Imaging the Role of Inflammation in Mood and Anxiety-related Disorders

Felger, Jennifer C.

doi:10.2174/1570159x15666171123201142

Cited by 301 publications

(237 citation statements)

References 337 publications

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“…Thus, our behavior study demonstrates that chronic HFD feeding might attenuate anxiolytic-like and risk-taking exploratory behavior in mice exposed to early LPS administration. The findings of our previous study and other studies indicate that microglial activation-associated inflammation in the amygdala is involved in the development of anxious and emotional behaviors [37][38][39]. However, in this study, we observed that the reduction in LPS-induced microglial activation in the BLA induced by chronic HFD feeding was correlated with reduced explorative behavior/risk-taking behaviors induced by early LPS administration in HFD-fed mice.…”

Section: Discussioncontrasting

confidence: 83%

Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice

Huang

Chen

Kuo

et al. 2020

Preprint

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Background Consecutive peripheral immune challenges can modulate the responses of brain resident microglia to stimuli. High-fat diet (HFD) intake has been reported to stimulate the activation of astrocytes and microglia in the arcuate nucleus (ARC) of the hypothalamus in obese rodents and humans. However, it is unknown whether intermittent exposure to additional peripheral immune challenge can modify HFD-induced hypothalamic glial activation in obese individuals. Methods In this study, we administered 1 mg/kg LPS (or saline) by intraperitoneal (i.p.) injection to 8-week-old male mice after 1, 2, or 8 weeks of a regular diet (show) or HFD. The level of interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) expression in the plasma and hypothalamic tissue was analyzed 24 h after each LPS injection. The behaviors of the animals in the four groups (the chow-saline, chow-LPS, HFD-saline, and HFD-LPS groups) were examined 5 months after exposure to chow or a HFD. Morphological examination of microglia in related brain regions was also conducted. Results The plasma levels and hypothalamic mRNA levels of IL-1b and TNF-a were significantly upregulated 24 h after the first injection of LPS but not after the second or third injection of LPS. Chow-LPS mice displayed increased exploratory behavior 5 months after feeding. However, this LPS-induced exploratory behavior was inhibited in HFD-fed mice. Chronic HFD feeding for 5 months induced apparent increases in the number and cell body size of microglia, mainly in the ARC, and also increased the size of microglia in the NAc and insula. Moreover, microglial activation in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), insula, and basolateral amygdala (BLA) was observed in chow-LPS mice. However, microglial activation in the analyzed brain regions was suppressed in HFD-LPS mice. Conclusions Altogether, the results indicate that intermittent peripheral challenge with LPS might prime microglia in the ARC and NAc to modify their response to chronic HFD feeding. Alternatively, chronic HFD feeding might mediate microglia in LPS-affected brain regions and subsequently suppress LPS-induced exploratory behavior. Our findings suggest that intermittent acute peripheral immune challenges and chronic HFD intake can cause microglia to modify the microenvironment and further modify animal behaviors.

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Section: Discussioncontrasting

confidence: 83%

Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice

Huang

Chen

Kuo

et al. 2020

Preprint

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“…28 Recent studies report that elevated levels of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF), interferon (IFN) and CRP are associated with the maintenance of fear-and anxiety-based symptoms by affecting the activity and connections in regions of the brain implicated in the etiology, including the amygdala, hippocampus, insula, medial prefrontal cortex, and the anterior cingulate. 29,30 However, the results of our study showed that serum CRP levels did not affect the relationship between serum vitamin D levels and the risk of anxiety symptoms. This lack of association could be due to various reasons.…”

Section: Discussioncontrasting

confidence: 64%

The Relationship between Serum Vitamin D Levels, C-Reactive Protein, and Anxiety Symptoms

Kim

Jeon

Lim

et al. 2020

Psychiatry Investig

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Objective The aim of study is to investigate the relationship between serum vitamin D, c-reactive protein (CRP) levels, and anxiety symptoms.Methods Serum vitamin D and CRP levels of 51,003 Korean adult participants were collected retrospectively. Anxiety symptoms were assessed using the Korean version of Beck Anxiety Inventory. Logistic regression was used to estimate the odds ratio (ORs) of anxiety symptoms by serum vitamin D and CRP levels. The regression was adjusted for covariates, and each model was adjusted mutually for vitamin D and CRP levels.Results Compared with sufficient vitamin D levels (≥20 ng/mL), insufficient (10–19.99 ng/mL) and deficient (<10 ng/mL) vitamin D levels were significantly associated with risk of anxiety symptoms. Also, continuous vitamin D levels were negatively associated with the risk of anxiety symptoms. CRP levels did not affect the relationship between vitamin D levels and risk of anxiety symptoms.Conclusion Insufficient (10–19.99 ng/mL) and deficient (<10 ng/mL) vitamin D levels were significantly associated with risk of anxiety symptoms. After adjusting for CRP levels, the results were not changed, and no evidence of interaction between vitamin D and CRP levels was found. CRP levels did not account for the association between vitamin D levels and risk of anxiety symptoms.

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“…Studies have shown that exposure to chronic inflammation leads to decreased dopamine in the brain of nonhuman primates. 46 Moreover, CRP levels ≥3 mg/mL were associated with decreased connectivity among dopamine-rich reward circuitry in depressed patients as revealed by functional magnetic resonance imaging. 10,45,47 While serotonin is typically thought of as the neurotransmitter most commonly associated with depression, the absence of dopamine and its metabolites led to the depressive symptoms of anhedonia, fatigue, and psychomotor retardation.…”

Section: Discussionmentioning

confidence: 99%

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

McFarland

Shaffer

Breitbart

et al. 2018

Cancer

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BACKGROUND: Depression is highly prevalent in lung cancer. Although there is a known association between inflammation and depression, this relationship has not been examined in patients with lung cancer who undergo treatment with immune and other targeted drug therapies. Peripheral blood C-reactive protein (CRP), a marker of systemic inflammation, may help identify metastatic lung cancer patients with inflammation-associated depression. METHOD: Patients with metastatic lung cancer undergoing treatment were evaluated for depression using the Hospital Anxiety and Depression Scale (HADS). Inflammation (CRP and CRP cutoffs ≥1 and ≥3 mg/mL) and demographic and treatment variables were analyzed for association with depression. RESULTS: One hundred nine consecutive participants exhibited an average plasma CRP concentration of 1.79 mg/mL (median, 0.75 mg/mL [standard deviation, 2.5 mg/mL), and 20.7% had a CRP concentration of ≥3.0 mg/mL; 23.9% met depression screening criteria (HADS ≥8). A log transformation of CRP was significantly correlated with depression severity (r = 0.47, P < .001). CRP was the only covariate to predict depression severity (P = .008) in a multivariate model including lung cancer disease subtype and type of systemic treatment. Receiver operating characteristic analysis indicated that CRP had moderate predictive accuracy in identifying elevated depression (area under the curve = 0.74). A cutoff of CRP ≥3.0 generated high specificity (88%) but identified only 50% of those with elevated depression. CONCLUSION: Elevated CRP is associated with depression in patients with metastatic lung cancer. Thus, CRP may identify a subset of lung cancer patients with inflammation-induced depression and may be useful in predicting response to treatments that target inflammation or its downstream mediators on the brain.

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Imaging the Role of Inflammation in Mood and Anxiety-related Disorders

Cited by 301 publications

References 337 publications

Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice

Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice

The Relationship between Serum Vitamin D Levels, C-Reactive Protein, and Anxiety Symptoms

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

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