Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

BACKGROUND: Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS: This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS: Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (ß = -0.28, p = 0.01) but had no effect on depression severity at follow-up (ß = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (ß = 0.81, p < 0.001; and ß = 0.31, p = 0.001, respectively). CONCLUSIONS: Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

Short communication: Serum levels of brain-derived neurotrophic factor and association with pro-inflammatory cytokines in acute and recovered anorexia nervosa.

Brain-derived neurotrophic factor (BDNF) is a neuroprotective molecule known to be involved in neuroplasticity, learning and memory. Additionally, it may mitigate the effects of inflammation on the brain. There is inconclusive evidence as to whether reductions in BDNF found in AN are related to features associated with the illness such as changes in inflammatory markers and comorbidities, and whether they persist after recovery. This cross-sectional study measured BDNF and 36 inflammatory markers in the serum of individuals recovered from AN (rec-AN; n = 24), with acute AN (n = 56), and healthy controls (n = 51). We (a) compared BDNF concentrations between AN, rec-AN and controls including four pre-determined covariates; (b) assessed the relationship between BDNF and body mass index, eating disorder (ED) psychopathology and depression; and (c) correlated BDNF with inflammatory markers, stratified by group. The AN group showed reductions in BDNF compared to controls and rec-AN. BDNF was negatively associated with depression and ED psychopathology in the whole sample, but not the AN sample. BDNF was positively correlated with three inflammatory markers in the control group (interleukin (IL)-8, Eotaxin-3, tumor necrosis factor (TNF)-α) and negatively correlated with one (IL-16). The only pro-inflammatory marker associated with BDNF in the AN group was TNF-α, and no pro-inflammatory markers were associated with BDNF in the rec-AN group. These results indicate that BDNF serum concentrations may be a state marker of AN. In people with acute AN, BDNF levels seem to be linked to TNF-α signalling. However, BDNF concentrations do not appear to reflect AN symptom severity.

Nutrient Intake and Dietary Inflammatory Potential in Current and Recovered Anorexia Nervosa.

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary Inflammatory Index (DII®) score and collected blood samples to measure serum concentrations of inflammatory markers. In current AN participants, we found lower intake of cholesterol, compared to HCs, and lower consumption of zinc and protein, compared to HC and recovered AN participants. A one-way ANOVA revealed no significant group differences in DII score. Multivariable regression analyses showed that DII scores were significantly associated with tumour necrosis factor (TNF)-α concentrations in our current AN sample. Our findings on nutrient intake are partially consistent with previous research. The lack of group differences in DII score, perhaps suggests that diet is not a key contributor to altered inflammatory marker concentrations in current and recovered AN. Future research would benefit from including larger samples and using multiple 24-h dietary recalls to assess dietary intake.

Reduced MIP-1ß as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa.

Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1ß were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1ß may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.

Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis.

Inhibitors of the IL-6 signaling pathway, such as tocilizumab, are frequently administered for the treatment of immune diseases, e.g., rheumatoid arthritis and multicentric Castleman's disease. The aim of this systematic review and meta-analysis was to ascertain the effects of IL-6 pathway inhibitors on weight and body mass index (BMI). Using PRISMA guidelines, we systematically reviewed relevant articles from three databases (PubMed, OVID, EMBASE). A random effects model was used to estimate standardized mean change (SMCC). Ten studies with a total of 1531 patients were included in the meta-analysis for weight and ten studies with a total of 1537 patients were included in the BMI meta-analysis. The most commonly administered IL-6 pathway inhibitor was tocilizumab. IL-6 pathway inhibitors were associated with increases in weight (SMCC = 0.09, p = 0.016, 95% CI [0.03, 0.14]) and BMI (SMCC = 0.10, p = 0.0001, 95% CI [0.05, 0.15]). These findings suggest that the IL-6 pathway is involved in weight regulation. Modulating IL-6 signaling may be a potential future therapeutic avenue used as an adjunct for the treatment of disorders associated with weight changes, such as cancer cachexia and anorexia nervosa.

