N J C Stapelberg1, R Pratt2, D L Neumann3, D H K Shum4, S Brandis5, V Muthukkumarasamy6, B Stantic7, M Blumenstein8, J P Headrick9. 1. Bond University Faculty of Health Sciences and Medicine and Gold Coast Hospital and Health Services, 14 University Dr, Robina, Queensland 4226, Australia. Electronic address: cstapelb@bond.edu.au. 2. Gold Coast University Hospital, Gold Coast, QLD, Australia. Electronic address: robin.pratt@health.nsw.gov.au. 3. School of Applied Psychology, Griffith University, Gold Coast, QLD, Australia. Electronic address: d.neumann@griffith.edu.au. 4. School of Applied Psychology, Griffith University, Gold Coast, QLD, Australia; Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. Electronic address: D.Shum@griffith.edu.au. 5. Faculty of Health Sciences and Medicine, Bond University QLD 4229, Australia. Electronic address: sbrandis@bond.edu.au. 6. School of Information and Communication Technology, Griffith University, Gold Coast, QLD 4222, Australia. Electronic address: v.muthu@griffith.edu.au. 7. School of Information and Communication Technology, Griffith University, Gold Coast, QLD 4222, Australia. Electronic address: b.stantic@griffith.edu.au. 8. Faculty of Engineering and Information Technology, University of Technology Sydney, Australia. Electronic address: Michael.Blumenstein@uts.edu.au. 9. School of Medical Science, Griffith University, Gold Coast, QLD 4222, Australia. Electronic address: j.headrick@griffith.edu.au.
Abstract
BACKGROUND: Biological pathways underlying major depressive disorder (MDD) can be viewed as systems biology networks. The psycho-immune-neuroendocrine (PINE) network comprises central nervous, immune, endocrine and autonomic systems, integrating biological mechanisms of MDD. Such networks exhibit recurrent motifs with specific functions, including positive and negative feedback loops, and are subject to critical transitions, influenced by feedback loop transitions (FLTs). AIMS: We aim to identify critical feedback loops and their FLTs, as well sentinel network nodes (SNNs), key network nodes that drive FLTs, within the PINE network. Examples of biomarkers are provided which may reflect early warning signs of impending critical transition to MDD. RESULTS: Disruption of homeostatic feedback loops reflects the physiological transition to MDD. Putative FLTs are identified within hypothalamic-pituitary-adrenal (HPA) and sympathetic-parasympathetic axes, the kynurenine pathway, gut function and dysbiosis. CONCLUSIONS: Progression from health to disease is driven by FLTs in the PINE network, which is likely to undergo changes characteristic of system instability. Biomarkers of system instability may effectively predict the critical transition to MDD.
BACKGROUND: Biological pathways underlying major depressive disorder (MDD) can be viewed as systems biology networks. The psycho-immune-neuroendocrine (PINE) network comprises central nervous, immune, endocrine and autonomic systems, integrating biological mechanisms of MDD. Such networks exhibit recurrent motifs with specific functions, including positive and negative feedback loops, and are subject to critical transitions, influenced by feedback loop transitions (FLTs). AIMS: We aim to identify critical feedback loops and their FLTs, as well sentinel network nodes (SNNs), key network nodes that drive FLTs, within the PINE network. Examples of biomarkers are provided which may reflect early warning signs of impending critical transition to MDD. RESULTS: Disruption of homeostatic feedback loops reflects the physiological transition to MDD. Putative FLTs are identified within hypothalamic-pituitary-adrenal (HPA) and sympathetic-parasympathetic axes, the kynurenine pathway, gut function and dysbiosis. CONCLUSIONS: Progression from health to disease is driven by FLTs in the PINE network, which is likely to undergo changes characteristic of system instability. Biomarkers of system instability may effectively predict the critical transition to MDD.
Authors: Carla M Patist; Nicolas J C Stapelberg; Eugene F Du Toit; John P Headrick Journal: Cogn Affect Behav Neurosci Date: 2018-12 Impact factor: 3.282