The impact of fluoxetine on serum lipid remains unclear due to inconsistencies in study findings. Differences in intervention duration, participant characteristics, and dosages may contribute to these variations. This meta-analysis and systematic review assessed fluoxetine's effects on lipid profiles in overweight or obese individuals.

A literature search was employed in Scopus, PubMed/Medline, Web of Science, and Embase for studies published up to December 2024. The DerSimonian and Laird random-effects model was used to estimate pooled weighted mean differences (WMD) and 95% confidence intervals (CI).

Nine studies met the inclusion criteria. Fluoxetine significantly reduced triglycerides (TG) (WMD: -22.04 mg/dL; CI: -42.61 to -1.46; P = 0.036) and increased HDL-C (WMD: 2.25 mg/dL; CI: 0.21 to 4.28; P = 0.030). No significant changes were noted in total cholesterol (TC) (WMD: 4.75 mg/dL; CI: -2.576 to 12.08; P = 0.204) or LDL-C (WMD: -0.35 mg/dL; CI: -11.15 to 10.44; P = 0.949). Greater TG reductions occurred with 60 mg/day fluoxetine (WMD: -43.86 mg/dL), baseline TG levels ≥ 150 mg/dL (WMD: -26.62 mg/dL), and interventions lasting ≤ 12 weeks (WMD: -26.88 mg/dL).

Fluoxetine significantly lowers TG and raises HDL-C in overweight or obese individuals. The effect on TG is more pronounced at 60 mg/day and in shorter interventions. Further research is needed to evaluate long-term impacts.

This research seeks to assess the connection between healthy sleep patterns and the occurrence of kidney stone disease (KSD) by analyzing data obtained from a large-scale cohort study.

We examined 313,870 initial participants without KSD from the UK Biobank. Five healthy sleep factors were assessed: no frequent excessive daytime sleepiness, early chronotype, no snoring, sleeping 7-8 h daily, and never or rarely experiencing insomnia at baseline. A healthy sleep score between 0 and 5 was assigned to participants according to these criteria. We utilized Cox proportional hazards models to calculate hazard ratios (HR) and 95 % confidence intervals (CI) between a healthy sleep score and the occurrence of KSD.

During the follow-up period, 3818 new cases of KSD were recorded. After comprehensive adjustments, every 1-point rise in the healthy sleep score was associated with an HR of 0.93 (95 % CI: 0.90-0.96). Additionally, individuals with a healthy sleep score of 5 had a 20 % lower risk of KSD compared to those with scores between 0 and 2.

Our study results indicate that adhering to a healthy sleep pattern can reduce the risk of KSD.

Depression not only fosters the development of metabolic syndrome through behavioral, physiological, genetic, and treatment-related factors, but it also doubles the risk of experiencing metabolic syndrome. The objectives were to assess the sociodemographic and clinical profile of patients with depressive disorder, to assess the various metabolic parameters of metabolic syndrome in patients with depressive disorder, and to study the association between the severity of depression and metabolic syndrome.

A cross-sectional study was conducted among patients diagnosed with depression (n = 160) attending the Psychiatry outpatient department of a tertiary healthcare facility in Puducherry. The Hamilton Depression Rating Scale (HAM-D) and modified National Cholesterol Education Program-Adult Treatment Panel-III (NCEP ATP-III) criteria were used to assess the severity of depression and diagnose metabolic syndrome, respectively.

The mean age at onset of depression was 31.4 years (+11.3); the duration of depression was 41.2 months (+32.5); and the severity of depression as assessed using the HAM-D was 17.9 (+6.3). The results showed that 27.5% of patients had metabolic syndrome. Factors associated with higher rates of metabolic syndrome included increasing age, female gender (79.5%), being single (25.0%), belonging to upper socioeconomic class (65.9%), non-Hindu religion (20.5%), and urban residence (72.7%) (P < .05). Patients with metabolic syndrome had later onset (36.4 years) and longer duration (51.6 months) of depression, more severe symptoms (18.2), and were more likely to have recurrent depressive disorder or dysthymia (88.6%) (P < .05). Furthermore, the current use of psychotropic medications (59.1%) and obesity (93.2%) were significantly associated with metabolic syndrome (P < .05).

