Elevated emotion reactivity and emotion regulation in individuals at clinical high risk for developing psychosis and those diagnosed with a psychotic disorder.

AIMS: Disrupted affective processes are core features of psychosis; yet emotion reactivity and emotion regulation impairments have not been fully characterized in individuals at clinical high-risk for developing psychosis (CHR) or adolescents diagnosed with a psychotic disorder (AOP). Characterizing these impairments may provide a fuller understanding of factors contributing to psychosis risk and psychosis onset. Using cross-sectional and longitudinal data, we evaluated (1) group-level effects of emotion reactivity and regulation, (2) stability of group-level effects over time and age, (3) relationships between emotion reactivity and regulation, and (4) associations between these measures and psychosocial functioning and clinical symptomatology. METHODS: Eighty-seven participants (CHR = 32, TD = 42, AOP = 13; 12-25 years, 1-5 visits) completed the Emotion Reactivity Scale, Difficulties in Emotion Regulation Scale, and Emotion Regulation Questionnaire. We assessed psychotic symptoms with the Structured Interview for Prodromal Syndromes and measured real-world functioning with the Global Functioning: Social and Role Scales. We used analysis of variance to assess Aim 1 and linear mixed models to address Aims 2-4. RESULTS: CHR and AOP endorsed experiencing heightened levels of emotion reactivity and greater difficulty utilizing emotion regulation strategies compared to TD. These impairments were stable across time and adolescent development. Greater levels of emotion reactivity were associated with greater emotion regulation impairments. Greater impairments in emotion regulation were associated with lower social functioning and greater negative symptom severity. CONCLUSION: Therapeutic interventions designed to reduce emotion reactivity and improve one's ability to utilize emotion regulation strategies may be effective in reducing clinical symptomatology and improving real-world functioning in CHR and AOP.

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). Design, Setting, and Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Main Outcomes and Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). Conclusions and Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.