The missing hallmark of health: psychosocial adaptation.

The eight biological hallmarks of health that we initially postulated (Cell. 2021 Jan 7;184(1):33-63) include features of spatial compartmentalization (integrity of barriers, containment of local perturbations), maintenance of homeostasis over time (recycling & turnover, integration of circuitries, rhythmic oscillations) and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, repair & regeneration). These hallmarks affect all eight somatic strata of the human body (molecules, organelles, cells, supracellular units, organs, organ systems, systemic circuitries and meta-organism). Here we postulate that mental and socioeconomic factors must be added to this 8×8 matrix as an additional hallmark of health ("psychosocial adaptation") and as an additional stratum ("psychosocial interactions"), hence building a 9×9 matrix. Potentially, perturbation of each of the somatic hallmarks and strata affects psychosocial factors and vice versa. Finally, we discuss the (patho)physiological bases of these interactions and their implications for mental health improvement.