Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks.

Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density-a plausible marker of extracellular oedema-and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.

Dysconnectivity of a brain functional network was associated with blood inflammatory markers in depression.

OBJECTIVE: There is increasing evidence for a subgroup of major depressive disorder (MDD) associated with heightened peripheral blood inflammatory markers. In this study, we aimed to understand the mechanistic brain-immune axis in inflammation-linked depression by investigating associations between functional connectivity (FC) of brain networks and peripheral blood immune markers in depression. METHODS: Resting-state functional magnetic resonance imaging (fMRI) and peripheral blood inflammatory markers (C-reactive protein; CRP, interleukin-6; IL-6 and immune cells) were collected on N = 46 healthy controls (HC; CRP ≤ 3 mg/L) and N = 83 cases of depression, stratified further into low CRP cases (loCRP cases; ≤ 3 mg/L; N = 50) and high CRP cases (hiCRP cases; > 3 mg/L; N = 33). In a two-part analysis, network-based statistics (NBS) was firstly used to ascertain whole-brain FC differences in HC vs hiCRP cases. Secondly, we investigated the association between this network of interconnected brain regions and continuous measures of peripheral CRP (N = 83), IL-6 (N = 72), neutrophils and CD4+ T-cells (N = 36) in depression cases only. RESULTS: Case-control NBS testing revealed a single network of abnormally attenuated FC in the high CRP depression cases compared to healthy controls. Connections within this network were mainly between brain regions located in the left insula/frontal operculum and posterior cingulate cortex, which were assigned to ventral attention and default mode canonical fMRI networks respectively. Within-group analysis across all depression cases, secondarily demonstrated that FC within the identified network significantly negatively scaled with CRP, IL-6 and neutrophils. CONCLUSIONS: The findings suggest that inflammation is associated with disruption of functional connectivity within a brain network deemed critical for interoceptive signalling, e.g. accurate communication of peripheral bodily signals such as immune states to the brain, with implications for the pathogenesis of inflammation-linked depression.

Mental health outcomes after SARS-CoV-2 vaccination in the United States: A national cross-sectional study.

BACKGROUND: Worsening of anxiety and depressive symptoms have been widely described during the COVID-19 pandemic. It can be hypothesized that vaccination could link to reduced symptoms of anxiety and/or depression. However, to date, no study has assessed this. This study aims to examine anxiety and depressive symptoms after vaccination in US adults, meanwhile test sociodemographic disparities in these outcomes. METHODS: Data from the January 6-June 7 2021, cross-sectional Household Pulse Survey were analyzed. Using survey-weighted logistic regression, we assessed the relationships between SARS-CoV-2 vaccination and anxiety and/or depressive symptoms, both on overall and sociodemographic subgroups. We controlled for a variety of potential socioeconomic and demographic confounding factors. RESULTS: Of the 453,167 participants studied, 52.2% of the participants had received the COVID-19 vaccine, and 26.5% and 20.3% of the participants reported anxiety and depression, respectively. Compared to those not vaccinated, the vaccinated participants had a 13% lower odds of anxiety (adjusted odds ratio [AOR] = 0.85, 95%CI 0.83-0.90) and 17% lower odds of depression (AOR = 0.83, 95%CI 0.79-0.85). Disparities on the above associations were identified in age, marital status, education level, ethnic/race, and income level, but not on gender. LIMITATIONS: The causal inference was not able to be investigated due to the cross-sectional study design. CONCLUSION: Being vaccinated for SARS-CoV-2 was associated with lower odds of anxiety and/or depressive symptoms. While those more middle-aged or more affluent, were more likely to show these negative associations, the contrary was observed in ethnic minorities and those with lower educational attainment. More strategic and demography-sensitive public health communications could perhaps temper these issues.

Sexually divergent development of depression-related brain networks during healthy human adolescence.

Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more "disruptive" pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression.