Beyond the brain circuit: a biopsychosocial integrative review of addiction neuroscience, epigenetic mechanisms, and multidisciplinary treatment
TL;DR
A central argument of this review is that addiction is not solely a brain circuit disorder but also a disorder of social connection and meaning, in which neuromodulation serves as one component of a comprehensive approach that targets the neurobiological, psychological, and relational dimensions of addiction simultaneously.
Abstract
This integrative review examines the neurobiological basis of addiction and neuromodulation-based treatment approaches in light of current literature, while proposing an integrative framework that extends beyond purely biological explanations. The neuroscience of addiction is addressed within Koob and Volkow’s three-stage neurocircuit model (binge/intoxication, withdrawal/negative affect, and preoccupation/craving), encompassing neuroadaptations in reward, stress, and executive control circuits, neuroimaging findings, genetic and epigenetic mechanisms, and neuromodulation-based treatment approaches. A central argument of this review is that addiction is not solely a brain circuit disorder but also a disorder of social connection and meaning: trauma, early adversity, insecure attachment, and social isolation constitute both neurobiological triggers and perpetuating factors of addiction, leaving epigenetic traces on reward and stress circuits that interact with genetic vulnerability. Genome-wide association studies emphasize polygenic risk architecture, while epigenetic mechanisms — particularly DNA methylation and histone modifications — translate environmental exposures into lasting neuroadaptations. Critically, the distinction between state and trait epigenetics must be carefully considered when interpreting cross-sectional findings, as longitudinal designs are required to establish translational clinical validity. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have demonstrated promising results in reducing craving and relapse risk; however, clinical application requires careful patient selection, standardized multi-session protocols, and integration with pharmacotherapy and psychotherapy. This review proposes a three-layer multidisciplinary treatment framework — biological, psychological, and social-relational — in which neuromodulation serves as one component of a comprehensive approach that targets the neurobiological, psychological, and relational dimensions of addiction simultaneously.