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Antisocial personality disorder:Failure to balance excitation/inhibition?

Neuropharmacology

January 2025

Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany.

While healthy brain function relies on a dynamic but tightly regulated interaction between excitation (E) and inhibition (I), a spectrum of social cognition disorders, including antisocial behavior and antisocial personality disorder (ASPD), frequently ensuing from irregular neurodevelopment, may be associated with E/I imbalance and concomitant alterations in neural connectivity. Technological advances in the evaluation of structural and functional E/I balance proxies in clinical settings and in human cell culture models provide a general basis for identification of biomarkers providing a powerful concept for prevention and intervention across different dimensions of mental health and disease. In this perspective we outline a framework for research to characterize neurodevelopmental pathways to antisocial behavior and ASPD driven by (epi)genetic factors across life, and to identify molecular targets for preventing the detrimental effects of cognitive dysfunction and maladaptive social behavior, considering psychosocial experience; to validate signatures of E/I imbalance and altered myelination proxies as biomarkers of pathogenic neural circuitry mechanisms to determine etiological processes in the transition from mental health to antisocial behavior and ASPD and in the switch from prevention to treatment; to develop a neurobiologically-grounded integrative model of antisocial behavior and ASPD resultant of disrupted E/I balance, allowing to establish objective diagnoses and monitoring tools, to personalize prevention and therapeutic decisions, to predict treatment response, and thus counteract relapse; and finally, to promote transformation of dimensional disorder taxonomy and to enhance societal awareness and reception of the neurobiological basis of antisocial behavior and ASPD.

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