# MAC/MAB–RCS: An Integrative Regulatory Control Framework for Risk Stratification and Personalized Intervention in Addiction Psychiatry

**Authors:** Anna Makarewicz, Remigiusz Recław, Anna Grzywacz, Jolanta Chmielowiec, Krzysztof Chmielowiec

PMC · DOI: 10.3390/brainsci16020187 · Brain Sciences · 2026-02-03

## TL;DR

This paper introduces a new framework for understanding and managing addiction by integrating biological and psychological factors to improve personalized treatment.

## Contribution

The MAC/MAB–RCS model offers a novel integrative framework for risk stratification and personalized intervention in addiction psychiatry.

## Key findings

- The Regulatory Control State (RCS) is a dynamic construct linking cognitive, emotional, and motivational processes in addiction.
- Disruption of the RCS is proposed as a transdiagnostic mechanism for craving and relapse across addictive behaviors.
- The model bridges neurobiological research and clinical practice, supporting precision psychiatry approaches.

## Abstract

Objectives: Addiction disorders remain a major challenge in contemporary psychiatry due to high relapse rates and significant individual and societal burden. Despite advances in addiction neurobiology, current diagnostic frameworks and dominant models offer limited tools for early risk identification and dynamic support of clinical decision-making across the course of treatment. The aim of this narrative review is to introduce the MAC/MAB–RCS model as an integrated conceptual framework for risk stratification and personalized intervention in addiction psychiatry. Methods: The proposed model integrates evidence from four complementary domains: genetic, epigenetic, and stress-axis biomarkers; functional brain network organization; and psychological/psychiatric dimensions relevant to addictive behaviors. These domains are synthesized into a unified conceptual structure designed to capture dynamic regulatory processes underlying addiction vulnerability. Results: At the core of the model lies the Regulatory Control State (RCS), a latent higher-order construct representing an individual’s dynamic regulatory capacity through the integration of cognitive control, emotional regulation, and motivational drive modulation. Disruption of the RCS is conceptualized as a shared transdiagnostic mechanism driving craving escalation, compulsive behavior, and relapse vulnerability, independent of substance class or specific addictive behavior. Conclusions: The MAC/MAB–RCS model aligns with the principles of precision psychiatry by offering a pragmatic, clinically oriented translational framework with potential applicability across clinical settings, bridging neurobiological research and clinical practice. The review discusses its relationship to existing models, potential clinical and systemic applications, key limitations, and priorities for future validation studies.

## Full-text entities

- **Genes:** FKBP5 (FKBP prolyl isomerase 5) [NCBI Gene 2289] {aka AIG6, FKBP51, FKBP54, P54, PPIase, Ptg-10}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}
- **Diseases:** injury to (MESH:D014947), Craving (MESH:C564883), Addiction disorders (MESH:D000437), Addiction (MESH:D019966), psychiatric (MESH:D001523), compulsive behaviors (MESH:D003193), impulsivity (MESH:D007174), RCS (MESH:C536209), emotional dysregulation (MESH:D021081)
- **Chemicals:** MAB (-), cortisol (MESH:D006854)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938299/full.md

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Source: https://tomesphere.com/paper/PMC12938299