Neuroimmunometabolic alterations and severity of depressive symptoms in people with HIV: An exploratory diffusion-weighted MRS study

Depression is associated with inflammation in the periphery and the central nervous system. People with HIV are at greater risk for depression, which may in part be driven by sustained neuroinflammation, although individuals with severe depression are often excluded from studies of HIV-related co-morbidities. In this exploratory study, we aimed to explore the neuroimaging signatures of severe and persistent depression among people with HIV. We enrolled N = 20 adults with HIV in Brighton, UK, of whom n = 11 had a Patient Health Questionnaire-9 (PHQ-9) score ⩾15 and a history of receiving antidepressant medication. We used diffusion-weighted magnetic resonance spectroscopy (DW-MRS), an emerging neuroimaging technique sensitive to neuroinflammation, to assess neurometabolite diffusion in the anterior cingulate cortex. Participants also underwent standard magnetic resonance spectroscopy (MRS) to assess neurometabolite concentrations in the anterior cingulate cortex, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess blood-brain barrier permeability in the whole brain and the thalamus. We observed a significant positive correlation between intracellular diffusion of creatine and depressive symptom severity (ρ = 0.46, p = 0.047). Increased creatine diffusion has previously been reported in conditions characterised by hypermetabolism and neuroinflammation, suggesting that worse depressive symptom severity in people with HIV may be correlated with neuroimmunometabolic alterations. Metabolite concentrations and blood-brain barrier permeability largely did not correlate with depressive symptom severity in this sample. In summary, we explored neuroimaging signatures of severe depression in people with HIV, including by applying diffusion-weighted magnetic resonance spectroscopy in this population. We report early evidence that worse depressive symptom severity in people with HIV may be correlated with neuroimmunometabolic dysfunction, evidenced by increased diffusion of creatine, likely reflecting hypermetabolism and neuroinflammation. Future research may aim to replicate these findings in larger and more diverse samples and compare the diffusion of neurometabolites between people with and without HIV living with severe depression.