Longitudinal stressor reactivity trajectories reveal risk profiles across early psychotic and affective disorders

Resilience to stress or adversity varies considerably across individuals, and understanding this variation is particularly relevant in psychosis risk, where identifying protective mechanisms could inform prevention. Stressor reactivity (SR), reflecting the degree of psychological change associated with exposure to stressful experiences, may help capture individual differences in vulnerability and adaptation over time. Therefore, examining longitudinal SR trajectories could reveal distinct resilience- and risk-related profiles with potential clinical relevance. Here, we aimed to identify different SR trajectories over 18 months and examine their predictors and functional consequences across healthy individuals and patients with early psychotic and affective disorders.

We computed SR based on clinical information from 460 healthy controls (HC), 285 patients with clinical high risk for psychosis (CHR), 293 patients with recent onset depression (ROD), and 296 patients with recent onset psychosis (ROP) of the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. Specifically, SR was computed as the difference between the expected and observed mental health response (P), as defined by the Beck Depression Inventory II (BDI-II), given the stressor exposure (E), as defined by the Cologne Life Events (CoLE), at baseline (T0), at 9-month follow-up (T1), and at 18-month follow-up (T2).

Latent class mixed models (LCMM) were used to identify SR trajectory classes, with study group, sex, age, and site as covariates. Between-class differences in childhood trauma (CTQ), depression (BDI-II), and life events (CoLE) were examined using Wilcoxon tests with Bonferroni correction, and linear mixed models were used to test whether depression changed differently over time between classes. Wilcoxon tests and ANCOVA examined whether class was associated with worse functional outcomes (GAF, FROGS) at T2, above and beyond baseline functioning and study group.

A stable low SR class (n = 1197, in which HC participants comprised the largest share, 37.4%) and an increasing SR class (n = 137, predominantly composed of clinical patients: CHR 33.6%, ROP 34.3%, ROD 23.4%) were identified, with class membership significantly associated with study group (p < .001). At baseline, the increasing SR class showed significantly higher depression (33.8 vs. 14.4), childhood trauma (43.7 vs. 36.4), and life events (8.06 vs. 6.41; all p < .01, effect sizes small to moderate). Depression diverged significantly over 18 months, with the stable low SR class improving markedly (14.4 to 5.51), while the increasing SR class remained persistently elevated (33.8 to 30.3; time × class interaction p < .001). The increasing SR class showed significantly worse symptom severity (57.1 vs. 76.6), disability (57.6 vs. 76.9), and overall functioning (66.0 vs. 77.7) at T2 (all p < .001, r = 0.29 to 0.36), with trajectory class predicting T2 functioning above and beyond baseline and study group (all p < .001, effect sizes small to moderate).

These findings suggest that a subgroup of predominantly clinical patients follows a persistently elevated and increasing SR trajectory, characterised by higher baseline vulnerability and associated with poorer functional outcomes at 18 months. Identifying individuals at risk for this trajectory early may inform targeted intervention and risk stratification across the psychosis spectrum.

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