Neighbourhood-level deprivation and morphological changes within the limbic stress circuit: results from a prospective, population-based, cohort study

Queirazza, F., Krishnadas, R. , McLean, J. and Cavanagh, J. (2014) Neighbourhood-level deprivation and morphological changes within the limbic stress circuit: results from a prospective, population-based, cohort study. Lancet, 383(s1), s85. (doi: 10.1016/S0140-6736(14)60348-2)

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Background Socioeconomic deprivation has been associated with chronic stress and poor mental health. In this study we investigated whether neighbourhood-level deprivation is associated with volumetric differences in a group of limbic forebrain structures—the hippocampus, amygdala, and ventromedial prefrontal cortex—which are implicated in the top-down modulation of the stress response. In addition we examined the role of circulating inflammatory markers in mediating the above associations.<p></p> Methods Participants were recruited as part of a larger prospective population-based cohort study. Each participant attended for two visits over 2·5 years between December, 2005, and May, 2008. Selection of participants was based on the Scottish Index of Multiple Deprivation 2004 and sampling was stratified to achieve a roughly equal distribution of the 666 participants across male and female participants and age groups within the most and least deprived areas of Glasgow, UK. Of 327 male participants, 140 consented to structural neuroimaging, and 42 middle-aged (mean 51 years, SD 8·7) neurologically healthy adults (21 from least deprived and 21 from most deprived areas) were randomly selected. Biomarkers of interest included cortisol, high-sensitivity C-reactive protein, intercellular adhesion molecule 1, fibrinogen, D-dimer, and interleukin 6. On the basis of the averaged Z scores of the biomarkers, we calculated an inflammatory index that we used as mediator variable.<p></p> Findings In multivariate analysis (repeated measures ANCOVA), neighbourhood deprivation predicted volumes of the regions of interest (F(1,37)=10·33, p=0·003, η2p=0·22). At the univariate level, neighbourhood deprivation was associated with smaller volumes in the right hippocampus (t=3·252, p=0·002, η2p=0·222) and right ventromedial/orbitofrontal cortex (t=2·275, p=0·029, η2p=0·12), but not in the left hippocampus, left ventromedial/orbitofrontal cortex, left and right amygdala, and left and right perigenual and subgenual anterior cingulate. The inflammatory index mediated the association between neighbourhood deprivation and volume of the right ventromedial/orbitofrontal cortex (β=−247·67, SE 134·86, 95% CI −582·76 to −32·99). No mediation effect by the inflammatory index was found in the association between neighbourhood deprivation and the right hippocampus.<p></p> Interpretation The finding of an association between smaller right hippocampus and neighbourhood deprivation is consistent with previous reports. To the best of our knowledge, ours is the first human study to report an association between neighbourhood deprivation and smaller volume in the right ventromedial/orbitofrontal cortex. Taking into account animal and human data, we speculate that the observed right-lateralised morphological changes in the hippocampus and ventromedial/orbitofrontal cortex could be due to an asymmetrical distribution of stress biomediators in the brain. It is also tempting to speculate that the observed structural abnormalities in the above regions might provide a neurobiological account of some of the cognitive and behavioural deficits that have been linked to lower socioeconomic status. Finally, aberrant activation of inflammatory pathways provides a potential mechanistic link between neighbourhood deprivation and structural remodelling of the brain.<p></p>

Item Type:Articles (Other)
Glasgow Author(s) Enlighten ID:Krishnadas, Dr Rajeev and Queirazza, Dr Filippo and Cavanagh, Professor Jonathan
Authors: Queirazza, F., Krishnadas, R., McLean, J., and Cavanagh, J.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Lancet
Publisher:The Lancet Publishing Group
ISSN (Online):1474-547X

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