@article{97b290f13eaf47f58f86c9a537c62e14,
title = "Immunological biomarkers associated with brain structure and executive function in late-life depression: exploratory pilot study",
abstract = "Objective: Several immunological biomarkers are altered in late-life major depressive disorder (LLD). Immunological alterations could contribute to LLD's consequences, but little is known about the relations between specific immunological biomarkers and brain health in LLD. We performed an exploratory pilot study to identify, from several candidates, the specific immunological biomarkers related to important aspects of brain health that are altered in LLD (brain structure and executive function). Methods: Adults (n = 31) were at least 60 years old and had major depressive disorder. A multiplex immunoassay assessed 13 immunological biomarkers, and we examined their associations with structural MRI (grey matter volume and white matter hyperintensity volume (WMH)) and executive function (Color–Word Interference and Trail-Making tests) measures. Results: Vascular endothelial growth factor (VEGF) and the chemokine eotaxin had significant negative associations with grey matter volume (VEGF: n = 31, r = −0.65; eotaxin: n = 29, r = −0.44). Tumor necrosis factor alpha (TNF-α) had a significant positive relationship with WMHs (n = 30, r = 0.52); interferon-γ (IFN-γ) and macrophage inflammatory protein-1α (MIP-1α) were also significantly associated with WMHs (IFN-γ: n = 31, r = 0.48; MIP-1α: n = 29, r = 0.45). Only eotaxin was associated with executive function (set-shifting performance as measured with the Trail-making test: n = 33, r = −0.43). Conclusions: Immunological markers are associated with brain structure in LLD. We found the immunological correlates of grey and white matter differ. Prospective studies are needed to evaluate whether these immunological correlates of brain health increase the risk of LLD's consequences. Eotaxin, which correlated with both grey matter volume and set-shifting performance, may be particularly relevant to neurodegeneration and cognition in LLD.",
keywords = "MRI, brain structure, depression, immunology, inflammation, neuroimaging",
author = "Smagula, {Stephen F.} and Lotrich, {Francis E.} and Aizenstein, {Howard J.} and Diniz, {Breno S.} and Jeffrey Krystek and Wu, {Gregory F.} and Mulsant, {Benoit H.} and Butters, {Meryl A.} and Reynolds, {Charles F.} and Lenze, {Eric J.}",
note = "Funding Information: The funding sources had no role in study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the report for publication. EJL is the current recipient of grant/research support from NIH (NIA, NCCIH, NIMH, OBSSR), FDA, McKnight Brain Research Foundation, Taylor Family Institute for Innovative Psychiatric Research, Barnes Jewish Foundation, Takeda, and Lundbeck, and is the past recipient of research support from Roche, and the Sidney R. Baer Foundation. BHM currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the US National Institute of Health (NIH), the CAMH Foundation, Eli Lilly (medications for a NIH-funded clinical trial), and Pfizer (medications for a NIH-funded clinical trial). Within the past three years he has also received research support from Bristol-Myers Squibb (medications for a NIH-funded clinical trial) and Pfizer/Wyeth (medications for a NIH-funded clinical trial). He directly own stocks of General Electric (less than $5000). CFR reports receiving pharmaceutical support for NIH-sponsored research studies from Bristol-Myers Squibb, Forest, Pfizer, and Lilly; receiving grants from the National Institute of Mental Health, National Institute on Aging, National Center for Minority Health Disparities, National Heart Lung and Blood Institute, Center for Medicare and Medicaid Services (CMS), Patient Centered Outcomes Research Institute (PCORI), the Commonwealth of Pennsylvania, the John A Hartford Foundation, National Palliative Care Research Center (NPCRC), Clinical and Translational Science Institute (CTSI), and the American Foundation for Suicide Prevention; and serving on the American Association for Geriatric Psychiatry editorial review board. CFR has received an honorarium as a speaker from MedScape/WEB MD, and is the co-inventor (Licensed Intellectual Property) of Psychometric analysis of the Pittsburgh Sleep Quality Index (PSQI) PRO10050447 (PI: Buysse). We would like to thank Ms. Courtney Wilson and Dr. Diane Bender at the Center for Human Immunology and Immunotherapy Programs at Washington University, which in part supported this work, for their expertise in cytokine and chemokine analysis. Funding Information: Trial Registration: clinicaltrials.gov identifier NCT00892047. Supported by the three R01s at Pittsburgh (R01 MH083660), Washington University in St. Louis (R01 MH083648), and the Center for Addiction and Mental Health, Toronto (R01 MH083643), Center Core grant P30 MH090333, P60 MD000207, UL1RR024153, UL1TR000005, and the UPMC Endowment in Geriatric Psychiatry. The imaging study was supported by R01 MH076079. SFS has been supported by Research Training grant T32 MH019986. Experimental support was also partially provided by the Immunomonitoring Laboratory of the Rheumatic Diseases Core Center (NIH P30AR048335) and by R01MH090250 to FL. Publisher Copyright: Copyright {\textcopyright} 2016 John Wiley & Sons, Ltd.",
year = "2017",
month = jun,
doi = "10.1002/gps.4512",
language = "English",
volume = "32",
pages = "692--699",
journal = "International Journal of Geriatric Psychiatry",
issn = "0885-6230",
number = "6",
}