Immunometabolic dysregulation associates with brain atrophy in depression and predates illness onset
Poster No:
414
Submission Type:
Abstract Submission
Authors:
Ye Tian1, Corey Giles2, Vanessa Cropley3, Andrew Zalesky4
Institutions:
1Department of Psychiatry, The University of Melbourne, Melbourne, Australia, 2Baker Heart and Diabetes Institute, Melbourne, Australia, 3Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia, 4Systems Lab, Department of Psychiatry, The University of Melbourne, Melbourne, Australia
First Author:
Co-Author(s):
Andrew Zalesky
Systems Lab, Department of Psychiatry, The University of Melbourne
Melbourne, Australia
Systems Lab, Department of Psychiatry, The University of Melbourne
Melbourne, Australia
Introduction:
Depression often presents with co-occurring physical health conditions, including heart disease, diabetes and obesity. While dysregulation of the immunometabolic system is posited to underpin several of these physical comorbidities, the prevalence and course of immunometabolic dysregulation in depression is poorly understood and its impact on structural brain changes linked to the disorder is unknown. We sought to i) evaluate depression-related immunometabolic dysfunction over time and across illness stages; ii) test whether the dysfunction is prodromal, and iii) establish the extent to which peripheral immunometabolic dysfunction relates to brain structure in depression.
Methods:
We studied a subset of UK Biobank participants with assays of metabolomics that assessing peripheral inflammation, lipoprotein and lipids, fatty acids, amino acids, glycolysis metabolites and various low-molecular weight metabolites at baseline (n=259,367 mean age 57.1 ± 8.1 years) and during the second visit at 2-6 years follow-up (n=15,053 mean age 62.0 ± 7.4 years). Structural brain phenotypes were derived from T1-weighted MRI acquired during the third visit (4-14 years following the initial assessment) and were available for 27,446 individuals (mean 64.6 ± 7.7). We identified 45,767 individuals who had reported depression at or prior to the baseline assessment, forming a group that we refer to as existing depression, and 24,384 individuals who reported depression afterwards, referred to as the prodromal depression group. A healthy comparison group (HC, n=27,636, mean age: 53.8 ± 8.0 years) included individuals with no existing major medical or mental health conditions at baseline and follow-up visits.
Results:
We found markedly different immune and metabolomics profiles in individuals with established depression, compared to healthy individuals (Fig. 1). We found that depression is most strongly associated with i) elevated inflammation, as indicated by increased c-reactive protein, glycoprotein acetyls and leukocyte count; ii) increased plasma level of very-low-density lipoprotein, particularly large to very large particles and their lipid composition; iii) increased plasma level of triglycerides across all lipoprotein subclasses; and iv) decreased plasma level of HDL, particularly large to very large particles, and its lipid composition. These findings implicate profound depression-related changes in immunometabolism. Importantly, we found that peripheral immune and metabolic dysregulation was evident before the onset of depression (i.e., at the prodromal stage), albeit slightly reduced effect sizes. We also found widespread alteration in the strength of coupling between pairs of metabolites in depression compared to healthy individuals. Altered glycolysis coupling was most implicated in the network analysis. Finally, we show that peripheral immunometabolic dysfunction, particularly elevated inflammation, is associated with brain gray matter atrophy (Fig. 2).
·Fig 1. Immunometabolic profiles in depression
·Fig 2. Metabolomic-brain associations in depression
Conclusions:
In conclusion, our work reveals persistent and systemic changes in peripheral immunometabolic profile in depression over time and across illness stages. Our findings suggest that disturbances in peripheral immunometabolic regulation are widespread and may confer the risk of depression development and influence brain structure underpinning the neuropathology of depression. Early detection and intervention on normalising immunometabolic dysfunction may mitigate the risk of depression and improve depression prognosis.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Blood
MRI
Other - Depression; Metabolomics; Inflammation
1|2Indicates the priority used for review
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