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J Eval Clin Pract. 2017 Feb;23(1):199-208. doi: 10.1111/jep.12587. Epub 2016 Jul 15.

'Multimorbidity' as the manifestation of network disturbances.

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Department of General Practice, Newcastle - Australia, The University of Newcastle, Wamberal, NSW, Australia.
Department of Psychology, The University of North Carolina at Charlotte, Charlotte, NC, USA.
Department of Medicine, Nursing and Allied Health, Monash Health, Clayton - Australia.
Division of Behavioral Medicine, Department of Psychiatry, Department of Neurology and CTNI, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.


We argue that 'multimorbidity' is the manifestation of interconnected physiological network processes within an individual in his or her socio-cultural environment. Networks include genomic, metabolomic, proteomic, neuroendocrine, immune and mitochondrial bioenergetic elements, as well as social, environmental and health care networks. Stress systems and other physiological mechanisms create feedback loops that integrate and regulate internal networks within the individual. Minor (e.g. daily hassles) and major (e.g. trauma) stressful life experiences perturb internal and social networks resulting in physiological instability with changes ranging from improved resilience to unhealthy adaptation and 'clinical disease'. Understanding 'multimorbidity' as a complex adaptive systems response to biobehavioural and socio-environmental networks is essential. Thus, designing integrative care delivery approaches that more adequately address the underlying disease processes as the manifestation of a state of physiological dysregulation is essential. This framework can shape care delivery approaches to meet the individual's care needs in the context of his or her underlying illness experience. It recognizes 'multimorbidity' and its symptoms as the end product of complex physiological processes, namely, stress activation and mitochondrial energetics, and suggests new opportunities for treatment and prevention. The future of 'multimorbidity' management might become much more discerning by combining the balancing of physiological dysregulation with targeted personalized biotechnology interventions such as small molecule therapeutics targeting specific cellular components of the stress response, with community-embedded interventions that involve addressing psycho-socio-cultural impediments that would aim to strengthen personal/social resilience and enhance social capital.


complex adaptive systems; mitochondria; multimorbidity; nonlinear dynamics; philosophy of health; philosophy of medicine; psychoneuroimmunology

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