This study reveals a high prevalence of metabolic syndrome among patients with depressive disorders linked to factors such as age, gender, marital status, socioeconomic status, religion, and urban residence. Integrated care approaches, including comprehensive screening and targeted interventions, are crucial for improving both mental and metabolic health outcomes.

Major depressive disorder (MDD) and metabolic syndrome (MetS) are both major health threats nowadays, and the relationship between them is complex and close. The purpose of this paper is to compare differences in the prevalence and risk factors of MetS in first hospitalized patients with MDD with and without antidepressant exposure.

A total of 636 first hospitalized MDD patients (study group) with antidepressant exposure and 345 drug-naïve patients (control group) were included in this study. Their socio-demographic data, routine biochemical indices, and psychological symptom assessment were collected.

There was no difference in the prevalence of MetS between the study group and the control group (F = 2.49, p = 0.115). Factors affecting MetS and its severity differed between the two groups, in the study group, the identified risk factors for MetS were onset age (B = 0.05, p <0.001, OR = 1.05, 95% CI = 1.02-1.08), TSH level (B = 0.42, p <0.001, OR = 1.53, 95% CI = 1.39-1.68). Meanwhile, in the control group, the identified risk factors for MetS were more extensive and they were, onset age (B = 0.11, p <0.001, OR = 1.12, 95% CI = 1.07-1.16), suicidal behavior (B = 1.54, p = 0.007, OR = 4.65, 95% CI = 1.51-14.33), HAMD scores (B = 0.23, p = 0.008, OR = 1.26, 95% CI = 1.06-1.49) and TSH levels (B = 0.33, p <0.001, OR = 1.39, 95% CI = 1.17-1.65). The number of risk factors identified was lower in the study group.

Antidepressant use was associated with greater MetS severity but did not affect overall prevalence. Antidepressants appear to modify MetS risk factors, highlighting the need to differentiate these effects from those in drug-naïve patients when developing MetS interventions for the MDD population.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link.

Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms.

790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants.

The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Depression and metabolic syndrome could exacerbate the risks of the other, leading to a series of severe coexisting conditions. One notable comorbidity that must be mentioned is obstructive sleep apnea (OSA). Current studies suggested that depression increases susceptibility to OSA. As the prevalence of depression rises, it becomes critical to prevent and manage its complications or comorbidities, including OSA. Predictive models, non-invasive electroencephalogram monitoring, genetic research, and other promising technologies are being applied to the prevention, diagnosis, and personalized treatment of depression and OSA.

Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability to psychopathology or confounded by unmeasured familial factors. The authors investigated the association between psychiatric conditions in young adulthood and the risk of cardiometabolic complications in middle adulthood, up to 40 years later.

This cohort study (N=672,823) identified all individuals and their siblings born in Sweden between 1955 and 1962 and followed the cohort through 2013. Logistic regression models were used to estimate the bivariate associations between 10 psychiatric conditions or criminal convictions and five cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the comorbidity among psychiatric conditions and criminal convictions. The cardiometabolic complications were then regressed on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs.

Each psychiatric condition significantly increased the risk of cardiometabolic complications. These associations appeared nonspecific, as multivariate models indicated that most were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals' general psychopathology and their siblings' cardiometabolic complications. The same pattern was evident for the specific internalizing and psychotic factors.

Associations between mental disorders in early life and later long-term risk of cardiometabolic complications appeared to be attributable to a general liability to psychopathology. Familial coaggregation analyses suggested that the elevated risk could not be attributed to confounders shared within families. One possibility is that lifestyle-based interventions may reduce the risk of later cardiometabolic complications for patients with several mental disorders.

Patients with affective and anxiety disorders are at risk of metabolic syndrome (MetS) and, consequently, cardiovascular disease and premature death. In this study, the course and treatment of MetS was investigated using longitudinal data from a naturalistic sample of affective- and anxiety-disordered outpatients (Monitoring Outcome of psychiatric PHARmacotherapy [MOPHAR]).

Demographics, clinical characteristics, medication use, and MetS components were obtained for n = 2098 patients at baseline and, in a FU-subsample of n = 507 patients, after a median follow-up (FU) of 11 months. Furthermore, pharmacological treatment rates of MetS were investigated at baseline and FU. Finally, demographic and clinical determinants of change in MetS (component) scores were investigated.

