2026 ECNP Congress

PS03-3240

Morphometric signatures of schizotypal traits and clinical psychosis: 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

Exposure to adverse childhood experiences (ACEs) is a pervasive risk factor for psychosis, exhibiting a linear relationship across the spectrum from subclinical schizotypy to schizophrenia spectrum disorders (SSDs). Traditionally, this is conceptualised within a vulnerability–stress framework[1] where early-life adversity reconfigures neural circuits supporting cognitive and emotional regulation[2]. However, the relationship between trauma, brain structure, and phenomenology is poorly understood and it remains a matter of debate whether structural alterations are the primary mechanistic vehicle for trauma-induced schizotypy or if they represent an independent, non-redundant risk pillar[3]. Addressing this ambiguity, our aim was to quantify the unique and shared contributions of childhood adversity and regional brain morphometry to the expression of schizotypal traits across the psychosis spectrum.

We examined structural magnetic resonance imaging (MRI) data from a matched sample of 120 individuals (aged 17–39). The cohort comprised three groups: 40 patients with a first-episode SSD, 40 healthy individuals with high schizotypal traits (HS), and 40 with low schizotypy (LS). Schizotypy was quantified using the Multidimensional Schizotypy Scale (MSS) and the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), while ACEs were assessed via the Childhood Trauma Questionnaire (CTQ). Cortical thickness and subcortical volumes were extracted via surface-based morphometry from high-resolution T1-weighted scans. Following the identification of regional neuroanatomical differences via FDR-corrected ANCOVAs, we utilised multinomial logistic regression to define phenotypic predictors. Finally, a comprehensive variance partitioning analysis (Commonality analysis) was conducted to quantify the unique and shared variance in total schizotypal symptoms (MSS and O-LIFE) explained by trauma severity and structural region signature.

ACE prevalence increased significantly across the spectrum (LS: 32.5% < HS: 65% < SSD: 87.5%; p<0.001). Morphometric alterations were concentrated in a limbic–temporal–frontal network, with the right posterior cingulate cortex (rPCC) and left caudal anterior cingulate cortex (left cACC) emerging as the most robust indicators of clinical severity. Regression analysis identified a divergent signature in the right inferior temporal gyrus (rITG): increased thickness was associated with the HS phenotype, suggesting a state of compensatory hypertrophy, whereas reduced thickness was characteristic of the SSD group[4].

Variance partitioning confirmed that ACEs and regional morphometry contribute to the phenotype via parallel pathways. Childhood trauma accounted for 28.3% to 33.9% of unique variance in symptoms (for MSS and OLIFE, respectively), while the 13-region neuroanatomical signature provided a significant, independent contribution of 10.8% to 11.1%. Crucially, the shared variance between trauma and brain structure was minimal (~1.5%), with the models explaining 40.9% to 46.1% of the spectrum’s variance beyond demographic baselines. These findings provide evidence for structural–phenomenological decoupling across the psychosis spectrum. Early-life adversity and neuroanatomical reconfiguration seem to represent independent risk pillars: while ACEs act as the primary engine of schizotypal phenomenology, structural markers such as the rPCC and left cACC represent a separate, non-redundant biological diathesis. The divergent role of the rITG suggests a neurobiological “tipping point” where compensatory mechanisms in subclinical states go into atrophy during clinical transition. Clinically, this suggests that trauma-informed care and neuroprotective strategies must be viewed as parallel therapeutic targets.

References

  1. Rudnick A, Lundberg E. The stress-vulnerability model of schizophrenia: A conceptual analysis and selective review. Curr Psychiatry Rev. 2012;8(4):337-341. doi:10.2174/157340012803520450
  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. Thomason ME, Marusak HA. Toward understanding the impact of trauma on the early developing human brain. Neuroscience. 2017;342:55-67. doi:10.1016/j.neuroscience.2016.02.022
  4. Omlor W, Rabe F, Fuchs S, et al. Estimating Multimodal Structural Brain Variability in Schizophrenia Spectrum Disorders: A Worldwide ENIGMA Study. Am J Psychiatry. 2025;182(4):373-388. doi:10.1176/appi.ajp.20230806