Impact of TNF-α Inhibitors on Body Weight and BMI: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis of longitudinal studies was to ascertain to effects of TNF-α inhibitor therapy on body weight and BMI. METHODS: Three databases (PubMed, OVID, and EMBASE) were systematically searched from inception to August 2018. We identified prospective, retrospective, and randomized controlled studies in adults with immune-mediated inflammatory diseases treated with TNF-α inhibitors based on pre-specified inclusion criteria. A random-effects model was used to estimate standardised mean change (SMCC). RESULTS: Twenty-six longitudinal studies with a total of 1,245 participants were included in the meta-analysis. We found evidence for a small increase in body weight (SMCC = 0.24, p = .0006, 95% CI [0.10, 0.37]) and in BMI (SMCC = 0.26, p < .0001, 95% CI [0.13, 0.39]). On average, patients gained 0.90kg (SD = 5.13) under infliximab, 2.34kg (D = 5.65) under etanercept and 2.27kg (SD = 4.69) during treatment with adalimumab within the duration of the respective studies (4-104 weeks). CONCLUSION: Our results yield further support the for the view that TNF-α inhibitors increase body weight and BMI as a potential side effect. Modulating cytokine signaling could be a future therapeutic mechanism to treat disorders associated with weight changes such as anorexia nervosa.

Water supplementation after dehydration improves judgment and decision-making performance.

Previous research has shown that dehydration and water supplementation affect mood and cognitive performance in both adults and children on a variety of tasks that assess memory, attention, executive function, and speeded responses. Given the varied effects of water on cognition, this study explored potential effects of water supplementation, hydration status, and thirst on thinking and decision-making tasks. 29 adult participants undertook a battery of cognitive tests on two separate occasions after having fasted from the previous night. On one occasion, they were offered 500 ml of water to drink prior to testing. Measures of urine osmolality confirmed the group-level effectiveness of the dehydration manipulation. Water supplementation was found to improve performance on tasks measuring cognitive reflection in judgement and decision-making. This increase in performance was associated with differences in tasks implicated in inhibition processes. Drinking water after a 12-h dehydration period increased performance in judgement and decision-making tasks, and this was not explained by differences in subjective thirst or attentiveness.

Cytokine Research in Depression: Principles, Challenges, and Open Questions.

Cytokines have been implicated in the pathology of depression. Currently, the evidence is based on cross-sectional studies and meta-analytic research comparing blood concentrations of T helper type 1 (TH1), T helper type 2 (TH2), pro-inflammatory or anti-inflammatory cytokines of patients with a depressive disorder to those of healthy controls. Additionally, multiple longitudinal studies have investigated cytokine levels during antidepressant treatment. According to the current literature, it seems that peripheral levels of interleukin (IL)-6, IL-10, IL-12, IL-13, and tumor necrosis factor (TNF)-α are elevated and that interferon (IFN)-γ levels are lower in patients with depression compared to healthy controls. However, the overlap of cytokine values between acutely depressed patients, remitted and recovered patients and healthy controls is considerable. Thus, the discriminative power of cytokine concentrations between depressed and non-depressed people is likely weak. Treatment with certain antidepressants appears to decrease peripheral levels of IL-6, IL-10, and TNF-α. However, weight gain-inducing psychopharmacological substances, such as the antidepressant mirtazapine, have been reported to potentially increase the production of pro-inflammatory cytokines. Even though cytokines are often discussed as biomarkers for depression, they have also been shown to be altered in other psychiatric disorders. Moreover, many environmental, social, psychological, biological, and medical factors are also associated with cytokine changes. Thus, cytokine alterations seem extremely unspecific. The interpretation of the results of these studies remains a challenge because it is unknown which type of cells are most responsible for cytokine changes measured in the blood nor have the main target cells or target tissues been identified. The same cytokine can be produced by multiple cell types, and the same cell can produce various cytokines. Additionally, redundancy, synergy, antagonism, and signaling cascades of cytokine signaling must be considered. Cytokines might not be associated with the diagnosis of depression according to the currently used diagnostic manuals, but rather with specific subtypes of depression, or with depressive symptoms across different psychiatric diagnoses. Therefore, the currently available diagnostic systems may not be the ideal starting point for psychiatric cytokine research.