Prolonged confinement in cramped spaces can lead to derangements in brain function/structure, yet the underlying mechanisms remain unclear. To investigate, we subjected mice to restraint stress to simulate long-term narrow and enclosed space confinement, assessing their mental state through behavioral tests. Stressed mice showed reduced center travel and dwell time in the Open Field Test and increased immobility in the Tail Suspension Test. We measured lower hippocampal brain-derived neurotrophic factor levels and cortical monoamine neurotransmitters (5-HT and NE) in the stressed group. Further examination of the body\'s immune levels and serum metabolism revealed immune dysregulation and metabolic imbalance in the stressed group. The results of the metabolic network regulation analysis indicate that the targets affected by these differential metabolites are involved in several metabolic pathways that the metabolites themselves participate in, such as the \"long-term depression\" and \"purine metabolism\" pathways. Additionally, these targets are also associated with numerous immune-related pathways, such as the TNF, NF-κB, and IL-17 signaling pathways, and these findings were validated using GEO dataset analysis. Molecular docking results suggest that differential metabolites may regulate specific immune factors such as TNF-α, IL-1β, and IL-6, and these results were confirmed in experiments. Our research findings suggest that long-term exposure to confined and narrow spaces can lead to the development of psychopathologies, possibly mediated by immune system dysregulation and metabolic disruption.

Previous research has shown a significant association between weight and telomere length, but did not take into consideration weight range. The study was to investigate the association of weight range with telomere length.
Data of 2918 eligible participants aged 25-84 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cycle were analyzed. Information about demographic variables, lifestyle factors, anthropometric variables, and medical comorbidities were included. Univariate and multivariate linear regression model with adjustments for potential confounders were employed to determine the association between weight range and telomere length. A non-parametrically restricted cubic spline model was used to illustrate the possible non-linear relationship.
In univariate linear regression, BMImax, BMI range, and weight range all revealed significant negative associations with telomere length. However, annual rate of BMI/weight range showed a significant positive associations with telomere length. There was no significant association between telomere length and BMImin. After adjusting for potential confounders, the inverse associations persisted in BMImax (β=-0.003, P<0.001), BMI range (β=-0.002, P=0.003), and weight range (β=-0.001, P=0.001). Furthermore, annual rate of BMI range (β=-0.026, P=0.009) and weight range (β=-0.010, P=0.007) presented negative associations with telomere length, after adjusting for covariates in Model 2-4. The association between BMImin (β =-0.002, P=0.237) and telomere length still could not reach statistical significance in multivariate linear regression model. The results of restricted cubic spline analysis showed that BMImax (P for nonlinear =0.026), BMI range (P for nonlinear =0.022), weight range (P for nonlinear =0.035), annual rate of BMI range (P for nonlinear =0.030), and annual rate of weight range (P for nonlinear =0.027) all had nonlinear inverse associations with telomere length.
The study suggests that weight range is inversely associated with telomere length in U.S. adults. Larger weight fluctuation may accelerate telomere shortening and aging.

