Can the onset of major depression be predicted using physiological biomarkers? Critical transitions in the psycho-immune-neuroendocrine network

Background: Using a systems biology framework, the putative biological pathways underpinning major depressive disorder (MDD) can be viewed as belonging to a complex network. The psycho-immune-neuroendocrine (PINE) network is a physiological regulatory network, which comprises central nervous, immune, endocrine and autonomic systems, as well as the gut microbiome.
Objectives: The session aims to present testable hypotheses in relation to a change from health, through a pre-disease state, to a critical transition to MDD, as well as transitions in response to treatment.
Methods: The PINE network model has been constructed from physiological pathways described in the literature and the model, as well as hypotheses related to critical transitions in the PINE network, have been published.
Findings: Several interlaced regulatory negative feedback loops exist within the PINE network that become perturbed by chronic stress, potentially transitioning to positive feedback loops. It is hypothesized that feedback loop transitions can drive a critical transition of the entire PINE network from health into major depression. Putative physiological feedback loops are identified within hypothalamic–pituitary–adrenal and autonomic axes, the kynurenine pathway, gut function and the gut microbiome.
Conclusions: It is hypothesized that biomarkers that measure system instability can predict the critical transition from a pre-disease state to MDD. They may also be used to monitor treatment response in MDD. Examples of biomarkers are provided that may detect early warning signs of impending critical transitions within the PINE network. These markers may detect disease onset and may also provide measures of response to treatment.