03 Dec 20. Featured Paper

Structural brain correlates of serum & epigenetic markers of inflammation in major depressive disorder.

Link to paper on Brain, Behavior & Immunity

Authors

Claire Green, Xueyi Shen, Anna J. Stevenson, Eleanor L. S. Conole, Mathew A. Harris, Miruna C. Barbu, Emma L. Hawkins, Mark J. Adams, Robert F. Hillary, Stephen M. Lawrie, Kathryn L. Evans, Rosie M. Walker, Stewart W. Morris, David J. Porteous, Joanna M. Wardlaw, J Douglas Steele, Gordon D. Waiter, Anca-Larisa Sandu, Archie Campbell, Riccardo E. Marioni, Simon R. Cox, Jonathan Cavanagh, Andrew M. McIntosh, Heather C. Whalley

Abstract

Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure & depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers.

Here, we report the first large-scale study of both serological & methylomic signatures of CRP (considered to represent acute & chronic measures of inflammation respectively) & their associations with depression status/symptoms, & structural neuroimaging phenotypes (T1 & diffusion MRI) in a large community-based sample (Generation Scotland; N_{MDD cases} = 271, N_controls = 609).

Serum CRP was associated with overall MDD severity, & specifically with current somatic symptoms- general interest (β = 0.145, P_FDR = 6 × 10⁻⁴) & energy levels (β = 0.101, P_FDR = 0.027), along with reduced entorhinal cortex thickness (β = −0.095, P_FDR = 0.037).

DNAm CRP was significantly associated with reduced global grey matter/cortical volume & widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external & internal capsules, β_FA= −0.12 to −0.14).

In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = −0.15 versus βaverage = 0.01 respectively).

These findings provide evidence for central effects of peripheral inflammation from both serological & epigenetic markers of inflammation, including in brain regions previously implicated in depression.

This suggests that these imaging measures may be involved in the relationship between peripheral inflammation & somatic/depressive symptoms.

Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies.

Keywords

• Brain morphology
• Brain structure
• C-reactive protein
• CRP
• Depression
• Inflammation
• Major depressive disorder
• Methylation
• MRI
• White matter integrity