Early warning biomarkers in major depressive disorder: a strategic approach to a testing question

Purpose: Identification of biomarkers in major depressive disorder (MDD) has proceeded in an extemporised manner. No single biomarker has been identified with utility in screening, diagnosis, prognosis, or monitoring, and screening tests have different characteristics than the other functions. Using chaos, bifurcation, and perturbation (CBP) theories, the aim is to identify biomarkers to aid clinicians in screening for MDD.

Materials and methods: MDD is a complex disorder; consequently, a reductionist approach to characterize the complex system changes found in MDD will be inchoate and unreliable. A holistic approach is used to identify biomarkers reflecting the tipping points seen before the catastrophic bifurcation that results in MDD.

Results: Applying CBP theories revealed skew, resistance to change, flickering, increased variance and autocorrelation as patterns of biomarkers. Integrals and differentials of extracellular and intracellular biomarkers were identified, specifically focussed on hypothalamo-pituitary axis (HPA) dysfunction, metabolic dysfunction, inflammation and mitochondrial oxidative stress, and tryptophan metabolism.

Conclusions: Applying CBP theories to the dysfunctional complex biological systems in MDD led to development of integrals and differentials of biomarkers that can be used in screening for MDD and planning future biomarker research, targeting intracellular and extracellular inflammation, HPA axis dysfunction, and tryptophan metabolism.