Dietary restriction or exercise regimens can promote weight loss or physical fitness among patients with obesity. However, intervention-associated adverse effects may impede patients' motivation to participate in dietary/exercise interventions. We examined the effects of time restricted eating (TRE) with or without resistance training (RT) on body composition, mood profile, and sleep quality in young college adults with overweight or obesity.

Fifty-four young college students with overweight/obesity were randomized into control (CON), TRE, RT, and TRE plus RT (TRE+RT) trials. The TRE trials restricted to an eating window of 10-hour/day for 8-week. The RT trials performed supervised resistance exercise, while the control trial maintained a regular lifestyle. Changes in body composition variables, blood pressure, mood status, and sleep quality were measured before and after the intervention.

TRE intervention alone or in combination with RT significantly (p < 0.01) decreased body weight (>2 kg) and BMI (~1 kg/m2) in adults with overweight/obesity. Both RT alone and combined with TRE substantially decreased fat mass by 1.1 ± 0.5 and 3.2 ± 0.4 kg, respectively. The decreased fat mass was greater in the combination trial than in the RT trial, whereas TRE alone had no effect. In contrast, fat-free mass was significantly (p < 0.01) decreased with TRE (-2.3 ± 06 kg), increased with RT (1.6 ± 0.3 kg), and was stably maintained with combination interventions. The reduced waist and hip circumferences in the TRE (p < 0.01) were similar to those in the TRE+RT trials, however, RT alone had no effect. Time and group interaction showed a large effect size (partial eta squared) for all body composition variables. In addition, RT with or without TRE notably decreased diastolic blood pressure (RT: -5.5 ± 1.9 mmHg, TRE+RT: -4.1 ± 1.5 mmHg, p < 0.05). Mild anxiety levels at baseline in RT (4.8 ± 2.6) and TRE+RT (4.1 ± 3) trials were found to be normal at postintervention in TRE+RT (3.6 ± 1.7) but not in RT (5.6 ± 3.5). No depression or stress was recorded among the participants during the intervention. The reported poor sleep quality among participants at baseline was significantly improved with RT (4.8 ± 2.9; p < 0.05), and tended to improve with TRE+RT interventions (4.5 ± 1.9).

10-hour TRE is beneficial for weight/fat loss without affecting mood status. However, TRE combined with RT might be more effective for weight/fat loss, maintaining muscle mass, and good quality of sleep among young adults with overweight or obesity.

Intranasal (IN) esketamine was approved as a therapy for treatment-resistant depression in March 2019. There continues to be interest in the field to better understand factors associated with response to treatment. The aim of the current study is to assess the association between BMI and response to esketamine.

A retrospective analysis was conducted on all patients treated with intranasal esketamine at the Yale Interventional Psychiatry Service between January 2015 and May 2023. The primary outcome was the association between BMI (ctegorized as obese vs. non-obese) and response to treatment (≥50 % improvement) by Montgomery-Åsberg Depression Rating Scale (MADRS). Statistical models, including generalized linear mixed-effects models were employed.

A total of 190 patients met criteria for inclusion in the study, out of which 34.2 % were categorized as obese. Patients with obesity were significantly more likely to respond to esketamine treatment (RR = 1.63; p = 0.033) compared to non-obese patients. No linear association between BMI and treatment response was observed when BMI was treated as a continuous variable (RR = 1.02, p = 0.163).

Obesity appears to be associated with a higher response rate to intranasal esketamine treatment for depression. Although the underlying mechanisms of this association are still unknown, increased body fat may prolong the presence of lipid-soluble compounds such as ketamine/esketamine or their active metabolites.

To investigate factors associated with anxiety and depression in perimenopausal women experiencing abnormal uterine bleeding (AUB), with a focus on endocrine markers and lifestyle factors.

This retrospective cohort study analyzed 1,234 perimenopausal women with AUB treated at a tertiary hospital from January 2023 to January 2024. Participants were classified based on DSM-5 diagnoses of anxiety and depression. Data collected included demographics, lifestyle habits, comorbidities, psychiatric history, and endocrine levels (estradiol, follicle-stimulating hormone [FSH], luteinizing hormone [LH], cortisol, prolactin, testosterone, and thyroid-stimulating hormone [TSH]). Logistic regression models identified independent predictors, with interaction and stratified analyses conducted by age group (< 50 and ≥ 50 years).

Factors associated with anxiety and depression included higher BMI (OR 1.08, P = 0.008), longer AUB duration (OR 1.12, P = 0.001), single/divorced/widowed marital status (OR 1.54, P = 0.015), and lower education levels (OR 1.62, P < 0.001). Smoking history (OR 2.84, P < 0.001) and psychiatric history (OR 3.11, P < 0.001) emerged as strong predictors, while regular exercise was protective (OR 0.64, P = 0.001). Hormonal factors, including lower estradiol and elevated levels of FSH, LH, and cortisol, were significantly linked to increased odds of psychological distress (P < 0.01). Interaction analyses revealed that smoking and elevated cortisol exacerbated risks, whereas regular exercise mitigated the adverse effects of elevated FSH and LH. These associations were consistent across age groups.

Anxiety and depression in perimenopausal women with AUB are influenced by a combination of demographic, lifestyle, clinical, and endocrine factors. Addressing modifiable risk factors, such as smoking cessation and increased physical activity, may alleviate psychological distress. Further research is needed to elucidate the hormonal pathways connecting endocrine changes to mental health.

Major depressive disorder (MDD) is prevalent worldwide and impacts the health and quality of life of millions of people. MDD is a condition influenced by a complex interplay of genetic, psychological and environmental factors. This narrative review examines the roles of stress vulnerability, resilience, and lifestyle habits in shaping the risk of depression, emphasizing holistic approaches that address both biological and environmental factors in mental health management. Vulnerability to stress, influenced by factors such as childhood adversity and personality traits such as neuroticism, increases the probability of MDD. On the other hand, resilience acts as a protective mechanism, reducing stress reactivity and supporting mental health. The main findings suggest that healthy lifestyle habits, including consistent sleep patterns, a balanced diet and regular exercise, play significant roles in increasing resilience and preventing depressive symptoms. Interventions to build resilience, such as emotional skills training and promoting a growth mindset, have been proven effective in reducing depressive symptoms. Overall, the findings suggest that lifestyle modifications combined with psychological strategies to build resilience can significantly reduce depressive disorders. This study advocates for personalized therapeutic strategies that consider the multifactorial nature of depressive disorders, integrating psychological and lifestyle interventions to enhance resilience and mental health.