Background/Objectives - Frailty is highly prevalent with increasing age. Based on the concept of depression as a disorder of accelerated aging and its association with inflammation and metabolic dysregulation, we examined whether frailty measures at baseline and over time differed between immuno-metabolic subtypes of late-life depression. Methods - Clinical cohort study in primary and secondary mental health care with two-year follow-up. In total 359 depressed older patients (≥ 60 years) classified in four immuno-metabolic subgroups by latent profile analysis. We compared frailty measures at baseline and two-year follow-up adjusted for confounders between immuno-metabolic based depressed subgroups. Frailty measures included the frailty index, physical frailty phenotype, and two proxies (handgrip strength, gait speed). Results - At baseline, the relatively healthy depressed subgroup (n = 181) performed best on all frailty markers. While frailty markers worsened over time, the two-year course did not differ between the subgroups for any of these markers. Conclusion - The more severe immuno-metabolic dysregulation present in late-life depression, the more frail. Nonetheless, as trajectories over time did not differ between subgroups, the difference probably emerged at midlife. Future studies should examine whether geriatric assessment might become relevant at earlier ages in specialized mental health care.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction associated with fatty liver disease (MAFLD) recently. We aimed to explore the risk of all-cause deaths in MAFLD participants and compare it with NAFLD in Chinese adults.
METHODS: We enrolled 152,139 participants with abdominal ultrasonography in the Kailuan Cohort from 2006 to 2012. We categorized the participants into MAFLD and non-MAFLD, NAFLD and non-NAFLD, and four groups of Neither-FLD, MAFLD-only, NAFLD-only, and MAFLD-NAFLD, respectively. We used Cox regression models to estimate the hazard ratios and 95% confidence interval (CI) of death.
RESULTS: The prevalence of MAFLD and NAFLD was 31.5% and 27.3%, respectively. After a median follow-up of 12.7 years, MAFLD and NAFLD were both associated with increased mortality, especially in men aged <40, with HR (95% CI) of 1.51(1.19-1.93) and 1.37(1.06-1.78), respectively. The MAFLD-only group had higher mortality than the NAFLD-only in males aged ≥ 60 (adjusted HR=1.43; 95% CI, 1.00-2.03) and lower risk in males aged 40-59 (adjusted HR=0.65; 95% CI,0.48-0.90). MAFLD with overweight/obesity-only decreased, but those with diabetes and/or metabolic dysregulation increased the risk of death. MAFLD with positive HBsAg and/or excessive alcohol consumption further increased the risk of death, especially in men aged <40 years (HR, 9.86; 95% CI, 2.44-39.98).
CONCLUSIONS: MAFLD was associated with increased all-cause mortality among the Chinese population, which was different by the status of overweight/obesity, diabetes, other metabolic indicators, and second causes. MAFLD patients should be managed by metabolic indicators and second causes to fulfill precise treatment and management.

This study aimed to examine how loneliness contributes to metabolic dysregulation among older adults with depression and determine the relative contribution of loneliness to the development of chronic diseases in late adulthood. Harmonised data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project were used. Concretely, the sample comprised 6195 participants (53.95% women; M = 61.30 years, SD = 7.11) from three European cohorts. Three groups were considered: control group (CG); depressive symptom episode group (DEP); and a group with depression and loneliness (DEP + LONE). A metabolic score was estimated using anthropometric and blood indicators, by means of multi-indicator multi-causes (MIMIC) modelling and after controlling for sociodemographic and health-related covariates. Group-comparison was based on measurement-invariance procedures. Multimorbidity development was predicted at follow-up considering the study group and relevant covariates. All the analyses were sex-specific. As a result, measurement invariance revealed the influence of group (ΔCFI = -0.017 for male participants and ΔCFI = -0.009 for female ones) on metabolic scores in both sexes. Metabolic scores were significantly lower (i.e., they had more metabolic risk) in DEP + LONE women in comparison to women from the other groups. DEP men showed the lowest metabolic scores but those from the DEP + LONE group showed meaningfully lower scores than CG men (d = 1.35). In terms of multimorbidity prediction, DEP + LONE group membership significantly predicted the outcome in both sexes; DEP group membership significantly predicted multimorbidity at follow-up in women. In summary, these results highlight the relevant contribution of loneliness in depression-related metabolic dysregulation in the short- (concurrent metabolic risk) and long-term (chronic condition development). Moreover, sex-specific mechanisms seem to be involved in metabolic alterations of depressed people showing loneliness feelings. This study calls for action to reduce the impact of loneliness in old age and to promote healthy ageing.