At baseline, 34.6 % of n = 2098 patients had MetS, 41.4 % of whom received treatment. Of patients with persisting MetS, 46.1 % received treatment for one (or more) MetS component(s) at baseline, and 56.6 % received treatment at FU. Treatment rates of solely elevated blood pressure and reduced HDL-cholesterol did significantly, but modestly, improve. Higher age, male sex, smoking behavior, low education, diabetes, and depressive versus anxiety disorder were predictors of worse outcome at FU on at least one MetS component.

We did not have data on lifestyle interventions as a form of treatment, which might partly have explained the observed low pharmacotherapeutic treatment rates.

MetS (components) show high persistence rates in affective- and anxiety-disordered patients, and are, despite adequate monitoring, undertreated over time. This indicates that adherence and implementation of monitoring protocols should be crucially improved in psychiatric outpatients in secondary care.

Metabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients.

We recruited 1718 unmedicated MDD patients in this cross-sectional study. MetS was defined based on the 2004 Chinese Diabetes Society Criteria. Serum thyroid hormones including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb) were examined. We used the logistic regression model to determine risk factors for MetS and examined the performance of the regression model by using the Area Under the Curve (AUC). In addition, we performed the trend test to test whether the results were robust.

The prevalence of MetS in unmedicated MDD patients was 34.4%. MDD patients with MetS had higher levels of serum TSH, TGAb, and TPOAb (all P < 0.001). Concurrently, serum TSH levels were independent risk factors for MetS in MDD patients (OR:1.49, 95%CI: 1.40-1.58), which could also distinguish MDD patients with and without MetS (AUC was 0.77). Additionally, in the trend test, the results also indicated a similar trend when TSH was used as a categorical variable (P for trend < 0.001).

This study suggests that TSH levels were independent risk factors for MetS in FEDN MDD patients (OR:1.49). The examination of thyroid function may contribute to the early detection of MetS.

The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment has shown promise in the treatment of psychiatric illness. We conducted a 4-month pilot study to investigate the effects of a KD on individuals with schizophrenia or bipolar disorder with existing metabolic abnormalities. Twenty-three participants were enrolled in a single-arm trial. Results showcased improvements in metabolic health, with no participants meeting metabolic syndrome criteria by study conclusion. Adherent individuals experienced significant reduction in weight (12 %), BMI (12 %), waist circumference (13 %), and visceral adipose tissue (36 %). Observed biomarker enhancements in this population include a 27 % decrease in HOMA-IR, and a 25 % drop in triglyceride levels. In psychiatric measurements, participants with schizophrenia showed a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1-point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %). This pilot trial underscores the potential advantages of adjunctive ketogenic dietary treatment in individuals grappling with serious mental illness.

Human gut microbiota are recognized as critical players in both metabolic disease and drug metabolism. However, medication-microbiota interactions in cardiometabolic diseases are not well understood. To gain a comprehensive understanding of how medication intake impacts the gut microbiota, we investigated the association of microbial structure with the use of single or multiple medications in a cohort of 134 middle-aged adults diagnosed with cardiometabolic disease, recruited from Alberta's Tomorrow Project. Predominant cardiometabolic prescription medication classes (12 total) were included in our analysis. Multivariate Association with Linear Model (MaAsLin2) was employed and results were corrected for age, BMI, sex, and diet to evaluate the relationship between microbial features and single- or multimedication use. Highly individualized microbiota profiles were observed across participants, and increasing medication use was negatively correlated with α-diversity. A total of 46 associations were identified between microbial composition and single medications, exemplified by the depletion of Akkermansia muciniphila by β-blockers and statins, and the enrichment of Escherichia/Shigella and depletion of Bacteroides xylanisolvens by metformin. Metagenomics prediction further indicated alterations in microbial functions associated with single medications such as the depletion of enzymes involved in energy metabolism encoded by Eggerthella lenta due to β-blocker use. Specific dual medication combinations also had profound impacts, including the depletion of Romboutsia and Butyriciocccus by statin plus metformin. Together, these results show reductions in bacterial diversity as well as species and microbial functional potential associated with both single- and multimedication use in cardiometabolic disease.

