ENZYMATIC LANDSCAPE OF ANXIETY DISORDERS: INTEGRATING GAD, MAO-A, HPA-AXIS ENZYMES, EPIGENETIC MODULATORS, CYP450 PATHWAYS AS DIAGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS

Abstract

According to current trends in Anxiety research anxiety is recognised as multi enzymatic pathological condition of upstream biosynthetic and regulatory dysfunctions rather than classical receptor-centric GABAergic models. This review proposes and elaborates an “Enzymatic Theory” of anxiety which describes the upstream enzymatic dysregulation as a primary mechanistic pathophysiology of anxiety. We examines and explains the role of Glutamic Acid Decarboxylase isoforms (GAD65/GAD67) in main inhibitory neurotransmitter Gama Aminobutyric Acid synthesis, Monoamine Oxidase-A (MAO-A) in serotonergic homeostasis, and 11β Hydroxysteroid Dehydrogenase (11β-HSD1/HSD2) in hypothalamic-pituitary-adrenal axis modulation as core anxiogenic and anxiolytic determinants and Epigenetic enzymes which including HDACs, DNMTs, and HATs, are reviewed as master chromatin regulators or DNA methylation modulators that encode stress-induced transcriptional silencing within fear circuits in brain which are responsible for anxiety. Furthermore, cytochrome P450 (CYP3A4, CYP2C19) and UDP-glucuronosyltransferase (UGT) systems are analysed as main enzymes responsible for anxiolytic drug pharmacokinetics and pharmacogenomic polymorphisms. Diagnostic enzyme panels include COMT Val158Met, MAO-A uVNTR, and CYP genotyping are evaluated as translational biomarkers for precision psychiatry. The integration of enzyme-responsive drug delivery, AAV-mediated GAD gene therapy, and epigenome-editing strategies will be the best move from symptom-based treatment to mechanistically biomarker-guided precise anxiolytic therapy.