Brain-based gene expression and corresponding behavioural relevance of risk genes for broad antisocial behaviour

Jaroslav Rokicki; Megan L Campbell; Dennis van der Meer; Alina I Sartorius; Natalia Tesli; Piotr Jahołkowski; Alexey Shadrin; Ole Andreassen; Lars T Westlye; Daniel S Quintana; Unn K Haukvik

doi:10.1016/j.neuroimage.2025.121198

Brain-based gene expression and corresponding behavioural relevance of risk genes for broad antisocial behaviour

Neuroimage. 2025 May 1:311:121198. doi: 10.1016/j.neuroimage.2025.121198. Epub 2025 Apr 10.

Authors

Affiliations

¹ Centre of Research and Education in Forensic Psychiatry (SIFER), Oslo University Hospital, Oslo, Norway. Electronic address: jaroslav.rokicki@ous-research.no.
² SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Global Initiative for Neuropsychiatric Genetics Education in Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, , Netherlands.
⁴ Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
⁵ Centre of Research and Education in Forensic Psychiatry (SIFER), Oslo University Hospital, Oslo, Norway; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶ Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway.
⁸ Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; NevSom, Department of Rare Disorders and Disabilities, Oslo University Hospital, Oslo, Norway.
⁹ Centre of Research and Education in Forensic Psychiatry (SIFER), Oslo University Hospital, Oslo, Norway; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Mental health and addiction, Institute of Clinical Medicine, University of Oslo, Norway.

PMID: 40216214
DOI: 10.1016/j.neuroimage.2025.121198

Abstract

Antisocial behaviour (ASB) involves persistent irresponsible, delinquent activities violating rights and safety of others. A meta-analysis of genome-wide association studies revealed significant genetic associations with ASB, yet their brain expression patterns and behavioural relevance remain unclear. Our investigation of fifteen genes associated with ASB examined their biological role and distribution across tissues, integrating post-mortem brain sample data from the Allen-Human-Brain Atlas and the Genotype-Tissue Expression project. We found that these genes were differentially expressed in the brain, particularly in regions like the cerebellum, putamen, and caudate, and were notably downregulated in the pancreas. Single cell type expression analysis revealed that ASB-associated genes had strong correlations with ductal and endothelial cells in the pancreas, indicating a possible metabolic influence on ASB. Certain genes like NTN1, SMAD5, NCAM2, and CDC42EP3 displayed specificity for cognitive terms including chronic pain, heart rate, and aphasia. These expression patterns aligned with neurocognitive domains related to thinking, and learning, distress, motor skills, as determined by fMRI analysis. This study connects specific brain gene expression with potential genetic and metabolic factors in ASB, offering novel insights into its biological basis and possible interdisciplinary approaches to understanding and addressing aggressive behaviours.

Keywords: Antisocial behaviour; Gene expression; Neurocognitive correlates; fMRI meta-analysis.

MeSH terms

Adult
Antisocial Personality Disorder* / genetics
Antisocial Personality Disorder* / metabolism
Brain* / metabolism
Female
Gene Expression*
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Magnetic Resonance Imaging
Male
Middle Aged