The aim of this study was to evaluate long-term inflammatory, biochemical and behavioral parameters in adult male and female Wistar rats submitted to a model of high-fat and high fructose diet and sepsis. In the study we used 8-month-old male and female rats. High-fat and high fructose diet was provided for 4 months, and sepsis was induced shortly afterwards. Behavioral tests were performed at 10, 30 and 60 days after sepsis induction, at 30- and 60-days metabolic parameters, leptin and cytokines (prefrontal cortex and hippocampus) were determined. High-fat and high-fructose diet was able to induce glucose intolerance. Sepsis favored anxious behavior at 10 days after sepsis, remaining at 30 days and with apparent improvement at 60 days in females and maintenance of behavior in males. Cognitive damage was observed both at 30 and 60 days in animals from both groups. Plasma metabolic parameters were elevated only males exposed to a high-fat high-fructose diet and submitted to CLP only at 30 days. Long-term brain inflammation was not consistently affected both by sex and high-fat and high fructose diet.The relationship between high-fat and high fructose diet, gender and sepsis is still contradictory, as are the mechanisms involved in this paradox. Models and analyses need to be standardized in order to better understand how this event occurs.

Background/Objectives: Obesity and depression, in conjunction with multimorbidity, are interconnected conditions increasingly managed in general practitioner (GP) settings, yet these associations remain insufficiently studied in older patients. This study investigates the prevalence of depression across different body mass index (BMI) classes and includes age and gender differences in multimorbid older patients, offering a novel perspective on subgroup-specific patterns. Further the agreement between GP depression diagnoses and the Geriatric Depression Scale (GDS) is studied and patient-specific factors that may affect the agreement are explored, aiming to improve future diagnostics for vulnerable subgroups. Methods: Data were provided by the baseline assessment of the MultiCare Study, a prospective multicenter observational cohort of multimorbid patients aged 65+ years recruited from 158 GP practices across eight study centers in Germany. Data from 2568 study participants were analyzed based on GP-coded International Classification of Diseases (ICD) diagnoses, structured GP questionnaires, and patient questionnaires. Assessments included data on the BMI and depression (15 item version of the GDS). Agreement between GP diagnoses of depression and GDS assessment was measured using Cohen's kappa. Four logistic regression models were used to examine the effects of patient-specific factors on the agreement of depression diagnosis (match or mismatch). Results: GPs diagnosed depression in 17.3% of cases, compared to the detection of depressive symptoms in 12.4% of the patients by GDS (cut-off ≥ 6 points). The highest prevalence rates were observed in patients with obesity class III (25.0% by GP; 21.7% by GDS). Women were significantly more likely to receive a depression diagnosis by a GP across most BMI classes (except obesity classes II and III). The detection of depressive symptoms by GDS was significantly more prevalent in older multimorbid obese patients (≥75 years), except for patients with obesity class III. The overall agreement between GP diagnosis and GDS assessment was weak (κ = 0.156, p < 0.001). The highest agreement was found for people with obesity class III (κ = 0.256, p < 0.05). Factors associated with a True Positive depression diagnosis (match by both GDS and GP) were female gender (odds ratio (OR) = 1.83, p < 0.05), widowhood (OR = 2.43, p < 0.01), limited daily living skills (OR = 3.14, p < 0.001), and a higher level of education (OR = 2.48, p < 0.01). A significantly lower likelihood of a False Negative depression diagnosis was found for patients with obesity class III. Conclusions: This study highlights the significant prevalence of depression among multimorbid older adults across different BMI classes, particularly in those with obesity class III. The weak diagnostic agreement between GP diagnosis and GDS assessment suggests a need for improved diagnostic practices in primary care. Implementing standardized screening tools and fostering collaboration with mental health specialists could enhance the identification and management of depression in this vulnerable population.

Diabetic depression may be closely related to hippocampal inflammation. We hypothesized that Amomum tsao-ko Crevost et Lemaire (A. tsao-ko) might ameliorate depression-like behavior and glucose intolerance by modulating hippocampal inflammation. UPLC-Q-Exactive-MS/MS was used to identified the constituents in the ethanol extract of A. tsao-ko (EEAT). Then a diabetic depression (DD) model was established and treated for 4 weeks. Depression-like behaviors were assessed using the open field test, sucrose preference test and tail suspension test. The neuronal injury was observed by hematoxylin-eosin staining and Nissl staining. Oral glucose tolerance test, fasting blood glucose, hemoglobin Alc, fasting insulin and homeostasis model assessment of insulin resistance were used to evaluate the effects of EEAT on glucose metabolism. Serum lipids, neurotransmitters, neuroendocrine and inflammation levels were detected by biochemical kits and enzyme-linked immunosorbent assay. Activation of microglia markers was detected by immunofluorescence. Western blotting was used to detect the effect of EEAT on the HMGB1/TLR4/NF-κB protein expression. 48 chemical components were identified from EEAT. Animal experiments showed that EEAT improved the levels of glucose and lipid metabolism, alleviated depression-like behaviors, decreased the level of neurotransmitters and increased the secretion of neuroendocrine-related hormones. The activation of microglia and immunofluorescence intensity of neurogenesis also improved. At the same time, the expression of HMGB1, TLR4 and NF-κB proteins in the inflammatory pathway was also inhibited. EEAT had effects on improving DD symptoms, which may be achieved by down-regulating the HMGB1/TLR4/NF-κB protein expression.

Various research in the past has indicated that the NHHR, which represents the ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI) each act independently as contributors to depression risk. Nonetheless, studies exploring the combination of NHHR with BMI in relation to depression are limited. Consequently, the central aim of this study is investigating the joint and interactive effects of NHHR and BMI on depression risk, as well as the mediating role of NHHR.

Encompassing participants aged 20 years or over, this research incorporated a total of 39,704 individuals from the National Health and Nutrition Examination Survey (NHANES), which covered the period of 2005 to 2023. To analyze the impact of NHHR and its combination with BMI on depression, our analytical approach included multivariate logistic regression, restricted cubic spline modeling, interaction testing and subgroup analyses. Additionally, we studied the joint effects of NHHR and BMI. Finally, we applied a four-way decomposition analysis method to examine the interactions and mediating effects within the aforementioned relationships.

Among all participants in this study, the prevalence of depressive disorder (Patient Health Questionnaire-9 score ≥ 10) was 9.2%. Both the NHHR and BMI were associated with depression, which remained significant even after full adjustment for covariates [NHHR, OR (95% CI): 1.07 (1.04-1.09); BMI, OR (95% CI): 1.02 (1.02-1.03)]. Compared with the reference group, the OR (95% CI) for the highest groups of NHHR, BMI, and their product term NHHR-BMI were 1.41 (1.24-1.61), 1.35 (1.18-1.54), and 1.59 (1.37-1.84), respectively. Participants with NHHR in the fourth quartile and BMI exceeding 30 kg/m², had higher depression risk compared to other participants with NHHR in the first quartile and BMI below 25 kg/m² [OR (95% CI): 1.64 (1.34-2.00)]. Results of the four-way decomposition analyses indicated that NHHR played a mediating role in the association between BMI and depression, with the mediating effect accounting for 17.6%. Similarly, NHHR also mediated 11.0% of the mediating effect between BMI and PHQ-9 score. However, no interaction between NHHR and BMI related to depression was found in the general population. After stratifying by gender, it was found that the mediated interaction between NHHR and BMI had a statistically significant effect on depression and PHQ-9 score in males.

Depression risk is linked to both NHHR and BMI, and NHHR has a significant mediating impact on the association between BMI and depression. Notably, there is a non-negligible mediated interaction effect between BMI and NHHR in male participants. Compared to considering NHHR or BMI individually, participants had a higher risk of depression when the combined terms of the two were in the higher quartiles. These findings suggest that the combined assessment of these two indicators may help deepen the understanding and evaluation of depression, enhance the accuracy of risk stratification, and is worthy of further research.

Bidirectional communication between the brain and gastrointestinal tract, called the gut-brain axis, is linked with our emotions. Intestinal lipids, hormones, and molecules, such as bile acids (BAs), impact our mood, motivation, and emotions via the gut-brain axis. BAs are synthesized from cholesterol in the liver and serve as a regulator of lipid metabolism and hormonal secretion in the intestine. Human studies have indicated that the alteration of plasma BA levels is associated with depression and anxiety. Several possible mechanisms, such as BA receptor-dependent and receptor-independent mechanisms, have been reported for emotional control. Animal studies have indicated that the deletion of BA receptors shows behavioral abnormalities. BAs regulate gut hormones, glucagon-like peptide-1 secretion, bioactive lipids, oleoylethanolamide, and the immune system function, which influences neural activities. Thus, BAs act as an emotional regulator. This review aims to summarize the following: clinical evidence of BA concentration linked to mental disorders, including depression and anxiety; and animal studies of BA-related signaling correlated with its neurobehavioral effect supporting its mechanism. We will also discuss future research required for further neurobehavioral treatment.

Youth obesity and depression are public health concerns. Although meta-analyses suggest a positive association between those conditions in adults and adolescents, evidence remains unclear in prepubertal children. We examined the bidirectional associations between levels of depressive symptoms and weight status in 8-10-year-old children with a parental history of obesity, over two years, and whether they differ by sex.

Data were drawn from the QUebec Adipose and Lifestyle InvesTigation in Youth Cohort Study's baseline and first follow-up evaluations (n = 558). Depressive symptoms were assessed using the 12-item Center for Epidemiological Studies Depression scale and weight status using body mass index z-scores based on World Health Organization standards. Linear and logistic regression models were used to test the directionality and magnitude of the associations, adjusting for age, sex, physical activity, screen time, parental education, alcohol and cigarette use, and baseline outcome measure.

Children with higher levels of depressive symptoms at baseline were not more likely to have overweight/obesity at follow-up (odds ratio [95 % Coefficient Interval] = 0.95[0.88;1.02]). Baseline overweight/obesity was not associated with subsequent higher levels of depressive symptoms (beta coefficient [95 % Coefficient Interval] = 0.20 [-0.47;0.87]). No sex differences emerged.

Selection bias may have occurred due to loss at follow-up (10 % attrition) and exclusion of 6 participants taking mood disorder medication.

Unlike in adults and adolescents, no association between weight status and depressive symptoms was observed in childhood over two years. Underlying mechanisms linking both conditions later in life may not apply as early as prepubertal childhood.

Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. We used support-vector machines and whole-brain voxel-wise grey matter volume to generate and validate a BMI predictor in healthy individuals (N = 1504) and applied it to individuals with schizophrenia (SCZ,N = 146), clinical high-risk states for psychosis (CHR,N = 213) and recent-onset depression (ROD,N = 200). We computed BMIgap (BMIpredicted-BMImeasured), interrogated its brain-level overlaps with SCZ and explored whether BMIgap predicted weight gain at 1- and 2-year follow-up. SCZ (BMIgap = 1.05kg/m2) and CHR individuals (BMIgap = 0.51 kg/m2) showed increased and ROD individuals (BMIgap=-0.82 kg/m2) decreased BMIgap. Shared brain patterns of BMI and SCZ were linked to illness duration, disease onset, and hospitalization frequency. Higher BMIgap predicted future weight gain, particularly in younger ROD individuals, and at 2-year follow-up. Therefore, we propose BMIgap as a potential brain-derived measure to stratify at-risk individuals and deliver tailored interventions for better metabolic risk control.

