The Investing Fascia–Carotid Sheath–Six-System Coupling Hypothesis: A New Framework for the Cervicogenic Mechanical Pathogenesis of Anxiety Disorders and Depression

Classical pathogenetic mechanisms of anxiety disorders and depression involve monoamine neurotransmitter imbalance, hypothalamic–pituitary–adrenal (HPA) axis hyperactivation, neuroinflammation, decreased neuroplasticity, gamma-aminobutyric acid (GABA)/glutamate excitatory–inhibitory imbalance, gut–brain axis disturbance, circadian rhythm disruption, epigenetic programming, mitochondrial dysfunction, and glial network abnormalities. However, these mechanisms mainly explain how mood disorders are maintained and amplified in the body, and they still lack a unified framework for upstream triggers and patient heterogeneity. This article proposes the “Investing Fascia–Carotid Sheath–Six-System Coupling Hypothesis.” The hypothesis posits that chronic forward head posture, long-term stress, aging, and chronic low-grade inflammation synergistically drive fibrosis of the posterior investing fascia; after the investing fascia loses elastic buffering, abnormal shear stress generated by daily head and neck micromovements is transmitted through the three-layer deep cervical fascia network to the carotid sheath; elevated intrasheath pressure serves as an inferred common physical signal that synchronously affects six systems: arterial, venous, lymphatic, glymphatic, sympathetic, and vagal; abnormalities in the six systems drive anxiety, depression, and their comorbid symptoms through nucleus of the solitary tract–locus coeruleus–norepinephrine (NTS-LC-NE) pathways, the HPA axis, GABA/glutamate, monoamine, brain-derived neurotrophic factor (BDNF)/mammalian target of rapamycin (mTOR), and neuroinflammatory networks; the six systems mutually amplify through positive feedback loops, forming a vicious cycle of “mechanical abnormality → six-system dysfunction → mood disorder → worsening posture → aggravated mechanical abnormality.” This hypothesis applies to unipolar depression and anxiety patients of the cervicogenic mechanical subtype, is not intended to apply to all patients, and does not replace classical theories. Bipolar depression is not fully consistent with this hypothesis: glymphatic impairment is a shared feature of major depressive disorder (MDD) and bipolar disorder (BD) (Fu et al., 2026), but there is currently no direct evidence as to whether investing fascia mechanical coupling is an upstream trigger of bipolar depression. This article proposes testable predictions and a three-stage validation framework, and all evidence is strictly limited to the 66 core references included in this article.