Anxiety as persistent alarm: State-of-the-art mechanisms, treatment gaps, and a coherence-based measurement proposal (CAMERS2/Spirit Index)

Anxiety disorders are the most prevalent class of mental disorders worldwide, affecting approximately 4.4% of the global population (≈359 million individuals in 2021), with substantial treatment gaps across settings (WHO Mental Health Atlas 2020). Contemporary neuroscience conceptualizes anxiety as the maladaptive persistence of defensive “alarm” states driven by altered threat learning, interoceptive amplification, and autonomic inflexibility rather than solely excessive conscious fear. Despite advances in mechanistic understanding and effective first-line treatments, clinical assessment remains largely symptom-aggregative, often obscuring heterogeneity in sustaining processes and limiting personalization. This state-of-the-art review synthesizes current evidence on epidemiology, neurobiological mechanisms, autonomic regulation, psychophysiological markers, and evidence-based interventions. It identifies persistent gaps in multidomain assessment, particularly in localizing where vigilance persists across cognitive, emotional, behavioral, relational, and existential domains. A coherence-based framework (CAMERS 2 /Spirit Index) is presented as an emerging multidomain assessment model designed to distinguish severity from pattern and to map potential sites of misalignment. At present, CAMERS 2 /Spirit Index should be interpreted as a conceptual and hypothesis-generating proposal rather than as a validated clinical instrument. No peer-reviewed psychometric, clinical-outcome, or biomarker validation study of CAMERS 2 /Spirit Index has yet been published; therefore, its domains, coherence scores, disruption flags, and rhythm-type labels should not be used for diagnosis, treatment selection, or biologically informed phenotyping outside research contexts. Rather than replacing established diagnostic systems, this model is discussed as a hypothesis-generating complement requiring independent validation. Future work should evaluate psychometric robustness, incremental validity over established scales, predictive utility for treatment response, pragmatic clinical integration, and ethical safeguards. Advancing precision in anxiety care may depend not only on suppressing symptoms, but on clarifying the domains in which vigilance remains unresolved.