Journal of Neurology and Psychology

Research Article

PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV

Haddadi S1, Jordan-Sciutto KL2, Akay-Espinoza C2, Grelotti D3, Letendre SL4, Tang B3 and Ellis RJ5

1Warren College, University of California, San Diego, La Jolla, CA 92093, USA
2Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA
4Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
5Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
*Address for Correspondence Ellis RJ, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; E-mail: roellis@health.ucsd.edu
Submission: January 04, 2023
Accepted: March 03, 2023
Published: March 09, 2023
Copyright: © 2023 Haddadi S, 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: Depression is a debilitating and difficult-to-treat condition in people with HIV (PWH) despite viral suppression on antiretroviral therapy (ART). Depression is associated with activation of the PKR-like ER kinase (PERK) pathway, which regulates protein synthesis in response to metabolic stress. We evaluated common PERK haplotypes that influence PERK expression in relation to depressed mood in PWH.
Methods: PWH from 6 research centers were enrolled in the study. Genotyping was conducted using targeted sequencing with TaqMan. The major PERK haplotypes A, B, and D were identified. Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II). Covariates including genetically-defined ancestry, demographics, HIV disease/treatment parameters and antidepressant treatments were assessed. Data were analyzed using multivariable regression models.
Results: A total of 287 PWH with a mean (SD) age of 57.1±7.8 years were enrolled. Although the largest ethnic group was non- Hispanic white (n=129, 45.3%), African-American (n=124, 43.5%) and Hispanic (n=30, 10.5%) made up over half the sample. 20.3% were female and 96.5% were virally suppressed. Mean BDI-II was 9.6±9.5, and 28.9% scored above the cutoff for mild depression (BDI-II>13). PERK haplotype frequencies were AA57.8%, AB25.8%, AD 10.1%, and BB4.88%. PERK haplotypes were differentially represented according to genetic ancestry (p=6.84e-6). BDI-II scores were significantly higher in participants with the AB haplotype (F=4.45, p=0.0007).This finding was robust to consideration of potential confounds.
Conclusion: PERK haplotypes were associated with depressed mood in PWH.Consequently, pharmacological targeting of PERKrelated pathways might amelioratedepression in PWH.