2026 ECNP Congress

PS03-3040

Reconfiguring the brain-personality interactome across the psychosis spectrum: the role of early life adversity

Pierfrancesco Sarti — G. Cecere, W. Omlor, J.M.C. Blom, P. Homan · University of Zurich, Department of Adult Psychiatry and Psychotherapy, Zurich, Switzerland

2026 ECNP Congress

Adverse childhood experiences (ACEs) are among the most potent environmental risk factors for psychotic phenomena, exhibiting a relationship that extends from subclinical schizotypal personality traits to schizophrenia spectrum disorders (SSD)[1]. ACEs occurs during sensitive neurodevelopmental windows, potentially acting as a biological disruptor that reconfigures neural circuits supporting executive control and emotion regulation[2]. While neuroimaging has identified structural alterations associated with trauma, the systemic mechanisms through which childhood adversity reconfigures the “interactome” (the complex dependencies between brain morphology and schizotypal personality) remain poorly understood. Network theory offers a compelling framework to evaluate how trauma-related reorganisation may lead to enduring changes in the global architecture of these associations[3,4]. Our aim was to understand if and how childhood trauma acts as a systemic moderator that rewires the dependencies between brain morphometry and schizotypal phenomenology across the psychosis spectrum.

The sample (N=120) comprised three age- and education-matched groups: 40 patients with SSD, 40 individuals with high schizotypal personality traits (HS) and 40 with low schizotypy (LS). Schizotypal personality traits were evaluated using the Multidimensional schizotypy scale (MSS) and the Oxford-Liverpool inventory of feelings and experiences (O-LIFE). Cortical thickness and subcortical volumes were extracted via surface-based morphometry from high-resolution T1-weighted MRI scans. We utilised a mixed graphical model with L1 LASSO regularisation to estimate the comprehensive network of conditional dependencies[5]. Childhood trauma questionnaire total scores were integrated as a categorical moderator using the scale’s cut-off of 35. Global and edge-specific network reconfigurations were evaluated using the Network Comparison Test (NCT) with 1,000 permutations. Centrality metrics and node-wise predictability (R2) were also calculated and their stability was tested.

Childhood trauma fundamentally reorganised the brain-personality network. The trauma group exhibited significantly higher network density (37.36%) compared to the no-trauma group (15.38%; p=0.03), with formal testing confirming a significant difference in global architecture (p=0.03). Structurally, trauma reconfigured the covariance between the anterior cingulate (left rACC and left cACC; p=0.03) and strengthened the link between the rACC and the right insula (p=0.01), alongside alterations in the inter-hemispheric connection of the default mode network (bilateral posterior cingulate; p=0.04).

When incorporating personality dimensions, schizotypy in individuals with no history of ACEs was primarily defined by cognitive–perceptual traits, with MSS positive acting as the most influential node. Under the ACE condition, MSS positive influence decreased while the impulsive nonconformity (O-LIFE) scale showed a tripling of relative influence and an increase in predictability (from R2=0.31 to 0.73). This component, along with introvertive anhedonia, revealed significantly altered edge invariance with the amygdala (p=0.006). Furthermore, trauma reconfigured the specific relationships between MSS positive traits and both the rACC (p=0.013) and right amygdala (p=0.046).

Our findings show that early adversity acts as a systemic catalyst, triggering an affective-cognitive decoupling. In trauma-exposed individuals, personality traits appear hard-wired into primary affective centres rather than being governed by stable cortical scaffolding. Such structural–phenomenological decoupling, where thinned prefrontal regions seem to fail to modulate stress-sensitive salience circuits, may explain the higher stress reactivity and diverse clinical trajectories observed across the psychosis spectrum.

References

  1. Toutountzidis D, Gale TM, Irvine K, Sharma S, Laws KR. Childhood trauma and schizotypy in non-clinical samples: A systematic review and meta-analysis. PloS One. 2022;17(6):e0270494. doi:10.1371/journal.pone.0270494
  2. Quidé Y, Watkeys OJ, Tonini E, et al. Childhood trauma moderates schizotypy-related brain morphology: Analyses of 1182 healthy individuals from the ENIGMA schizotypy working group. Psychol Med. 2024;54(6):1215-1227. doi:10.1017/S0033291723003045
  3. Golay P, Chevrot A, Conus P, Fagiolini A, Malla AK, Merlo MC. Pathways between childhood trauma, clinical symptoms and functioning in first-episode psychosis: A network analysis. NPJ Schizophr. 2025:11.
  4. Huang Y hang, Hu H xin, Wang L ling, et al. Relationships between childhood trauma and dimensional schizotypy: A network analysis and replication. Asian J Psychiatry. 2023;85:103598. doi:10.1016/j.ajp.2023.103598
  5. Haslbeck JMB, Waldorp LJ. mgm: Estimating Time-Varying Mixed Graphical Models in High-Dimensional Data. J Stat Softw. 2020;93:1-46. doi:10.18637/jss.v093.i08