Obesity has become a global epidemic and is associated with comorbidities, including diabetes, cardiovascular, and neurodegenerative diseases, among others. While appreciable insight has been gained into the mechanisms of obesity-associated comorbidities, effects of age, and duration of obesity on the female brain remain obscure. To address this gap, adolescent and mature adult female mice were subjected to a high-fat diet (HFD) for 13 or 26 weeks, whereas age-matched controls were fed a standard diet. Subsequently, the expression of inflammatory cytokines, neurotrophic/neuroprotective factors, and markers of microgliosis and astrogliosis were analyzed in the hypothalamus, hippocampus, and cerebral cortex, along with inflammation in visceral adipose tissue. HFD led to a typical obese phenotype in all groups independent of age and duration of HFD. However, the intermediate duration of obesity induced a limited inflammatory response in adolescent females' hypothalamus while the hippocampus, cerebral cortex, and visceral adipose tissue remained unaffected. In contrast, the prolonged duration of obesity resulted in inflammation in all three brain regions and visceral adipose tissue along with upregulation of microgliosis/astrogliosis and suppression of neurotrophic/neuroprotective factors in all brain regions, denoting the duration of obesity as a critical risk factor for neurodegenerative diseases. Importantly, when female mice were older (i.e., mature adult), even the intermediate duration of obesity induced similar adverse effects in all brain regions. Taken together, our findings suggest that (1) both age and duration of obesity have a significant impact on obesity-associated comorbidities and (2) early interventions to end obesity are critical to preserving brain health.

Obesity is a consequence of multiple factors, including genetics, lifestyle and nutritional choices, physical activity, sleep duration, screen time, and mood disorders. These behavioral elements can impair the regulation of energy balance and obesity management that link obesity to a constellation of chronic conditions that lead to a high prevalence of cardiometabolic risk factors, metabolic syndrome, and nonalcoholic fatty liver disease. Multidisciplinary therapy is defined as an approach delivered by a multidisciplinary-trained health team covering at least two components of behavior, physical activity/exercise, dietary habits, and/or psychological counseling associated with clinical interventions. This narrative review summarizes the effects of multidisciplinary therapy on neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, metabolic syndrome, nonalcoholic fatty liver diseases, behavior, and quality of life. We found that multidisciplinary therapy, including medical, nutritional, exercise, and behavioral counseling, and/or education, was useful for addressing outcomes such as visceral adiposity, neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, nonalcoholic fatty liver disease, and metabolic syndrome. The effects were mediated by improvements in neuroendocrine regulation of energy balance, downregulation of the pro-inflammatory states, and a reduction in comorbidities. Multidisciplinary therapy also improved mood disorders and quality of life.

Polycystic ovary syndrome (PCOS) is a common gynaecological problem for women of reproductive age. Depression and anxiety are common conditions that occur in women with PCOS and have an impact on mental well-being. However, there is a lack of data on their prevalence and its associated factors in the Thai population. This cross-sectional study aimed to evaluate the prevalence of depression and anxiety among women with PCOS and identify the factors associated with depression and anxiety in women with PCOS as well as their impact on mental well-being in Thailand.

A total of 260 women aged 15 to 40 years diagnosed with PCOS based on the Rotterdam criteria were included in the study. Physical examinations were conducted, and participants completed Hospital Anxiety and Depression Scale (HADS) and Thai version WHO-Five Well-Being Index (WHO-5 Thai) questionnaires to assess depression, anxiety, and mental well-being, respectively. The prevalence and prevalence rations (PR) with 95% confidence interval (CI) for depression and anxiety were analysed using modified Poisson regression analyses with robust variance estimators.

The prevalence of depression, anxiety, and poor mental well-being among women with PCOS was found to be 3.85%, 11.92%, and 16.92%, respectively. Abdominal obesity (PR 24.25, 95% CI: 2.75-219.50; p = 0.004), poor mental well-being (PR 16.68, 95% CI: 4.02-69.18; p = < 0.001), and snoring (PR 10.26, 95% CI: 2.06-51.14; p = 0.005) were identified as factors associated with depression in women with PCOS. Having children (PR 6.22, 95% CI: 2.90-13.35; p = < 0.001), alcohol drinking (PR 3.41, 95% CI: 1.52-7.65; p = 0.003), poor mental well-being (PR 2.32, 95% CI: 1.14-4.74; p = 0.021), and hirsutism (PR 2.23, 95% CI: 1.18-4.22; p = 0.014) were found to be relative factors for anxiety in women with PCOS.

Women with PCOS is associated with high prevalences of depression and anxiety. Poor mental well-being was identified as key factors associated with both depression and anxiety in women with PCOS. Based on these findings, the present study suggests that screening for depression and anxiety should be conducted for all women with PCOS, especially those who present with poor mental well-being.

Type 2 diabetes (T2D) is a metabolic disease of major public health concern. It impacts peripheral tissues and the central nervous system, leading to systemic dysmetabolism and neurocognitive impairments, including memory deficits, anxiety, and depression. The metabolic determinants of these neurocognitive impairments remain unidentified. Here, we sought to address this question by developing a proprietary (P-) high-fat diet (HFD), in which glucose intolerance precedes weight gain and insulin resistance.

The P-HFD model was nutritionally characterized, and tested in vivo in mice that underwent behavioral and metabolic testing. The diet was benchmarked against reference models. .

P-HFD has 42% kcal from fat, high monounsaturated/polyunsaturated fatty acid ratio, and 10% (w/v) sucrose in drinking water. When administered, from the early stages of glucose intolerance alone, animals exhibit anxiety-like behavior, without depression nor recognition memory deficits. Long-term P-HFD feeding leads to weight gain, brain glucose hypometabolism as well as impaired recognition memory. Using an established genetic model of T2D (db/db) and of diet-induced obesity (60% kcal from fat) we show that additional insulin resistance and obesity are associated with depressive-like behaviors and recognition memory deficits.

Our findings demonstrate that glucose intolerance alone can elicit anxiety-like behavior. Through this study, we also provide a novel nutritional model (P-HFD) to characterize the discrete effects of glucose intolerance on cognition, behavior, and the physiology of metabolic disease.

Depression is linked to obesity. The body roundness index (BRI) provides a more accurate assessment of body and visceral fat levels than the body mass index or waist circumference. However, the association between BRI and depression is unclear. Therefore, we investigated this relationship using the National Health and Nutrition Examination Survey (NHANES) database.

In this population-based cross-sectional study, data from 18,654 adults aged ≥20 years from the NHANES 2011-2018 were analyzed. Covariates, including age, gender, race/ethnicity, education level, marital status, poverty-income ratio, alcohol status, smoking status, hypertension, diabetes mellitus, cardiovascular disease, energy intake, physical activity, total cholesterol, and triglycerides were adjusted in multivariable logistic regression models. In addition, smooth curve fitting, subgroup analysis, and interaction testing were conducted.

