Yang Zhang ^1,2 Yihui He ^3,4 Yuan Fang ^1,2 Miaotian Cai ⁵ Guangqiang Sun ^6,7 Rui Wang ^1,2 Jiaxin Zhen ^1,2 Yulin Zhang ⁵ Zhen Li ^1,8* Yundong Ma ^6,7* Tong Zhang ^1,2*

• ¹ Center for Infectious Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
• ² Beijing Institute for Sexually Transmitted Disease Control, Beijing, China
• ³ Postgraduate Union Training Base of Jinzhou Medical University, PLA Rocket Force Characteristic Medical Center, Beijing, China
• ⁴ Department of Neurology, PLA Rocket Force Characteristic Medical Center, Beijing, China
• ⁵ Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China
• ⁶ Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders and National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
• ⁷ Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
• ⁸ Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, Beijing Municipality, China

Background: Depressive disorders are highly prevalent among people with HIV (PWH) and are related to aberrant inflammation and immune responses. However, there is currently a lack of investigation into the neurological, inflammation, endocrine, and immune aspects of HIV-associated depressive disorders (HADD).The study involved 33 HIV-positive men who have sex with men with depressive disorders (HADD group) and 47 without neuropsychiatric disorders (HIV control group). Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and assessments of peripheral blood. Peripheral blood cytokines, plasma concentrations of hormone and neurotrophic factors, and immune cell levels were determined using liquid chip, enzyme-linked immunosorbent assay, and flow cytometry, respectively. The correlation of imaging alterations with clinical variables and peripheral blood indicators was assessed.Results: Compared to the HIV control group, the HADD group exhibited a higher fractional amplitude of low-frequency fluctuations in the left superior parietal gyrus, lower regional homogeneity in the left precentral gyrus, and reduced voxel-wise functional connectivity for the seed region in the right precentral gyrus with clusters in the right cuneus, etc. Furthermore, the HADD group had higher levels of interferon-gamma, a higher frequency of non-classical monocytes, and higher expression levels of perforin and CD38 on specific cells. These imaging results were significantly correlated with peripheral blood indicators and clinical variables.This rs-fMRI study provides considerable evidence for abnormal intrinsic brain activity in people with HADD. Furthermore, our data also indicate the detrimental effects of depression-related inflammation on PWH. Therefore, it is imperative to increase attention to HADD and implement effective preventive interventions accordingly.