The Pedigree Is Not the Pathology: Familial Liability, Addiction-Associated Neuroadaptation and Behavioural Dysregulation in Medical Trainees

Behavioural dysregulation in medical trainees may coexist with familial vulnerability, substance exposure and altered neural function, yet their concurrence does not establish a common neuropathological cause. Familial aggregation cannot independently distinguish inherited liability from genetic nurture; molecular neuroadaptation cannot establish individual-level behavioural causation; and neuroimaging abnormalities are not equivalent to histopathological lesions. This critical narrative review examines these evidentiary boundaries and proposes FENCE-MED (Familial Liability, Exposure, Neuroadaptation, Circuit Concordance and Evidence-Based Intervention in Medical Education), a falsifiable framework for evaluating mechanistic attribution and clinical utility. Unlike integrative models describing genetic and neurobiological pathways of addiction, FENCE-MED specifies conditions under which familial, molecular and clinical findings may corroborate, contradict or fail to resolve a proposed causal mechanism. Its components include genetically informed family designs, substance-specific longitudinal exposure assessment, graded neuropathological evidence, an uncertainty-aware discordance matrix and prespecified causal and predictive validation. A prospective research architecture is outlined using independently assessed functional impairment, repeated psychiatric phenotyping, selected mechanistic substudies and external validation. The corresponding clinical pathway prioritises confidential assessment, established addiction treatments and demonstrable functional recovery without employing genetic or molecular findings for educational or disciplinary classification. FENCE-MED is neither a diagnostic instrument nor an established preventive intervention. Its proposed contribution is an explicit, testable boundary between inherited susceptibility, addiction-associated neural change, causal explanation and clinically justified action.