Development of a theoretically-derived human anxiety syndrome biomarker

Abstract

Abstract“Anxiety disorders” are extremely common; and are a major source of health costs and lost work days. Their diagnosis is currently based on clinical symptom check lists and there are no biological markers to diagnose specific syndromal causes. This paper describes: 1) a detailed theory of the brain systems controlling anxiolytic-insensitive threat-avoidance and anxiolytic-sensitive threat-approach — where, in specific brain structures, activity generates specific normal behaviours, hyperactivity generates abnormal behaviours, and hyper-reactivity (hypersensitivity to input) generates specific clinical syndromes; 2) a rodent model of systemic anxiolytic action (rhythmical slow activity), linked to the theory, that over a period of 40 years has shown predictive validity with no false positives or false negatives — and which is likely to assay the sensitivity of endogenous systems that control anxiety; and, 3) derivation from this rodent-based theory of a specific non-invasive biomarker (goal-conflict-specific rhythmicity) for the threat-approach system in humans. This new biomarker should allow division of untreated “anxiety” patients, with superficially similar clusters of symptoms, into distinct high scoring (syndromal) and low scoring groups with different treatment-responses. This would be the first theoretically-derived biomarker for any mental disorder and should: 1) predict treatment efficacy better than current symptom-based diagnoses; 2) provide a human single dose test of novel anxiolytics; 3) provide a starting point for developing biomarkers for other “anxiety” syndromes; and so, 4) greatly improve treatment outcomes and cost-effectiveness.