The “END” of Psychiatry: Epigenetic Neurochemical Dysregulation (END) as the Universal Mechanism and Framework for Psychopathology

DOI

No Doi

Published In

Year 2026 · Volume 1 · Issue 2

Published Online

May-August 2026

Pages

11-21

Article Type

Original Article

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The prevailing "chemical imbalance" theory of psychiatric disorders, attributing conditions to static neurotransmitter deficits or excesses, is fundamentally inadequate to explain core clinical phenomena such as treatment latency, symptom heterogeneity, and the profound impact of environmental factors. This paper introduces Epigenetic Neurochemical Dysregulation (END) as a universal framework proposing that psychopathology arises from dynamic, environmentally-sensitive epigenetic modifications orchestrating maladaptive alterations in neurochemical systems, synaptic plasticity, and neural circuit function. END integrates a comprehensive toolkit of interacting epigenetic mechanisms-spanning canonical DNA methylation (5mC) and its derivatives (5hmC), diverse histone post-translational modifications, chromatin remodeling complexes, extensive non-coding RNA regulation (miRNAs, lncRNAs), epigenetic control of RNA processing, and potentially protein-based prion-like mechanisms. By classifying major psychiatric disorders based on the nuanced upregulation or downregulation patterns across multiple neurotransmitter systems (dopamine, serotonin, glutamate, GABA, norepinephrine, acetylcholine, histamine, endocannabinoids, neuropeptides) driven by these epigenetic regulators, END provides a unified mechanistic understanding. This framework details how environmental exposures induce specific epigenetic changes leading to disorder phenotypes, reframes current therapeutics as epigenetic modulators, and illuminates pathways for developing targeted, mechanism-based diagnostics and potentially curative interventions, thereby heralding a necessary paradigm shift towards a more biologically informed Neopsychiatry.