After adjusting for covariates, BRI was positively correlated with depression. For each one-unit increase in BRI, the prevalence of depression increased by 8 % (odds ratio = 1.08, 95 % confidence interval = 1.05-1.10, P < 0.001).

As this was a cross-sectional study, we could not determine a causal relationship between BRI and depression. Patients with depression in this study were not clinically diagnosed with major depressive disorder.

BRI levels were positively related to an increased prevalence of depression in American adults. BRI may serve as a simple anthropometric index to predict depression.

Background: Although Calorie Restriction (CR) is primarily considered in obesity management, behavioral studies of CR and its methodology of implementation are not well-defined. Objective: The study aimed to determine the efficacy of the extensively researched method of CR-abrupt calorie restriction (ACR) and a newly proposed gradual calorie restriction (GCR) in terms of body weight, behavioral and biochemical parameters in the obese animal model-C57BL/6J mice. Design: Male obese mice were subjected to GCR regimen for 14 weeks which was compared and evaluated for anxiety-like behavior and stress levels with ACR. Plasma corticosterone was measured before initiation of CR and every three weeks following GCR and ACR, whereas plasma insulin was measured twice-after obesity induction and post 14 weeks of CR. The behavioral assessments were conducted before inducing CR and every three weeks following ACR and GCR. Results: A significant anxiety-like behavior and an increase in plasma corticosterone were observed in mice on GCR during the critical initial six weeks of CR (p < 0.05). Both groups showed a decrease in plasma glucose levels; however, the GCR group showed a significant reduction (p < 0.01). There was a significant decrease in social interaction in both groups with an increase in the latency period and a decrease in time spent with the stranger animal during the social interaction test (p < 0.05). Conclusion: The mice on GCR regimen demonstrated lesser anxiety-like behavior and low plasma corticosterone levels compared to those on ACR. This gives us a new avenue in CR research to evaluate the methodologies of implementing CR.

The last decade has seen the increased prevalence of obesity as a public health challenge, particularly in low- and middle-income countries. At the same time, studies have shown that there is a two-way relationship between low-calorie diets and depression in obese individuals. This study was designed and implemented to investigate the effect of a low-calorie high-protein diet on psychometric variables in obese individuals.

The present study is a Randomized Clinical Trial. Individuals meeting the inclusion criteria were randomly assigned to either the intervention group (low-calorie diet with increased protein percentage) or the control group (standard protein percentage) using block stratification. Psychometric characteristics of the participants were evaluated using the DASS-21 questionnaire.

There were no significant differences in enrollment between the two groups with respect to anthropometric variables, body composition, and physical activity (p-value > .05). Similarly, no significant differences were observed between the two groups in terms of psychological variables (depression, anxiety and stress) (p-value > .05). However, the intervention groups had significantly lower depression and anxiety scores 15 days into the intervention (p-value < .05). After 30 and 60 days of intervention, significant differences were observed between the 2 groups in terms of depression, stress, and anxiety (p-value < .05), indicating a relative improvement in psychometric variables in the intervention group (p-value < .05).

The results of this study showed that low-calorie diets with a high-protein percentage can significantly improve psychometric variables in obese people.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20221101056371N1..

Excess Food Energy Intake (EFEI), namely Metabolic Food Waste (MFW) corresponds to excess calorie intake related to overconsumption of food and is responsible for overweight (OW) and obesity (OB) conditions. Identifying its causes and impacts could be important, so that it can be prevented and reduced, generating health, environmental and societal benefits. Therefore, this research quantifies MFW among OW and OB adult populations (18-75 years) in Italy and its environmental and social implications. Life cycle assessment (LCA) through the Simapro 9.5 software was used and then, the results were monetized according to the Environmental Price Handbook to understand the real environmental cost. Finally, Social LCA (S-LCA) was considered following the Product Social Impact Assessment (PSILCA) guidelines to understand the potential social risks behind the food that ends up on our plates. The results highlight the amount of MFW in Italy is 2696 billion kcal/year corresponding to 1.59 Mtons over-consumed food/year, while the impacts are mainly related to global warming (8.78 Mtons CO2 eq/year, or 2.29 % of the total Italian CO2 emissions), terrestrial ecotoxicity (843,451 tons 1.4-DCB/year), freshwater ecotoxicity (222,483 tons 1.4 DCB eq/year), and land consumption (8 million m2a eq/year), mostly due to the meat, fats and oils and sweets overconsumption. Impacts monetization also shows that MFW could induce an environmental price of € 1340/per capita/year, and finally, the S-LCA reveals how overconsumption of food has the potential to affect gender discrimination, water depletion, trade union, and social discrimination due to the high proportion of labor migrants in the agricultural sector.

Current evidence implicates a significant association between depression and obesity and related metabolic dysfunction. The weight-adjusted-waist index (WWI) was recently identified as an ideal index that integrates total body fat, muscle mass, and bone mass. This study investigated the relationship between WWI and depressive symptoms in adults.

Participants from the National Health and Nutrition Examination Survey (2005-2018) were enrolled. Depressive symptom severity was measured with the Patient Health Questionnaire-9 (PHQ-9). Survey-weighted multivariable logistic regression, subgroup analysis, and generalized additive models were used to determine the relationship between WWI and depressive symptoms.

A total of 34,575 participants were included, with a mean WWI of 11.01; 2,979 participants were suspected of having depressive symptoms (PHQ-9 score ≥ 10). A significant positive association was identified between WWI and depressive symptoms (odds ratio = 1.416, 95 % confidence interval: 1.303-1.539, P < 0.0001). Subgroup analyses suggested that the association between WWI and depressive symptoms was stronger in individuals who were female, overweight, divorced, middle-aged or older (over 40 years old), and had diabetes. Furthermore, the non-linear multivariable regression revealed an inflection point for the WWI at 11.438, and the association was only significant when the WWI was higher than this point.

This study was retrospective and only included participants from the United States; therefore, further validation is needed from studies in other countries, especially middle-to-low-income countries, using longitudinal cohorts.

This study identified a significant positive association between WWI and depressive symptoms.

To investigate high-risk sociodemographic and environmental determinants of health (SEDH) potentially associated with adult obesity in counties in the United States using machine-learning techniques.

