The Neuro-Hepatic-Affective Model (NHAM): A Systems Framework for Liver–Brain Modulation of Emotion in Precision Psychiatry

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Abstract

Background — Emotional regulation has traditionally been modelled within cortico-limbic circuits, yet converging evidence shows that the liver–brain axis continuously modulates affective dynamics through metabolic–endocrine, inflammatory–immune, microbiota–vagal, and autonomic pathways. The absence of a unified quantitative framework linking hepatic biology to parameterized affective oscillations limits early detection, mechanistic diagnosis, and personalized interventions in psychiatry. Methods — We introduce the Neuro-Hepatic-Affective Model (NHAM), which formalizes mood as a latent affective oscillator: E(t) = B₀ + A · e^{(-t/τ)} · sin(ω t) where A = reactivity, B₀ = tonic baseline, ω = recovery tempo, and τ = persistence. Multi-omic and psychophysiological biomarkers are mapped to pathway-specific parameter shifts: bile acids & FGF19 → metabolic–endocrine; CRP, IL-6, kynurenine/tryptophan ratio → inflammatory–immune; microbial diversity & short-chain fatty acids → microbiota–vagal; heart rate variability (HRV) → autonomic regulation. Biomarker–parameter mappings were derived from meta-analyses, randomized controlled trials, and longitudinal studies. Results — Distinct biomarker profiles yield reproducible parameter shifts. Elevated IL-6 predicts ↑B₀ and ↓ω; high bile acids (FXR–TGR5/FGF19) predict ↓A, ↑ω, ↓τ; higher microbial diversity / HF-HRV predict ↓A, ↓B₀, ↑ω, ↓τ. This mapping enables pathway-specific diagnostics and quantitative tracking of affective dynamics. Conclusions — NHAM is the first systems biology framework to integrate liver–brain pathways into a parameterized model of emotion. By linking multi-omic biomarkers to latent affective dynamics, NHAM offers a foundation for precision psychiatry — enabling real-time monitoring, mechanistic diagnosis, and targeted interventions. Future work should combine wearable biosensors, laboratory assays, and ecological momentary assessment to validate NHAM in clinical populations and develop closed-loop therapeutic systems.

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