This study investigated prospective bidirectional relationships between depressive symptoms 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 National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Disease in Young Adults (CARDIA) study, a 30-year prospective study of young adults (N = 5,113; Mage = 24.76 [SD = 3.63] at baseline; 45% male) who were tested every 5 years between 1985 and 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 bidirectional general estimating equations analyses of time-lagged associations between depressive symptoms and MetS.

There was a consistent, bidirectional 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 χ²(1) = 7.09, p < .008, and MetS was similarly predictive of CESD. MetS more consistently predicted CESD scores at each 5-year exam than CESD predicted MetS. Race and sex moderated these relationships, with White females, White individuals overall, and females overall demonstrating significant relationships between CESD depressive symptoms and MetS. Health behaviors were not related to associations between CESD and MetS.

In a diverse young adult population prospectively followed into late middle age, MetS more consistently predicted depressive symptoms over time than depressive symptoms predicted MetS. The relation between MetS and depressive symptoms was moderated by race and sex, but not health behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Depression is associated with incident coronary heart disease (CHD) via a pathway that may be causal, but the mechanisms underlying this association are unclear. We assessed the extent to which metabolic syndrome (MetS) and its components (i.e., elevated waist circumference, low high-density lipoprotein [HDL] cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting plasma glucose) may mediate this association.

Data were Framingham Heart Study Research Materials obtained from the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) representing the total effect (aHRTE) of probable depression, measured via the Centers for Epidemiological Studies - Depression scale, on incident CHD over approximately 18 years. Using inverse odds ratio weighting, we decomposed this estimate into natural direct effects (aHRNDE) and natural indirect effects (aHRNIE) through potential mediators (measured approximately three years after depression).

Probable depression was associated with incident CHD (aHRTE=1.45, 95% confidence interval [CI]: 0.93, 2.25), and elevated waist circumference partially mediated this association (aHRNDE=1.34, 95% CI: 0.76-2.32; aHRNIE=1.08, 95% CI: 0.63-1.91). We did not find evidence of additional mediation by additional MetS components.

Elevated waist circumference appears to play a role in the association between depression and CHD.

Both abnormal glucose metabolism and anxiety have been reported to be common in major depressive disorder (MDD). However, few studies have explored glucose disturbances in first-episode and drug-naive (FEDN) MDD patients with anxiety. The purpose of this study was to examine the prevalence and risk factors of glucose disturbance in FEND MDD patients comorbid with anxiety.

1718 FEDN MDD patients were included in this study. The positive subscale of the Positive and Negative Syndrome Scale (PANSS), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) were used to measure psychotic, anxiety and depressive symptoms respectively. Sociodemographic and biochemical indicators were also collected.

The prevalence of glucose disorders in MDD patients combined with anxiety was 15.7 %, significantly higher than in MDD patients without anxiety symptoms (7.1 %). Glucose disturbances were associated with HAMD score, HAMA score, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), anti-thyroglobulin (TGAb), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), suicide attempts, and psychotic symptoms. Further logistic regression showed that illness duration, TSH, TGAb, and TPOAb levels were correlates of glucose disturbances in MDD patients with anxiety.

No causal relationship could be drawn due to the cross-sectional design.

Our findings suggest that TSH, TGAb and TPOAb may be promising biomarkers of glucose disturbances in MDD comorbid with anxiety, suggesting the importance of regular assessment of thyroid function parameters for abnormal glucose metabolism prevention.

Many studies have explored the relationship between depression and metabolic syndrome (MetS), especially in older people. China has entered an aging society. However, there are still few studies on the elderly in Chinese communities.

To investigate the incidence and risk factors of depression in MetS patients in mainland China and to construct a predictive model.

Data from four waves of the China Health and Retirement Longitudinal Study were selected, and middle-aged and elderly patients with MetS (n = 2533) were included based on the first wave. According to the center for epidemiological survey-depression scale (CESD), participants with MetS were divided into depression (n = 938) and non-depression groups (n = 1595), and factors related to depression were screened out. Subsequently, the 2-, 4-, and 7-year follow-up data were analyzed, and a prediction model for depression in MetS patients was constructed.

The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%. The prevalence of depression at the 2-, 4-, and 7-year follow-up was 29.55%, 34.53%, and 38.15%, respectively. The prediction model, constructed using baseline CESD and Physical Self-Maintenance Scale scores, average sleep duration, number of chronic diseases, age, and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up (area under the curve = 0.775, 95% confidence interval: 0.750-0.800, P < 0.001), with a sensitivity of 68% and a specificity of 74%.

The prevalence of depression in middle-aged and elderly patients with MetS has increased over time. The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.

Depression is associated with metabolic abnormalities linked to metabolic syndrome and tissue inflammation, but the interplay between metabolic markers and their association with subsequent depression is unknown. Therefore, we aimed to describe the network of metabolites and their prospective association with depressive symptoms.

The Finnish Depression and Metabolic Syndrome in Adults (FDMSA) cohort, originally a prospective case-control study, comprised a group with Beck Depression Inventory (BDI)-I scores ≥10 at baseline, and controls (n = 319, BDI-I < 10); mean (sd) follow-up time: 7.4 (0.7) years. Serum metabolic biomarkers were determined by proton nuclear magnetic resonance (NMR), and depressive symptoms sum-score by using the BDI-I. We examined the prospective associations between metabolites at baseline and BDI score at follow-up utilizing multivariate linear regression, parsimonious predictions models and network analysis.

Some metabolites tended to be either negatively (e.g. histidine) or positively associated (e.g. glycoprotein acetylation, creatinine and triglycerides in very large high density lipoproteins [XL-HDL-TG]) with depressive symptoms. None of the associations were significant after correction for multiple testing. The network analysis suggested high correlation among the metabolites, but that none of the metabolites directly influenced subsequent depressive symptoms.

Although the sample size may be considered satisfactory in a prospective context, we cannot exclude the possibility that our study was underpowered.

Our results suggest that the investigated metabolic biomarkers are not a driving force in the development of depressive symptoms. These findings should be confirmed in studies with larger samples and studies that account for the heterogeneity of depressive disorders.

Dietary fatty acids can affect brain health by modifying neuronal membrane fluidity. Dietary lipophilic index (LI) and load (LL) may be related to cell membrane fluidity. This study aimed to determine the relationship between dietary LI and LL with symptoms of depression, anxiety and stress.

In this cross-sectional study, taken from the YaHS (Yazd Health Study) population-based cohort, the data of 2,982 individuals was extracted. Several questionnaires- a 178-item Food Frequency Questionnaire (FFQ), Depression, Anxiety and Stress Scale 21 (DASS 21), and International Physical Activity Questionnaire (IPAQ)- were used to obtain information on dietary intake, mental status, and physical activity, respectively. LI and LL were calculated using dietary intake and the melting point of each fatty acid.

The analysis was performed on 2982 individuals. The odds ratio of depression in the second tertile of dietary LI compared to the first tertile was 0.815 (95% CI 0.66-1.00, P = 0.051, Ptrend = 0.017) and after adjusting confounders was 0.793 (95% CI 0.63-0.99, P = 0.043, Ptrend = 0.011). Also, LL was related inversely with anxiety (0.771, 95% CI 0.63-0.93, P = 0.003) that after multiple regression, OR of anxiety was 0.762 (95% CI 0.53-1.07, P = 0.045). The odds of stress in the third tertile of LL was 1.064 but not statistically significant (95% CI 0.88-1.28, P = 0.729).

This study showed an inverse association between dietary LI and depression symptoms. Anxiety and stress did not show a significant relationship with LI or LL.

Vulnerability theories propose that suboptimal levels of lipid markers and proinflammatory proteins predict future heightened depression. Scar models posit the reverse association. However, most studies that tested relationships between non-specific immune/endocrine markers and depression did not separate temporal inferences between people and within-person and how different immunometabolism markers related to unique depression symptoms. We thus used cross-lagged prospective network analyses (CLPN) to investigate this topic.

Community midlife women (n = 2224) completed the Center for Epidemiologic Studies-Depression scale and provided biomarker samples across five time-points spanning 9 years. CLPN identified significant relations (edges) among components (nodes) of depression (depressed mood, somatic symptoms, interpersonal issues), lipid markers [insulin, fasting glucose, triglycerides, low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL)], and proinflammatory proteins [C-reactive protein (CRP), fibrinogen], within and across time-points. All models adjusted for age, estradiol, follicle-stimulating hormone, and menopausal status.

In within-person temporal networks, higher CRP and HDL predicted all three depression components (d = 0.131-2.112). Increased LDL preceded higher depressed mood and interpersonal issues (v. somatic symptoms) (d = 0.251-0.327). Elevated triglycerides predicted more somatic symptoms (v. depressed mood and interpersonal problems) (d = 0.131). More interpersonal problems forecasted elevated fibrinogen and LDL levels (d = 0.129-0.331), and stronger somatic symptoms preceded higher fibrinogen levels (d = 0.188).

Results supported both vulnerability and scar models. Long-term dysregulated immunometabolism systems, social disengagement, and related patterns are possible mechanistic accounts. Cognitive-behavioral therapies that optimize nutrition and physical activity may effectively target depression.

Anxiety and metabolic impairments are often inter-related, but the underlying mechanisms are unknown. To seek RNAs involved in the anxiety disorder-metabolic disorder link, we subjected zebrafish larvae to caffeine-induced anxiety or high-fat diet (HFD)-induced obesity followed by RNA sequencing and analyses. Notably, differentially expressed (DE) transcripts in these larval models and an adult zebrafish caffeine-induced anxiety model, as well as the transcript profiles of inherently anxious versus less anxious zebrafish strains and high-fat diet-fed versus standard diet-fed adult zebrafish, revealed inversely regulated DE transcripts. In both larval anxiety and obesity models, these included long noncoding RNAs and transfer RNA fragments, with the overrepresented immune system and inflammation pathways, e.g., the "interleukin signaling pathway" and "inflammation mediated by chemokine and cytokine signaling pathway". In adulthood, overrepresented immune system processes included "T cell activation", "leukocyte cell-cell adhesion", and "antigen processing and presentation". Furthermore, unlike adult zebrafish, obesity in larvae was not accompanied by anxiety-like behavior. Together, these results may reflect an antagonistic pleiotropic phenomenon involving a re-adjusted modulation of the anxiety-metabolic links with an occurrence of the acquired immune system. Furthermore, the HFD potential to normalize anxiety-upregulated immune-related genes may reflect the high-fat diet protection of anxiety and neurodegeneration reported by others.

We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40-69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24-1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48-0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58-0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62-0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68-0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71-0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk.

We aimed to dissect the complex relations between depressive symptoms, antidepressant use, and constituent metabolic syndrome (MetS) components in a representative U.S. population sample. A total of 15,315 eligible participants were included from 2005 to March 2020. MetS components were defined as hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol, central obesity, and elevated blood glucose. Depressive symptoms were classified as mild, moderate, or severe. Logistic regression was used to evaluate the relationship between depression severity, antidepressant use, individual MetS components and their degree of clustering. Severe depression was associated with the number of MetS components in a graded fashion. ORs for severe depression ranged from 2.08 [95%CI, 1.29-3.37] to 3.35 [95%CI, 1.57-7.14] for one to five clustered components. Moderate depression was associated with hypertension, central obesity, raised triglyceride, and elevated blood glucose (OR = 1.37 [95%CI, 1.09-1.72], 1.82 [95%CI, 1.21-2.74], 1.63 [95%CI, 1.25-2.14], and 1.37 [95%CI, 1.05-1.79], respectively). Antidepressant use was associated with hypertension (OR = 1.40, 95%CI [1.14-1.72]), raised triglyceride (OR = 1.43, 95%CI [1.17-1.74]), and the presence of five MetS components (OR = 1.74, 95%CI [1.13-2.68]) after adjusting for depressive symptoms. The depression severity and antidepressant use were associated with individual MetS components and their graded clustering. Metabolic abnormalities in patients with depression need to be recognized and treated.