We performed a cross-sectional analysis of county-level adult obesity prevalence (body mass index ≥30 kg/m2) in the United States using data from the Diabetes Surveillance System 2017. We harvested 49 county-level SEDH factors that were used in a classification and regression trees (CART) model to identify county-level clusters. The CART model was validated using a 'hold-out' set of counties and variable importance was evaluated using Random Forest.

Overall, we analysed 2752 counties in the United States, identifying a national median (interquartile range) obesity prevalence of 34.1% (30.2%, 37.7%). The CART method identified 11 clusters with a 60.8% relative increase in prevalence across the spectrum. Additionally, seven key SEDH variables were identified by CART to guide the categorization of clusters, including Physically Inactive (%), Diabetes (%), Severe Housing Problems (%), Food Insecurity (%), Uninsured (%), Population over 65 years (%) and Non-Hispanic Black (%).

There is significant county-level geographical variation in obesity prevalence in the United States, which can in part be explained by complex SEDH factors. The use of machine-learning techniques to analyse these factors can provide valuable insights into the importance of these upstream determinants of obesity and, therefore, aid in the development of geo-specific strategic interventions and optimize resource allocation to help battle the obesity pandemic.

To explore the combined effect of abdominal obesity and depressive symptoms on the risk to type 2 diabetes, while also assessing the potential influence of various glycemic states and gender on this combined relationship.

Data is acquired from the China Health and Retirement Longitudinal Study, and 5949 participants were included for analysis. Participants were divided into four groups: neither have abdominal obesity nor depressive symptoms (AO-/DS-), only have depressive symptoms (AO-/DS+), only have abdominal obesity (AO+/DS-), and have both abdominal obesity and depressive symptoms (AO+/DS+). Stratified analyses differentiating the glycemic statuses and sex of the participants were also carried out.

After adjusting for the confounders, the AO-/DS+, AO+/DS- and AO+/DS+ phenotypes were all discovered to be risk factors for type 2 diabetes (OR = 1.38, 95%CI: 1.06-1.79; OR = 2.07, 95%CI: 1.63-2.63; OR = 2.38, 95%CI: 1.83-3.11, respectively) compared with the AO-/DS- phenotype in the overall population. In further stratified analyses, we arrived at the same conclusion for normoglycemic individuals, especially in females. For prediabetes and males, the AO+/DS- and AO+/DS+ phenotypes are risk factors for type 2 diabetes compared with the AO-/DS- phenotype, but not with AO-/DS+.

Regardless of glycemic status and sex, the coexistence of abdominal obesity and depressive symptoms were associated with an increased risk of type 2 diabetes. Depressive symptoms were independent risk factors for type 2 diabetes only in normoglycemic individuals and females.

The association between obesity and depression may partly depend on the contextual metabolic health. The effect of change in metabolic health status over time on subsequent depression risk remains unclear. We aimed to assess the prospective association between metabolic health and its change over time and the risk of depression across body mass index (BMI) categories.

Based on a nationally representative cohort, we included participants enrolled at the wave 2 (2004-2005) of the English Longitudinal Study of Ageing and with follow-up for depression at wave 8 (2016-2017). Participants were cross-classified by BMI categories and metabolic health (defined by the absence of hypertension, diabetes, and hypercholesterolemia) at baseline or its change over time (during waves 3-6). Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of depression at follow-up stratified by BMI category and metabolic health status with adjustment for potential confounders.

The risk of depression was increased for participants with metabolically healthy obesity compared with healthy nonobese participants, and the risk was highest for those with metabolically unhealthy obesity (OR 1.62, 95% CI 1.18-2.20). Particularly hypertension and diabetes contribute most to the increased risk. The majority of metabolically healthy participants converted to unhealthy metabolic phenotype (50.1% of those with obesity over 8 years), which was associated with an increased risk of depression. Participants who maintained metabolically healthy obesity were still at higher risk (1.99, 1.33-2.72), with the highest risk observed for those with stable unhealthy metabolic phenotypes.

Obesity remains a risk factor for depression, independent of whether other metabolic risk factors are present or whether participants convert to unhealthy metabolic phenotypes over time. Long-term maintenance of metabolic health and healthy body weight may be beneficial for the population mental well-being.

Psychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.

Between 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.

A total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.

The observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

Nervous system processes, including cognition and affective state, fundamentally rely on mitochondria. Impaired mitochondrial function is evident in major depressive disorder (MDD), reflecting cumulative detrimental influences of both extrinsic and intrinsic stressors, genetic predisposition, and mutation. Glucocorticoid 'stress' pathways converge on mitochondria; oxidative and nitrosative stresses in MDD are largely mitochondrial in origin; both initiate cascades promoting mitochondrial DNA (mtDNA) damage with disruptions to mitochondrial biogenesis and tryptophan catabolism. Mitochondrial dysfunction facilitates proinflammatory dysbiosis while directly triggering immuno-inflammatory activation via released mtDNA, mitochondrial lipids and mitochondria associated membranes (MAMs), further disrupting mitochondrial function and mitochondrial quality control, promoting the accumulation of abnormal mitochondria (confirmed in autopsy studies). Established and putative mechanisms highlight a mitochondrial nexus within the psycho-immune neuroendocrine (PINE) network implicated in MDD. Whether lowering neuronal resilience and thresholds for disease, or linking mechanistic nodes within the MDD pathogenic network, impaired mitochondrial function emerges as an important risk, a functional biomarker, providing a therapeutic target in MDD. Several treatment modalities have been demonstrated to reset mitochondrial function, which could benefit those with MDD.

