5 research outputs found

    From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression

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    © 2018 Elsevier Ltd 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

    The contribution of major depression to the global burden of ischemic heart disease: A comparative risk assessment

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    Background: Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology. Methods: A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010.Results: The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest. Conclusions: The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event
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