The Original GENIAL Model
Our original GENIAL model \cite{Kemp_2017} (Fig \ref{div-134290}) emphasised the pathways to health and wellbeing versus ill-health and premature mortality, highlighting key roles for vagal function and social interaction along these pathways. The role for the vagus nerve – indexed by heart rate variability (HRV) – built on well-established theoretical models including polyvagal theory \citep{Porges:2011wv,PORGES_1995,Porges_2001,Porges_2003,Porges_2007}, which emphasises a role for the myelinated vagus nerve – in particular – in social engagement, and the neurovisceral integration model \cite{Thayer_2000,Thayer_2009,Thayer_2009a}, which lays a neurophysiological foundation for understanding mind-brain-body linkage. The recent extension of the neurovisceral integration model named the 'Neurovisceral Integration Across a Continuum of Time' or 'NIACT' \citep*{Kemp_2017a} laid a temporal framework for understanding linkage between emotion and - over time - mortality, bridging the gap between psychological science and epidemiology. This model was motivated by research \citep{Tracey_2002,Jarczok_2014,Jandackova_2016,Kemp_2016} highlighting a mediating role of the vagus nerve over downstream health-relevant outcomes. NIACT provides a theoretical framework within which these disparate findings can be understood. Kevin Tracey, an American neurosurgeon identified the ‘cholinergic anti-inflammatory reflex’ \cite{Tracey_2002}, regulated by the vagus nerve, which if impaired may contribute to a host of conditions including poor metabolic outcomes, cardiovascular disease and associated mortality \cite{Hillebrand_2013,Wulsin_2015}. The efferent vagus nerve achieves this through interaction with the peripheral \(\alpha\)7 subunit-containing nicotinic acetylcholine receptors expressed on macrophages. See \citet{Pavlov_2003} for a detailed review of the cholinergic anti-inflammatory pathway. Jarczok and colleagues \cite{Jarczok_2014} demonstrated that reduced vagal function (indexed by lower heart rate variability) predicts increased levels of C-reactive protein four years later, providing in vivo support for this cholinergic anti-inflammatory pathway in humans. Kemp and colleagues employed modern mediation modelling on the ELSA-Brasil cohort \cite{Kemp_2016}, demonstrating that vagal function lies upstream of insulin resistance and carotid-intima media thickness, an early marker of atherosclerosis, which together leads to cognitive dysfunction. Jandackova and colleagues applied cross-lagged analysis to the Whitehall Stress and Health Study cohort \cite{Jandackova_2016} and observed that vagal function precedes development of depression over a ten-year follow-up period. These studies are part of a larger body of work summarised previously \cite{Kemp_2017,Kemp_2017a,ah2018} that demonstrate how early changes in vagal functioning may contribute to downstream changes in wellbeing. The GENIAL model \cite{Kemp_2017} further developed NIACT \cite{Kemp_2017a} by highlighting the role of social relationships along the pathways to health and wellbeing, in addition to the moderating role of health behaviours (e.g. diet, physical activity, sleep, smoking and alcohol consumption) and sociostructural factors (e.g. inequality, collective efficacy). The GENIAL model draws and builds on research which highlights: 1) the role of social identity in the development of meaning and purpose in life and its impacts on health and wellbeing \cite{Haslam_2008}; 2) that positive social ties reduce risk of early death to a degree that is equivalent to the effects of smoking cessation \cite{Holt_Lunstad_2010}, and 3) the impact of sociostructural factors such as inequality \cite{Kondo_2009} and collective efficacy \cite{Bandura_2004} on individuals' capacity to achieve health-related goals. These ideas are further developed in the following sections.