Depression is among the main causes of disability, and its protracted manifestations could make it even harder to treat metabolic diseases. Obesity is linked to episodes of depression, which is closely correlated to abdominal adiposity and impaired food quality. The present review is aimed at studying possible links between obesity and depression along with targets to disrupt it. Research output in Pubmed and Scopus were referred for writing this manuscript. Obesity and depression are related, with the greater propensity of depressed people to gain weight, resulting in poor dietary decisions and a sedentary lifestyle. Adipokines, which include adiponectin, resistin, and leptin are secretory products of the adipose tissue. These adipokines are now being studied to learn more about the connection underlying obesity and depression. Ghrelin, a gut hormone, controls both obesity and depression. Additionally, elevated ghrelin levels result in anxiolytic and antidepressant-like effects. The gut microbiota influences the metabolic functionalities of a person, like caloric processing from indigestible nutritional compounds and storage in fatty tissue, that exposes an individual to obesity, and gut microorganisms might connect to the CNS through interconnecting pathways, including neurological, endocrine, and immunological signalling systems. The alteration of brain activity caused by gut bacteria has been related to depressive episodes. Monoamines, including dopamine, serotonin, and norepinephrine, have been widely believed to have a function in emotions and appetite control. Emotional signals stimulate arcuate neurons in the hypothalamus that are directly implicated in mood regulation and eating. The peptide hormone GLP-1(glucagon-like peptide- 1) seems to have a beneficial role as a medical regulator of defective neuroinflammation, neurogenesis, synaptic dysfunction, and neurotransmitter secretion discrepancy in the depressive brain. The gut microbiota might have its action in mood and cognition regulation, in addition to its traditional involvement in GI function regulation. This review addressed the concept that obesity-related low-grade mild inflammation in the brain contributes to chronic depression and cognitive impairments.

Research in the field of pharmacology aims to generate new treatments for pathologies. Nowadays, there are an increased number of chronic disorders that severely and durably handicap many patients. Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people. For years, these pathologies have been so frequently observed in the population in a concomitant way that they are considered as comorbidities. In fact, common mechanisms are certainly at work in the etiology of these pathologies. The main purpose of this review is to show the value of anticipating the effect of baseline treatment of a condition on its comorbidity in order to obtain concomitant positive actions. One of the implications would be that by understanding and targeting shared molecular mechanisms underlying these conditions, it may be possible to tailor drugs that address both simultaneously. To this end, we firstly remind readers of the close link existing between depression and diabetes and secondly address the potential benefit of the pleiotropic actions of two major active molecules used to treat central and peripheral disorders, first a serotonin reuptake inhibitor (Prozac ®) and then GLP-1R agonists. In the second part, by discussing the therapeutic potential of new experimental antidepressant molecules, we will support the concept that a better understanding of the intracellular signaling pathways targeted by pharmacological agents could lead to future synergistic treatments targeting solely positive effects for comorbidities.

In a large multisite cohort of Veterans who underwent Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy, we compared the 5-year suicidal ideation and attempt rates with matched nonsurgical controls.

Bariatric surgery has significant health benefits but has also been associated with adverse mental health outcomes.

Five-year rates of suicidal ideation and suicide attempts of Veterans who underwent Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy from the fiscal year 2000-2016 to matched nonsurgical controls using sequential stratification using cumulative incidence functions (ideation cohort: n=38,199; attempt cohort: n=38,661 after excluding patients with past-year outcome events). Adjusted differences in suicidal ideation and suicide attempts were estimated using a Cox regression with a robust sandwich variance estimator.

In the matched cohorts for suicidal ideation analyses, the mean age was 53.47 years and the majority were males (78.7%) and White (77.7%). Over 40% were treated for depression (41.8%), had a nonrecent depression diagnosis (40.9%), and 4.1% had past suicidal ideation or suicide attempts >1 year before index. Characteristics of the suicide attempt cohort were similar. Regression results found that risk of suicidal ideation was significantly higher for surgical patients (adjusted hazard ratio=1.21, 95% CI: 1.03-1.41), as was risk of suicide attempt (adjusted hazard ratio=1.62, 95% CI: 1.22-2.15).

Bariatric surgery appears to be associated with a greater risk of suicidal ideation and attempts than nonsurgical treatment of patients with severe obesity, suggesting that patients need careful monitoring for suicidal ideation and additional psychological support after bariatric surgery.

Civilization diseases are defined as non-communicable diseases that affect a large part of the population. Examples of such diseases are depression and cardiovascular disease. Importantly, the World Health Organization warns against an increase in both of these. This narrative review aims to summarize the available information on measurable risk factors for CVD and depression based on the existing literature. The paper reviews the epidemiology and main risk factors for the coexistence of depression and cardiovascular disease. The authors emphasize that there is evidence of a link between depression and cardiovascular disease. Here, we highlight common risk factors for depression and cardiovascular disease, including obesity, diabetes, and physical inactivity, as well as the importance of the prevention and treatment of CVD in preventing depression and other mental disorders. Conversely, effective treatment of CVD can also help prevent depression and improve mental health outcomes. It seems advisable to introduce screening tests for depression in patients treated for cardiac reasons. Importantly, in patients treated for mood disorders, it is worth controlling CVD risk factors, for example, by checking blood pressure and pulse during routine visits. It is also worth paying attention to the mental condition of patients with CVD. This study underlines the importance of interdisciplinary co-operation.

COVID-19 is an ongoing global crisis, with a multitude of factors that affect mental health worldwide. We explored potential predictors for the emergence and maintenance of depression, anxiety, and posttraumatic stress symptoms (PTSS) in the general population in Israel.

Across the span of 16 months, 2478 people completed a repeated self-report survey which inquired psychiatric symptoms and pandemic related stress factors (PRSF). We applied mixed-effects models to assess how each stressor contributes to depression, anxiety and PTSS at each time point, and longitudinally assessed participants who completed at least two consecutive surveys (n = 400). We weighted our sample to increase representativeness of the population.

Fatigue was the strongest predictor for depression, anxiety and PTSS at all time points, and predicted deterioration overtime. Financial concerns associated with depression and anxiety at all time points, and with their deterioration overtime. Health related concerns were uniquely associated with anxiety and PTSS at all time points and their deterioration, but not with depression. Improvement in sense of protection overtime associated with decrease in depression and anxiety. Hesitancy towards vaccination was associated to higher financial concerns and lower sense of protection by the authorities.

Our findings accentuate the multitude of risk factors for psychiatric morbidity during COVID-19, and the centrality of fatigue in determining mental health outcomes.

Bangpungtongsung-san (BTS) is a representative herbal medicine that has been widely used for patients with obesity in east Asian countries. Various preclinical studies have demonstrated the anti-depressive effect of BTS granules in various animal models of depression. This phase II trial aimed to explore the efficacy and safety of BTS in human patients with depression.

