Low Levels of Brain-derived Neurotrophic Factor (BDNF) in People With HIV are not Associated With Depression: A Cross-sectional Analysis
Ronald Ellis1, David Grelotti3, Anna Laird2, Jerel Fields2
1Neurosciences and Psychiatry, 2Psychiatry, UC San Diego, 3University of California San Diego
Objective:
To examine serum concentrations of proBDNF and mature BDNF according to HIV serostatus, lifetime major depressive disorder (MDD), current depressive symptoms, and antidepressant use in a well-characterized cohort of people with and without HIV (PWH, PWoH).
Background:
Depression is common in PWH, but the relationship between HIV, depression, and circulating brain-derived neurotrophic factor (BDNF) remains unclear.
Design/Methods:
This cross-sectional study included 281 participants (200 PWH, 81 PWoH) from the HIV Neurobehavioral Research Program (2006–2023) with serum samples, Beck Depression Inventory-II scores, and psychiatric assessments. Serum proBDNF and mature BDNF were measured by ELISA and log10-transformed. Multivariable linear regression tested associations with HIV serostatus, MDD, antidepressant use, age, and sex, including interaction terms for HIV effects.
Results:
Groups were similar in age (47.7 vs 48.7 years, p = 0.60) and education (13.2 vs 13.6 years, p = 0.25) but differed by sex (18.0% vs 33.3% women, p = 0.008). Among PWH, 77.0% were on ART and 67.5% were virally suppressed. Depression burden was greater in PWH (BDI-II 13.9 vs 10.6, p = 0.031). PWH had lower serum proBDNF and mature BDNF than PWoH. Mean proBDNF was 0.454 log10 units lower (Cohen’s d = −0.49, p = 6.9e−04) and mature BDNF 0.0683 log10 units lower (Cohen’s d = −0.48, p = 9.0e−04). Lifetime MDD, current MDD, depressive symptom severity, and antidepressant use showed no associations with either isoform (all p > 0.39), and no HIV interactions were detected. Differences by HIV serostatus persisted after adjustment for sex, and the higher proportion of women among PWoH would be expected to attenuate, not exaggerate, this effect.
Conclusions:
HIV was associated with lower circulating proBDNF and mature BDNF, while depression-related measures were unrelated to either isoform. Peripheral BDNF does not appear to index depression in PWH, suggesting that depression in this population arises through mechanisms other than BDNF deficiency.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.