Journal of Neurology and Psychology

Research Article

Astrocyte Activation is A Potential Mechanism Underlying Depressed Mood and Apathy in People with HIV

Ronald J. Ellis1*, Yan Fan2, David Grelotti3, Bin Tang3, Scott Letendre4 and Johnny J. He5

1Departments of Neurosciences and Psychiatry, University of California, San Diego, CA, United States
2Department of Ophthalmology, UT Southwestern Medical Center, Dallas TX, United States
3Department of Psychiatry, University of California, San Diego, CA, United States
4Departments of Medicine and Psychiatry, University of California, San Diego, CA, United States
5Department of Microbiology and Immunology, Chicago Medical School Rosalind Franklin University, North Chicago, IL, United States
*Address for Correspondence: Ronald J. Ellis, UCSD HNRC, 220 Dickinson Street Mail Code 8231, Suite B San Diego CA 92103-8231 E-mail: roellis@health.ucsd.edu
Submission: November 18, 2022
Accepted: December 20, 2022
Published: December 26, 2022
Copyright: © 2022 Ellis RJ, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Astrocytes become activated with certain infections, and this might alter the brain to trigger or worsen depressed mood. Indeed, astrocytes are chronically activated in people with HIV infection (PWH), who are much more frequently depressed than people without HIV (PWoH). A particularly disabling component of depression in PWH is apathy, a loss of interest, motivation, emotion, and goal-directed behavior. We tested the hypothesis that depression and apathy in PWH would be associated with higher levels of a biomarker of astrocyte activation, glial fibrillary acidic protein (GFAP), in cerebrospinal fluid (CSF).
Methods: We evaluated PWH in a prospective observational study using the Beck Depression Inventory-II (BDI-II) and additional standardized assessments, including lumbar puncture. We measured GFAP in CSF with a customized direct sandwich ELISA method. Data were analyzed using ANOVA and multivariable regression.
Results: Participants were 212 PWH, mean (SD) age 40.9±9.14 years, median (IQR) nadir and current CD4 199 (57, 326) and 411 (259, 579), 65.1% on ART, 67.3% virally suppressed. Higher CSF GFAP correlated with worse total BDI-II total scores (Pearson correlation r=0.158, p-value=0.0211), and with worse apathy scores (r=0.205, p=0.0027). The correlation between apathy/depression and GFAP was not influenced by other factors such as age or HIV suppression status.
Conclusions: Astrocyte activation, reflected in higher levels of CSF GFAP, was associated with worse depression and apathy in PWH. Interventions to reduce astrocyte activation -- for example, using a peptide-1 receptor (GLP-1R) agonist -- might be studied to evaluate their impact on disabling depression in PWH.