A total of 126 patients diagnosed with major depressive disorder and who are not underweight (body mass index ≥ 18.5 kg/m²) will be enrolled in this study. Eligible participants will be randomly allocated into three groups: the high-dose BTS, low-dose BTS, and placebo groups in a 1:1:1 ratio. BTS or placebo granules will be orally administered twice a day for 8 weeks. The BTS and placebo granules will be made to have identical color, scent, and shape, and participants and investigators will be blinded to the allocation. The primary efficacy endpoint is the change from baseline of the 17-item Hamilton Depression Rating Scale total score at 8 weeks. The superiority of the high- and low-dose BTS granules to the placebo granules will be tested.

The results of this clinical trial will provide evidence on the efficacy and safety of BTS for patients with major depressive disorder. This study will be conducted in accordance with ethical and regulatory guidelines, and the results will be submitted and published in international peer-reviewed journals.

CRIS registration Number: KCT0007571; registered on 2022/07/26 ( https://cris.nih.go.kr/cris/search/detailSearch.do/23192 ).

This study investigated prospective bidirectional relationships between depression and metabolic syndrome (MetS), and the moderating effects of race, sex, and health behaviors in a diverse cohort followed for 30 years.

Data were analyzed from the NHLBI CARDIA study, a 30 year-prospective study of young adults (N = 5113; M age = 24.76 (SD = 3.63) at baseline; 45% male) who were tested every 5 years between 1985-2015. Measures included biological assessments of MetS components, and self-reported depressive symptoms based on the Center for Epidemiologic Studies Depression (CESD) scale. Data analyses included bi-directional general estimating equations analyses of time-lagged associations between depressive symptoms and MetS.

There was a consistent, bi-directional relationship between depressive symptoms and MetS over time. Individuals with more CESD depressive symptoms were more likely to develop MetS over time compared to those reporting fewer symptoms (Wald Chi-Square = 7.09 (1), p < 0.008), and MetS was similarly predictive of CESD. MetS more consistently predicted depressive symptoms at each 5-year exam than depressive symptoms predicted MetS. Race and sex moderated relationships between depression and MetS, with White females, White individuals overall, and females overall demonstrating significant relationships. Health behaviors were not related to depression-MetS associations.

In a diverse young adult population prospectively followed into late middle age, MetS more consistently predicted depression over time than depression predicted MetS. The relation between MetS and depressive symptoms was moderated by race and sex, but not health behaviors.

The aim of this study was to evaluate the effects of 8 wk of time-restricted eating (TRE) along with a caloric restriction on metabolic profile, metabolic rate, symptoms of mood, and eating disorders and weight loss in women with overweight or obesity.

Women age 18 to 59 y with a body mass index of ≥25 kg/m² were enrolled in this parallel-arm, randomized, clinical trial. Participants were randomly allocated into two groups (8-h TRE or non-TRE group) using a 2:1 allocation strategy. Both groups received a diet plan with caloric restriction. Body weight, resting metabolic rate, metabolic profile, and symptoms of mood and eating disorders were evaluated at baseline and on follow up.

Thirty-six subjects were included in this study, with 24 in the TRE group and 12 in the non-TRE group. Subject in the TRE group showed more pronounced loss of weight, body fat mass, and fat-free mass than those in the non-TRE group. These losses were not associated with changes in resting metabolic rate, metabolic profile, and eating or mood disorder symptoms.

This study showed that 8 wk of TRE does not influence behavioral parameters in individuals with overweight or obesity, but could lead to weight loss.

Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.

Overweight/obese major depressive disorder (MDD) patients have a high probability of developing glucose metabolism disorders; however, the results are inconsistent due to the confounding variables involved in the studies. The purpose of this study was to explore the prevalence and risk factors for elevated fasting glucose in Chinese Han patients with overweight/obese first-episode and drug naïve (FEDN) MDD.

The study used a cross-sectional design and recruited 1718 FEDN MDD patients between the ages of 18 and 60 years. Socio-demographic information, anthropometric data, and biochemical parameters were collected. The 17-item Hamilton Assessment Scale for Depression (HAMD), the 14-item Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) positive subscale were used to assess symptoms of all patients.

MDD patients with elevated fasting glucose had higher TSH, TPOAb, TC, TG, LDL-C, systolic and diastolic blood pressure levels than those with normal fasting glucose. Logistic regression analysis showed that age, TSH, TgAb, TPOA, and TG were related factors for elevated fasting glucose, while TSH and combination all these five parameters had the potential to differentiate between patients with elevated fasting glucose and those with normal fasting glucose. Multifactorial regression analysis showed that TSH, TG, and LDL-C were independently associated with elevated fasting glucose.

Our findings suggest a high prevalence of elevated fasting glucose in overweight/obese FEDN MDD patients. Several clinically relevant factors and metabolic parameters are associated with elevated fasting glucose in overweight/obese FEDN MDD patients.

Due to the cross-sectional design, no causal relationship could be derived.

Observational studies indicated obesity and glutamatergic dysfunction as potential risk factors of depression, and reported disturbance of glutamine metabolism in obese state. However, it remains unclear whether the inter-relationships between obesity, glutamine and depression are causal.

We conducted two-sample bidirectional Mendelian Randomization (MR) analyses to explore the causalities between circulating glutamine levels, specific depressive symptoms, major depressive disorder (MDD) and body mass index (BMI). Univariable MR, multivariable MR (MVMR) and linkage disequilibrium score regression (LDSR) analyses were performed.

Genetic downregulation of glutamine was causally associated with MDD, anhedonia, tiredness, and depressed mood at the false discovery rate (FDR)-controlled significance level (estimate, -0·036∼ -0·013, P = 0·005 to P = 0·050). Elevated BMI was causally linked to lower glutamine level (estimate = -0·103, P = 0·037), as well as more severe depressed mood, tiredness, and anhedonia (estimate, 0·017∼0·050, P < 0·001 to P = 0·040). In MVMR analysis, BMI was causally related to depressed mood dependently of glutamine levels. Reversely, it showed limited evidence supporting causal effects of depression on glutamine levels or BMI, except a causal association of tiredness with elevated BMI (estimate = 0·309, P = 0·003). LDSR estimates were directionally consistent with MR results.

The present study reported that higher BMI was causally associated with lower glutamine levels. Both obesity and down-regulation of glutamine were causally linked to depression.