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Resting-state neural signatures of depressive symptoms in acute HIV

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Abstract

Depressive symptoms are often elevated in acute and chronic HIV. Previous neuroimaging research identifies abnormalities in emotion-related brain regions in depression without HIV, including the anterior cingulate cortex (ACC) and amygdala. However, no studies have examined the neural signatures of depressive symptoms in acute HIV infection (AHI). Seed-based voxelwise resting-state functional connectivity (rsFC) for affective seed regions of interest (pregenual ACC, subgenual ACC [sgACC], bilateral amygdala) was computed for 74 Thai males with AHI and 30 Thai HIV-uninfected controls. Group analyses compared rsFC of ACC and amygdala seed regions between AHI and uninfected control groups. Within the AHI group, voxelwise regression analyses investigated the relationship between depressive symptoms and rsFC for these affective seed regions. Group analyses revealed alterations in rsFC of the amygdala in AHI versus uninfected controls. Depressive symptoms associated with decreased rsFC between ACC regions and posterior cingulate/precuneus, medial temporal, and lateral parietal regions in AHI. Symptoms of depression also correlated to increased rsFC between ACC regions and lateral prefrontal cortex, sgACC, and cerebellum in AHI. Similar to the ACC, depressive symptoms associated with decreased rsFC between amygdala and precuneus. Of blood biomarkers, only HIV RNA inversely correlated with rsFC between posterior sgACC and left uncus. We found that depressive symptoms in AHI associate with altered rsFC of ACC and amygdala regions previously implicated in depression. Longitudinal research in this cohort will be necessary to determine whether these early alterations in rsFC of affective network regions are related to persistent depressive symptoms after combination antiretroviral therapy.

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Acknowledgments

We thank our study participants and the Government Pharmaceutical Organization, Thailand (GPO), ViiV Healthcare, Gilead and Merck for providing the antiretroviral medications for this study.

Funding

This work was supported by National Institutes of Health grants R01MH113560 (VV and RP), K24MH098759 (VV), R01MH095613 (VV and SS), R01NS084911 (JA and SS), and a cooperative agreement (W81XWH-18-2-0040 and W81XWH-11-0174) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the US Department of Defense (DoD) with supplemental funding from the National Institute of Mental Health.

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Correspondence to Carissa L. Philippi.

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This work was supported by a cooperative agreement (W81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD) or the Henry M. Jackson Foundation for the Advancement of Military Medicine. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or HJF.

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Philippi, C.L., Reyna, L., Nedderman, L. et al. Resting-state neural signatures of depressive symptoms in acute HIV. J. Neurovirol. 26, 226–240 (2020). https://doi.org/10.1007/s13365-020-00826-3

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  • DOI: https://doi.org/10.1007/s13365-020-00826-3

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