Resting-state neural signatures of depressive symptoms in acute HIV

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.

Keywords: Acute HIV infection; Amygdala; Anterior cingulate cortex; Depression; Resting-state functional connectivity.

Figure 1.. Differences in rsFC of the amygdala in AHI versus controls.

A. Greater rsFC between the left amygdala and right parahippocampal gyrus in AHI versus control groups; Decreased rsFC (i.e., decreased negative correlations) between the right amygdala and the B. right cerebellum, and C. left cerebellar tonsil in AHI versus control groups. The amygdala seed ROIs (red) and all results were displayed on the group average structural MRI in MNI template space. Bar graphs display the average z-scores for each significant cluster for each group. All results survived whole-brain cluster correction, including Bonferroni-correction for number of ACC seed regions (p_FWE < 0.01, p < 0.001 uncorrected). Color bar depicts the t-statistic from the unpaired two-sample t tests.

Figure 2.. Depressive symptoms are related to distinct patterns of rsFC of sgACC regions in AHI.

A. Depressive symptoms associated with decreased rsFC between anterior subgenual ACC and right precuneus; B. Depressive symptoms associated with increased/decreased rsFC between posterior subgenual ACC and lateral and medial prefrontal, medial and lateral parietal, and cerebellar regions. The sgACC seed ROIs and all results are displayed on the group average structural MRI in MNI template space. All results survived whole-brain cluster correction, including Bonferroni-correction for number of ACC and amygdala seed regions (p_FWE < 0.01, p < 0.001 uncorrected). Color bar indicates uncorrected t values across all findings.

Figure 3.. Depressive symptoms are related to increased and decreased rsFC of amygdala regions in AHI.

A. Depressive symptoms associated with increased rsFC between left amygdala and left fusiform gyrus extending to cerebellum in AHI; B. Depressive symptoms associated with decreased rsFC between left amygdala and right precuneus in AHI. The amygdala seed ROIs and all results are displayed on the group average structural MRI in MNI template space. All results survived whole-brain cluster correction, including Bonferroni-correction for number of ACC and amygdala seed regions (p_FWE < 0.01, p < 0.001 uncorrected). Color bar indicates uncorrected t values across all findings.