Elevated Depressive Symptoms Are a Stronger Predictor of Executive Dysfunction in HIV-Infected Women Than in Men

Abstract

Background: HIV-infected (HIV+) women appear to be more vulnerable to neurocognitive impairment than HIV+ men, perhaps in part due to mental health factors. We assessed the association between elevated depressive symptoms and NCI among HIV+ and HIV-uninfected (HIV-) women and men. Setting: Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS). Methods: 858 HIV+ (429 women; 429 men) and 562 HIV-(281 women; 281 men) completed the Center for Epidemiologic Studies Depression (CES-D; 16 cutoff) scale and measures of psychomotor speed/attention, executive, and motor function over multiple visits (or time points). WIHS and MACS participants were matched according to HIV status, age, race/ethnicity, and education. Generalized linear mixed models were used to examine interactions between biological sex, HIV-serostatus, and depression on impairment (T-scores<40) after covariate adjustment. Results: Despite a higher frequency of depression among males, the association between depression and executive function differed by sex and HIV-serostatus. HIV+ women with depression had 5 times the odds of impairment on a measure of executive control and inhibition

Sex Differences in the Patterns and Predictors of Cognitive Function in HIV

“…Although the prevalence of a current or lifetime diagnosis of MDD did not differ between WWH and MWH, MDD was an important risk factor of demonstrating Global weaknesses with spared verbal recognition (Profile 2) compared to the profile demonstrating only Weakness in motor function (Profile 1). This finding aligns with our work demonstrating that MDD may have a greater impact in women compared to men (25). Our work indicates that HIV comorbid with depression affects certain cognitive domains including cognitive control, and that these effects are largest in women.…”

“…Biological differences may also contribute to sex differences in the pattern and magnitude of cognitive impairment in PWH including disease characteristics, brain structure/function, sex steroid hormones and female-specific hormonal milieus (e.g., pregnancy, menstrual cycle, menopause transition). There is also evidence to suggest that WWH may be more cognitively susceptible than MWH to the effects of mental health factors (25).…”

“…WWH tend to have a higher prevalence of psychosocial risk factors including poverty, low literacy levels, low educational attainment, substance abuse, poor mental health, and barriers to health care services (10,22) as compared to MWH. These psychosocial risk factors may have biological effects on the brain that lead to reduced cognitive reserve among WWH (23,24) as evidenced by findings of greater susceptibility of cognitive function to the effects of mental health factors (e.g., depression) among WWH vs. MWH (25). Additionally, biological factors such as sex steroid hormones (e.g., estrogen, testosterone) and female-specific hormonal milieus (e.g., pregnancy, menstrual cycle, menopause transition) may contribute to sex differences in cognitive test performance in PWH.…”

Sex Differences in Neurocognitive Function in Adults with HIV: Patterns, Predictors, and Mechanisms

“…Few large-scale HIV cohort studies assess sex differences in mental health risk factors and disorders on NCI. We examined the association of elevated depressive symptoms with NCI in the WIHS and MACS [15]. Although MLWH showed a higher frequency of elevated depressive symptoms than WLWH (perhaps due to sexual minority status), WLWH with elevated depressive symptoms had 5 times the odds of impairment in executive control/inhibition versus HIV− women with elevated depressive symptoms, and 3 times the odds of impairment on that measure versus MLWH with elevated depressive symptoms.…”

“…Compared to MLWH, WLWH may be at greater risk for neurocognitive impairment (NCI) due in part to a disproportionate burden of poverty, low literacy levels, low educational attainment, substance abuse, poor mental health, barriers to health care services, and environmental exposures prevalent in predominantly minority urban communities [11, 13, 14••]. There is also evidence to suggest that WLWH may be more cognitively susceptible than MLWH to the effects of the same challenges [15]. In addition, biological factors such as sex steroid hormones (e.g., estrogen, progesterone, testosterone) and female-specific hormonal milieus (e.g., pregnancy, menstrual cycle, menopause transition) may contribute to sex differences in the pattern and magnitude of HIV-associated alterations in neurocognitive function.…”