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

Rubin, Leah H. PhD, MPHa,b; Springer, Gayle MLAb; Martin, Eileen M. PhDc; Seaberg, Eric C. PhDb; Sacktor, Ned C. MDa; Levine, Andrew PhD, ABPPd; Valcour, Victor G. MD, PhDe; Young, Mary A. MDf; Becker, James T. PhDg; Maki, Pauline M. PhDh

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1, 2019 - Volume 81 - Issue 3 - p 274–283
doi: 10.1097/QAI.0000000000002029

Background: HIV-infected (HIV+) women seem to be more vulnerable to neurocognitive impairment (NCI) 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 and Multicenter AIDS Cohort Study.

Methods: Eight hundred fifty-eight HIV+ (429 women; 429 men) and 562 HIV− (281 women; 281 men) completed the Center for Epidemiologic Studies Depression (16 cutoff) Scale and measures of psychomotor speed/attention, executive, and motor function over multiple visits (or time points). Women's Interagency HIV Study and Multicenter AIDS Cohort Study 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 men, 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 versus HIV− depressed women and 3 times the odds of impairment on that measure versus HIV+ depressed men. Regardless of group status, depression was associated with greater impairment on processing speed, executive (mental flexibility), and motor function (P's < 0.05).

Conclusions: Depression contributes to NCI across a broad range of cognitive domains in HIV+ and HIV− individuals, but HIV+ depressed women show greater vulnerabilities in executive function. Treating depression may help to improve cognition in patients with HIV infection.

aDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD;

bDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

cDepartment of Psychiatry, Rush University Medical Center, Chicago, IL;

dDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA;

eDepartment of Neurology, University of California San Francisco, San francisco, CA;

fDepartment of Medicine, Georgetown University, Washington, DC;

gDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA; and

hDepartments of Psychiatry and Psychology, University of Illinois at Chicago College of Medicine, Chicago, IL.

Correspondence to: Leah H. Rubin, PhD, MPH, Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Meyer 6-113, Baltimore, MD 21287-7613 (e-mail:

Supported by the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Deafness and Communication Disorders (NIDCD), and the Office of Research on Women's Health (ORWH). This work was also supported by the Johns Hopkins University NIMH Center for novel therapeutics for HIV-associated cognitive disorders (P30MH075773).

The authors have no conflicts of interest to disclose.

The complete set of author names of the Neuropsychology Working Groups of the Women's InterAgency HIV Study and the Multicenter AIDS Cohort Study are listed in the acknowledgment section.

Received November 26, 2018

Accepted February 20, 2019

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