Depression Linked to Cognitive Dysfunction in HIV-Positive Women

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In early March at the Conference on Retroviruses and Opportunistic Infections in Seattle, Leah Rubin, Ph.D., M.P.H., associate professor at Johns Hopkins Bloomberg School of Public Health, discussed the link between depression and cognitive dysfunction in HIV-positive cisgender women.

Previous research comparing HIV-positive men and women has shown that HIV-positive women appear to be more vulnerable to cognitive impairment that affects attention, psychomotor speed, mental flexibility, and motor function. But researchers are still trying to figure out why. Rubin and her colleagues wanted to examine what role mental health issues such as depression might play in this gender imbalance.

Rubin's presentation was based on a study published in the March issue of the Journal of Acquired Immune Deficiency Syndrome (JAIDS). The study analyzed data from the Women's Interagency HIV Study (WIHS), a large prospective cohort study that began in 1993 to investigate the impact of HIV on women. It also used data from a similar, long-term study on men -- the Multicenter AIDS Cohort Study (MACS) -- which began in 1984.

The researchers looked at 858 people living with HIV (429 men and 429 women) and 562 HIV-negative individuals (281 men and 281 women). WIHS and MACS participants were matched according to HIV status, age, race/ethnicity, and education. The researchers then examined the interactions that sex assigned at birth, HIV status, and depression had with cognitive impairment scores.

The men in this study were more likely to have ever experienced depression than women, regardless of serostatus. This was a little surprising, because the prevalence of depression in women is generally higher than in men. Sexual orientation may explain why these results are different, according to Rubin and her colleagues. All of the men in the MACS study are gay or bisexual, whereas most of the women in the WIHS study are heterosexual. Previous research has shown that the prevalence of depression in sexual minorities is higher than in heterosexuals as a result of stigma and lack of social support, among other issues.

When broken down by serostatus, the study found that HIV-positive men have similar rates of depression as men who are HIV negative (50% versus 47%). The same, however, was not true of women, with 34% of HIV-positive women saying they had ever experienced depression compared to only 25% of HIV-negative women.

Moreover, though depression was associated with greater impairment in processing speed, mental flexibility, and motor function in all groups, the impact on executive function was most pronounced among HIV-positive women with depression. Specifically, the study found that HIV-positive women with depression were three to five times more likely to demonstrate executive function impairment than all other groups.

There is a lot more research to be done on this topic, but Rubin suggested that the tighter coupling between HIV status and depression in women might actually be a neural manifestation of HIV. The higher prevalence of depression in women living with HIV might in turn explain why these women are most likely to experience executive functioning impairment.

This study did, however, have a number of limitations. First, the WIHS and MACS studies have different durations and collected different data, which made direct comparisons difficult. Both data sets also rely on self-reported measures of depression, which can be inaccurate. And the long-running studies did not collect data on some potential cofactors such as use of antidepressants or mental health services, other medications that might have psychological side effects, or trauma.

Still, Rubin noted, this study shows us why it's critical to consider HIV comorbidities. It was only by looking at depression and cognition together that the research yielded a new sex-specific vulnerability. The key to moving forward, she added, would be more research, including additional imaging studies, to understand the interactions between HIV and mental health and how these influence the neurocircuitry that controls executive function.

In the meantime, the findings indicate that improved access to psychiatric and psychological treatment for depression might help minimize neurocognitive impairment, particularly in women living with HIV.