To investigate the cross-sectional association between depressive symptoms and metabolic risk factors with cognitive function in a middle-aged population.
A stratified subsample of the CARTaGENE (CaG) cohort (n = 1991) was used to compare cognitive function outcomes between groups. The stratification was based on the presence of depressive symptoms and metabolic dysregulation (MetD): the presence of a) neither condition (reference group); b) MetD only; c) depressive symptoms only; and d) both depressive symptoms and MetD. Individuals with type 2 diabetes were excluded. Three cognitive domains were assessed: processing speed, episodic memory, and executive function. An overall cognitive function score, standardized for age and education, was computed. Poor cognitive function was defined as the lower quartile of the overall cognitive function distribution. Linear and logistic regression analyses were conducted.
The poorest cognitive performance was observed in the group with both depressive symptoms and MetD, followed by the group with depressive symptoms only, then the group with MetD only and the reference group. Mean (SD) overall cognition scores for the four groups were -0.25 (1.13), -0.13 (1.05), 0.11 (0.90), and 0.15 (0.93), respectively. Linear regression analyses suggested a linear increase in cognitive function across groups.In the logistic regression analyses, the highest risk of poor cognitive function was observed in the comorbid (depressive symptoms and MetD) group (adjusted OR = 1.99, 95% CI 1.46, 2.71).
Comorbidity of depressive symptoms and MetD was associated with reduced cognitive performance in middle-aged adults without diabetes.KEY POINTSPoor cognitive function is a major public health concern and can be potentially prevented by targeting its modifiable risk factors.Metabolic dysregulation and depression have both been independently associated with poor cognitive function.Comorbidity of metabolic dysregulation and depressive symptoms is associated with an increased risk of poor cognitive function in middle-aged individuals.Future health interventions might benefit by screening for comorbidity in patients with poor cognitive function and by targeting depression and metabolic dysregulation together.

The aim of this study was to investigate the relationship between serum ferritin level and antioxidative status and metabolic dysregulation in young adult obese population. This cross-sectional study included 300 subjects of either sex, grouped as obese and non-obese subjects. The body mass index, total iron binding capacity, fasting blood glucose, superoxide dismutase activity, and levels of serum ferritin, iron, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glutathione, and vitamin C were estimated. Analysis showed a significant alteration in all the parameters in obese adults. The correlation of ferritin level and body mass index showed a positive correlation (r = -0.81, p < 0.001, respectively) with levels of fasting blood glucose, superoxide dismutase, total cholesterol, low-density lipoprotein cholesterol, and triglyceride in obese individuals, whereas an insignificant correlation with vitamin C and glutathione level was observed in obese individuals. The significant positive correlation of ferritin level with the metabolic parameters and some antioxidative parameters in obese individuals signifies the development of metabolic disorders. Therefore, estimation of serum ferritin level will be an important early indicator for the risk of developing metabolic disorders in young adults.

BACKGROUND: Climacteric is associated with both depression and metabolic dysregulation. Scarce evidence suggests that metabolic dysregulation may predict poor response to conventional antidepressants. Response to depression treatment has not been studied in homeopathic medicine. The aim of this study was to investigate the prevalence of metabolic disorders in depressed climacteric women treated with homeopathic medicines, fluoxetine or placebo, and if these alterations have any association with response to depression treatment.
METHODS: One hundred and thirty-three Mexican women (40-65 years) with depression, enrolled in the HOMDEP-MENOP study, a randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a 6 week follow-up, underwent a complete medical history and clinical examination. Metabolic parameters were assessed at baseline. Association between baseline metabolic parameters and response to depression treatment was analyzed with bivariate analysis in the three groups. Odds ratios (OR) with their 95% confidence interval (95% CI) were calculated. Metabolic parameters were considered for inclusion in the logistic regression model if they had a statistically significant relationship with response rate on bivariate analysis at p<0.05 or if they were clinically relevant.
RESULTS: Overall combined prevalence (obesity and overweight) was 86.5%; 52.3% had hypertriglyceridemia; 44.7% hypercholesterolemia; 46.7% insulin resistance; and 16% subclinical hypothyroidism. There was no statistically significant association between dyslipidemia, overweight, or insulin resistance and non-response in the homeopathy group [OR (95% CI) 1.57 (0.46-5.32), p=0.467; 0.37 (0.003-1.11), p=0.059; 0.67 (0.16-2.7), p=0.579, respectively].
CONCLUSIONS: Metabolic dysregulation was not significantly associated with response to depression treatment in depressed climacteric women treated with individualized homeopathic treatment (IHT), fluoxetine or placebo. Due to the high prevalence of metabolic disorders and its relationship with depression in the climacteric, further investigation should be focused on whether individualized prescriptions based on classical homeopathy for depressed climacteric women have an effect on metabolic parameters, and/or if treating the metabolic disorders at the same time could lead to higher response rates. ClinicalTrials.gov Identifier: NCT01635218 URL: http://clinicaltrials.gov/ct2/show/NCT01635218?term=depression+homeopathy&rank=1.