HIV 感染者糖皮质激素受体功能与认知表现

Glucocorticoid Receptor Function and Cognitive Performance in Women With HIV.

机构信息

From the Department of Neurology and Psychiatry (Rubin), Johns Hopkins University School of Medicine; Department of Epidemiology (Rubin, Springer, Gange), Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Emory University School of Medicine (Bekhbat); Department of Biostatistics and Bioinformatics, Rollins School of Public Health (Mehta), Emory University, Atlanta, Georgia; Department of Psychiatry, Psychology and Obstetrics & Gynecology (Maki), University of Illinois at Chicago, Chicago, Illinois; Departments of Medicine, Epidemiology & Population Health, and Obstetrics & Gynecology and Women's Health (Anastos), Albert Einstein College of Medicine, Bronx; Department of Neurology (Gustafson), SUNY-Downstate Health Sciences University, Brooklyn, New York; Department of Medicine (Spence), Georgetown University, Washington, DC; Institute for Health Promotion and Disease Prevention Research (Milam), University of Southern California, Los Angeles; Weill Institute for Neurosciences, Department of Neurology, and Division of Infectious Diseases (Chow), University of California, San Francisco, San Francisco, California; The Core Center, Bureau of Health Services of Cook County (Weber), Chicago, Illinois; and Department of Anatomy and Neurobiology, School of Medicine (Neigh), Virginia Commonwealth University, Richmond, Virginia.

出版信息

Psychosom Med. 2022 Oct 1;84(8):893-903. doi: 10.1097/PSY.0000000000001126. Epub 2022 Aug 20.

DOI:10.1097/PSY.0000000000001126

PMID:36044614

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9553273/

Abstract

OBJECTIVE

Alterations in glucocorticoid receptor (GCR) function may be a risk factor for cognitive complications among older people with human immunodeficiency virus (HIV). We evaluated whether HIV serostatus and age modify the GCR function-cognition association among women.

METHODS

Eighty women with HIV ( n = 40, <40 years of age [younger]; n = 40, >50 years of age [older]) and 80 HIV-uninfected women ( n = 40 older, n = 40 younger) enrolled in the Women's Interagency HIV Study completed a comprehensive neuropsychological test battery. Peripheral blood mononuclear cells collected concurrent with neuropsychological testing were assessed for GCR function. Multivariable linear regression analyses were conducted to examine whether a) HIV serostatus and age were associated with GCR function, and b) GCR function-cognition associations are moderated by HIV serostatus and age adjusting for relevant covariates.

RESULTS

Among older women, higher baseline FKBP5 expression level was associated with lower attention/working memory performance among women with HIV ( B = 6.4, standard error = 1.7, p = .0003) but not in women without HIV infection ( B = -1.7, standard error = 1.9, p = .37). There were no significant HIV serostatus by age interactions on dexamethasone (DEX)-stimulated expression of the genes regulated by the GCR or lipopolysaccharide-stimulated tumor necrosis factor α levels (with or without DEX stimulation; p values > .13). HIV serostatus was associated with GC target genes PER1 ( p = .006) and DUSP1 ( p = .02), but not TSC22D3 ( p = .32), after DEX stimulation.

CONCLUSIONS

Collectively, these data suggest that HIV serostatus and age may modify the influence of the GCR, such that the receptor is likely engaged to a similar extent, but the downstream influence of the receptor is altered, potentially through epigenetic modification of target genes.

摘要

目的

糖皮质激素受体（GCR）功能的改变可能是老年人类免疫缺陷病毒（HIV）感染者认知并发症的一个危险因素。我们评估了 HIV 感染状态和年龄是否会改变 GCR 功能与认知之间的关系，这种关系在女性中更为明显。

方法

80 名 HIV 阳性女性（n=40，<40 岁[年轻组]；n=40，>50 岁[年老组]）和 80 名 HIV 阴性女性（n=40 名年龄较大，n=40 名年龄较小）参加了妇女机构间 HIV 研究，完成了全面的神经心理学测试。在进行神经心理学测试的同时收集外周血单核细胞，评估 GCR 功能。采用多变量线性回归分析，检查 a）HIV 感染状态和年龄是否与 GCR 功能相关，b）在调整相关协变量后，GCR 功能-认知关联是否受 HIV 感染状态和年龄的调节。

结果

在年龄较大的女性中，较高的 FKBP5 表达水平与 HIV 阳性女性的注意力/工作记忆表现降低有关（B=6.4，标准误差=1.7，p=0.0003），但与未感染 HIV 的女性无关（B=-1.7，标准误差=1.9，p=0.37）。在接受地塞米松（DEX）刺激的 GCR 调节基因或脂多糖刺激的肿瘤坏死因子 α 水平（有或无 DEX 刺激）方面，DEX 刺激的基因表达无显著的 HIV 感染状态与年龄的相互作用（p 值>0.13）。DEX 刺激后，HIV 感染状态与 GC 靶基因 PER1（p=0.006）和 DUSP1（p=0.02）相关，但与 TSC22D3 无关（p=0.32）。