Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men

Abstract

Objective Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid, nongenomic and slow, genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD, but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men. Methods In a double-blind, placebo-controlled, cross-over study, we examined the time-dependent effects of a single low dose of hydrocortisone (10mg; LDH) on cognition in 45 HIV-infected men. Participants were randomized to receive either LDH or placebo, and one month later were given the opposite treatment. At each intervention session, cognition was assessed 30 minutes (assessing nongenomic effects) and 4 hours (assessing genomic effects) after pill administration. Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session. Results Compared to placebo, LDH doubled salivary cortisol levels. Cortisol returned to baseline 4 hours post-administration. At the 30-minute assessment, LDH enhanced verbal learning compared to placebo. Greater increases in cortisol were associated with greater enhancements in verbal learning. LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point. Conclusion The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men. The non-enduring nature of this enhancement may limit its clinical utility, but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning.

Early life trauma and social processing in HIV: the role of neuroendocrine factors and inflammation

“…Thus, 72% (58 of 81) of participants were included in the analysis. Importantly, the sociodemographic characteristics of the 58 individuals were similar to the 81 participants in age (mean = 33.7 versus 34.3 years), race (93.1% Black versus 93.8%), and ELT exposure to the larger sample (50% versus 51.9%) (54,55).…”

“…This secondary analysis included data from PWH during the placebo condition of a randomized, double-blind, placebo-controlled crossover pharmacologic challenge (10 mg of hydrocortisone versus placebo) ( 54 , 55 ) who provided blood and saliva samples and also completed the FEPT. Data were collected between March 2013 and March 2017.…”

“…See Refs. ( 54 , 55 ) for details regarding saliva collection procedures. Samples were assayed for cortisol with an EIA kit by Salimetrics.…”

Stressing the need for validated measures of cortisol in HIV research: A scoping review

“…Rubin et al reported that higher levels of afternoon salivary cortisol were associated with poorer performance on cognitive tests in women living with HIV but not in men living with HIV (Table 5) [36]. They also found that a single dose of hydrocortisone improved learning in both men and women living with HIV but more so in women [44,45]. This may be partially due to sex differences in the HPA axis and differential exposure to psychological stress between men and women living with HIV.…”

The Association Between Peripheral Oxytocin Levels and Depressive Symptoms in People With HIV

“…Seventy-nine PWH (35 women, 44 men) were included in a secondary analysis from a double-blind, randomized-controlled crossover study on the effect of single administration of 10 mg of low-dose hydrocortisone on cognition in PWH. Information on the parent study has been reported elsewhere ( 42 , 43 ), and only data from the day of placebo administration were included in the analyses. Inclusion criteria included HIV-seropositive status confirmed by the individual’s medical record, an age range of 18 to 45 years, English as a first language, and use of the same combination antiretroviral therapy for at least 3 months.…”