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Authors: H.-L ×
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01.
medRxiv (Medicine) 2026-06-17

Adverse Childhood Experiences Reorganise the Brain-Personality Network Across the Psychosis Spectrum

Exposure to adverse childhood experiences is a pervasive risk factor for psychosis, exhibiting a linear relationship across the psychosis spectrum from subclinical schizotypal traits to schizophrenia spectrum disorders. While this association is often conceptualised within the vulnerability-stress framework, the systemic mechanisms through which childhood trauma reconfigures the brain-personality interactome remain poorly understood. We examined clinical, neuropsychological, and neuroimaging data from a sample of low- and high-schizotypy individuals, and patients with a diagnosis of schizophrenia spectrum disorder (N=120). Our aim was to map how trauma reconfigures interactions between neurobiology and schizotypal phenomenology. We adopted a mixed graphical model approach to jointly estimate conditional dependencies between childhood trauma, regional brain morphometry, and schizotypal traits across the psychosis spectrum. Our results show that childhood trauma reconfigures the brain-personality network, shifting it from a state driven by cognitive processes to one anchored in emotional (limbic) reactivity. This transition is marked by the increased influence of impulsive traits and a significant strengthening of connections within the salience network. These changes converge with a reduced thickness of the frontal executive regions, the brain's control centres, identified in our models. Collectively, our results suggest a structural phenomenological decoupling, where trauma conditioned affective circuits may bypass weakened top-down regulatory controls. These findings highlight the necessity of using integrative frameworks to capture how trauma fundamentally reshapes the relationship between the brain and schizotypal personality.

02.
medRxiv (Medicine) 2026-06-15

CDH13 is associated with cellular viability after exposure to ionizing radiation using genome-wide screening

Background: It is well known that genetic variants contribute to cellular sensitivity to chemotherapeutic agents and ionizing radiation (IR). The aim of this study was to identify single nucleotide polymorphisms (SNPs) and genes associated with the spectrum of normal cellular sensitivity of lymphoblastoid cell lines (LCLs) towards ionizing radiation and mitomycin C (MMC). Methods: In a first step, we determined the viability of LCLs established from male participants of the Berlin Aging Study II (BASE-II) aged >=62 years following treatments with increasing doses of IR (n=137 cell lines) or MMC (n=140 cell lines) using the alamarBlue assay. Results from intra-experimental triplicates and three independent experiments for each cell line and treatment were used to calculate the area under the curves (AUCs) representing the specific sensitivity to IR and MMC of each LCL. The data from these experiments were subsequently used as outcomes in genome-wide association studies (GWASs). In addition, we calculated polygenic risk scores (PGS) from UK Biobank GWAS results for four cancer-related phenotypes and assessed the extent to which the variance in the IR and MMC sensitivity is explained by these PGS. Results: The GWAS analyses revealed one variant, rs74728080, located in CDH13 on chromosome 16, to show genome-wide significant (p < 5 x 10-8, beta = 2.81) association with cellular viability after treatment with IR. In the GWAS on MMC sensitivity the most interesting signal was elicited by SNP rs113978558 in an intron of the PLD5 gene on chromosome 1 (p = 9.232 x 10-8; beta = 1.44). Several other SNPs with statistically suggestive (i.e., p < 1 x 10-5) evidence of association with IR or MMC sensitivity were identified. PGSs calculations from GWAS of four cancer-related traits in UKB explained ~5% and ~3% of phenotypic variance in IR- and MMC-induced cell viability, respectively. Conclusion: The genome-wide significant association of rs74728080 with IR sensitivity and the location of this variant in CDH13 is interesting and functionally highly plausible given its known involvement in oxidative-stress response and function as tumor suppressor. Taken together, our novel data suggest that CDH13 may be genuinely involved in regulating cellular IR sensitivity.