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Approved research

Neuroinflammatory biomarkers of depression and its neurobiological underpinnings

Principal Investigator: Mr Richard Bethlehem
Approved Research ID: 48943
Approval date: October 2nd 2019

Lay summary

Depression is an extremely heterogenous condition with symptom severity and response to treatment varying wildly across individuals affected. With an estimated lifetime prevalence of round 14% (Kessler & Bromet, 2014) it is of vital importance to better understand the biology underpinning this variation so that we can; A) provide better informed treatment outcome and plans in relation to existing drugs and B) provide a more targeted search for novel drug targets. There is ample evidence in literature to suggest that neuroinflammation is associated, and may even cause, depression. To further investigate this link the present study proposes to study how inflammation in depression interact with brain structure and function and how more accessible peripheral biomarkers such as blood counts and accelerometry might be used to stratify individuals with depression. Specifically, we hypothesize that: (i) peripheral inflammation, defined by blood levels of C-reactive protein (CRP), is associated with central nervous system inflammation and abnormal brain structure and function. (ii) Peripheral blood cell counts are associated with depressive symptom severity and symptom profiles. (iii) Among participants with inflamed major depressive disorder (as indexed by raised CRP), there are distinct peripheral immune profiles associated with either a greater innate immune or adaptive immune bias. (iv) therapeutic resistance to monoaminergic (MA) antidepressant drugs is associated with peripheral biomarkers indicating abnormal activation of the innate immune system We will test these hypotheses by combining multi-modal brain imaging data with available biomarker and clinical data.