Individual-level deviations from normative brain morphology in violence, psychosis, and psychopathy

Background Neuroimaging research has shown brain morphological abnormalities associated with violence and psychosis, but individual differences are substantial and results not consistent across studies. Recently developed normative modeling of brain MRI-features provides a possibility to parse this heterogeneity by mapping inter-individual brain characteristics, which has not yet been explored in forensic psychiatry. Methods We explored brain heterogeneity in persons with a history of severe violence with or without a schizophrenia spectrum disorder (HoV, n=58), non-violent patients with schizophrenia spectrum disorders (SSD-NV, n=138), and healthy non-violent controls (HC) from lifetime normative trajectories of cortical thickness, surface area, and subcortical volumes. Normative models were based on Freesurfer derived regions of interest from 58,836 individuals (ages 2-100) from 82 sites. Group differences and associations between brain deviations and psychopathy traits (PCL-R scores) were investigated. Results Across groups, we found an overall heterogeneous pattern of individual-level deviations, with a significantly higher frequency of extreme negative deviations in HoV ( p =.020, d =.31) and SSD-NV ( p =.019, d= . 48) , than HC. Group differences were mostly present in subcortical volumes and cortical area, but not thickness, with significant regional group-level differences within the subcallosal and insular cortices, and the cerebellum, and no significant associations to psychopathy traits. Conclusion By applying normative modeling, this proof-of-concept study demonstrates the heterogeneous pattern of brain morphometry deviations associated with violence and psychosis. While the results warrant replication, studies addressing individual brain deviations may contribute to improved understanding of the complex underpinnings of violence in forensic psychiatry. ### Competing Interest Statement OAA has received a speaker honorarium from Lundbeck and Janssen and is a consultant to cortechs.ai. IA has received a speaker honorarium from Lundbeck. All the other authors report no conflicts of interest. ### Funding Statement This work was supported by The Research Council of Norway (OAA, #223273), and South-Eastern Norway Health Authorities (UKH, #2016044; UKH, #2019117; UKH, #2020100; OAA, #2017112). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Norwegian Regional Committee for Medical Research Ethics approved the project (REK Sor Ost C 2017/482) which was conducted in accordance with the Helsinki declaration. All participants submitted written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors