively, in the prefrontal cortex and hippocampus of adults. These results suggest that contrary to expectations, limited adolescent stress is beneficial to males thru decreasing anxiety and enhancing social behaviors, and to the stress more-reactive WMI females by way of decreasing passive coping.

Effects of a Novel, Transdiagnostic, Hybrid Ecological Momentary Intervention for Improving Resilience in Youth (EMIcompass): Protocol for an Exploratory Randomized Controlled Trial

Background Most mental disorders first emerge in youth and, in their early stages, surface as subthreshold expressions of symptoms comprising a transdiagnostic phenotype of psychosis, mania, depression, and anxiety. Elevated stress reactivity is one of the most widely studied mechanisms underlying psychotic and affective mental health problems. Thus, targeting stress reactivity in youth is a promising indicated and translational preventive strategy for adverse mental health outcomes that could develop later in life and for improving resilience. Compassion-focused interventions offer a wide range of innovative therapeutic techniques that are particularly amenable to being implemented as ecological momentary interventions (EMIs), a specific type of mobile health intervention, to enable youth to access interventions in a given moment and context in daily life. This approach may bridge the current gap in youth mental health care. Objective This study aims to investigate the clinical feasibility, candidate underlying mechanisms, and initial signals of the efficacy of a novel, transdiagnostic, hybrid EMI for improving resilience to stress in youth—EMIcompass. Methods In an exploratory randomized controlled trial, youth aged between 14 and 25 years with current distress, a broad Clinical High At-Risk Mental State, or the first episode of a severe mental disorder will be randomly allocated to the EMIcompass intervention (ie, EMI plus face-to-face training sessions) in addition to treatment as usual or a control condition of treatment as usual only. Primary (stress reactivity) and secondary candidate mechanisms (resilience, interpersonal sensitivity, threat anticipation, negative affective appraisals, and momentary physiological markers of stress reactivity), as well as primary (psychological distress) and secondary outcomes (primary psychiatric symptoms and general psychopathology), will be assessed at baseline, postintervention, and at the 4-week follow-up. Results The first enrollment was in August 2019, and as of May 2021, enrollment and randomization was completed (N=92). We expect data collection to be completed by August 2021. Conclusions This study is the first to establish feasibility, evidence on underlying mechanisms, and preliminary signals of the efficacy of a compassion-focused EMI in youth. If successful, a confirmatory randomized controlled trial will be warranted. Overall, our approach has the potential to significantly advance preventive interventions in youth mental health provision. Trial Registration German Clinical Trials Register DRKS00017265; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017265 International Registered Report Identifier (IRRID) DERR1-10.2196/27462

Temporal Patterns of Daily Behavioral and Psychological Symptoms of Dementia Throughout the Day

Behavioral and psychological symptoms of dementia (BPSD) are taxing for both the person with dementia (PWD) and their family caregivers. Yet, little is known about how BPSD fluctuates throughout the day (i.e., morning, daytime, evening, and night; e.g., sundowning) and how caregivers perceive BPSD at different times of the day. Using 8-day daily diary data from 173 family caregivers whose relatives were using Adult Day Services (ADS), this study investigated temporal patterns of BPSD and caregivers’ stress responses to BPSD throughout the day. Overall, the number of BPSD was highest in the evening, and caregivers’ stress reactivity to BPSD increased throughout the phases of the day (i.e., most stressful at night). However, caregivers showed lower reactivity to BPSD in the mornings and at night on days when the PWD used ADS. Our findings about fluctuations of (caregiver reactions to) BPSD throughout the day suggest target windows for just-in-time adaptive intervention.