Dementia is a detrimental neuropathologic condition with considerable physical, mental, social, and financial impact on patients and society. Patients with metabolic syndrome (MetS), a group of diseases that occur in tandem and increase the risk of neurologic diseases, have a higher risk of dementia. The ratio between muscle and adipose tissue is crucial in MetS, as these contain many hormones, including myokines and adipokines, which are involved in crosstalk and local paracrine/autocrine interactions. Evidence suggests that abnormal adipokine and myokine synthesis and release may be implicated in various MetS, such as atherosclerosis, diabetic mellitus (DM), and dyslipidemia, but their precise role is unclear. Here we review the literature on adipokine and myokine involvement in MetS-induced dementia via glucose and insulin homeostasis regulation, neuroinflammation, vascular dysfunction, emotional changes, and cognitive function.

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.

Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and dyslipidaemia is well established, while evidence on antidepressants is mixed.

To investigate if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants and if CYP2C19 and CYP2D6 genetic variation plays a role.

Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein cholesterol (L/HDL-C) and triglycerides derived from blood samples. CYP2C19 and CYP2D6 metabolic phenotypes were assigned from genetic data. Linear regression investigated aims, adjusted for key covariates.

Of 469,739 participants, 36,043 took antidepressants (53% female, median age 58, 17% taking cholesterol-lowering medications) and 3255 took antipsychotics (58% female, median age 57, 27% taking cholesterol-lowering medications). Significant associations were found between use of each amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine and venlafaxine with higher total cholesterol, LDL-C, and triglycerides and lower HDL-C, compared to participants not taking each medication. Venlafaxine was associated with the worst lipid profile (total cholesterol, adjusted mean difference: 0.21 mmol/L, 95% confidence interval (CI): 0.17 to 0.26, p < 0.001). Antipsychotic use was significantly associated with lower HDL-C and higher triglycerides. In participants taking sertraline, CYP2C19 intermediate metabolisers had higher HDL-C (0.05 mmol/L, 95% CI: 0.01 to 0.09, p = 0.007) and lower triglycerides (-0.17 mmol/L, 95% CI: -0.29 to -0.05, p = 0.007), compared to normal metabolisers.

Antidepressants were significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring. Further research should investigate the mechanistic pathways underlying the protective effects of the CYP2C19 intermediate metaboliser phenotype on HDL-C and triglycerides in people taking sertraline.

Metabolic Syndrome (MetS) and depression comorbidity has been recognized, but its directionality is still uncertain. The aims of this study was to assess the association between depression (diagnosis and severity) and MetS (components, diagnosis and trajectory) in the baseline and over a 4-year follow-up period.

Baseline and follow-up data from 13,883 participants of the Brazilian Longitudinal Study of Adult Health were analyzed. The Clinical Interview Schedule Revised assessed depressive episode and its severity. MetS components and diagnosis were assessed according to the National Cholesterol Education Program Adult Treatment Panel III. Participants were grouped according to MetS trajectory as recovered, incident and persistent MetS. Logistic regression analysis was conducted estimating odds ratios (OR) and 95% confidence intervals (95%CI).

Baseline depression was positively associated with recovered (OR = 1.59, 95%CI 1.18-2.14), incident (OR = 1.45, 95%CI 1.09-1.91) and persistent (OR = 1.70, 95%CI 1.39-2.07) MetS. Baseline depression was also associated with large waist circumference (OR = 1.47, 95%CI 1.23-1.75), high triglycerides (OR = 1.23, 95%CI 1.02-1.49), low high-density lipoprotein cholesterol (OR = 1.30, 95%CI 1.08-1.56), and hyperglycemia (OR = 1.38, 95%CI 1.15-1.66) at follow-up. Having three or more MetS components at follow-up was associated with baseline depression, with a positive dose-response effect (OR = 1.77, 95%CI 1.29-2.43; OR = 1.79, 95%CI 1.26-2.54; OR = 2.27, 95%CI 1.50-3.46, respectively). The magnitude of associations was greater in severe depression, when compared to moderate and mild.

These results support that depression is a risk factor for the development of MetS and highlights the need to follow metabolic and cardiovascular alterations in the presence of depression.

The association of metabolic syndrome (MetS) with depression has been previously reported; however, the results are ambiguous due to imbalanced confounding factors. Propensity score-based analysis is of great significance to minimize the impact of confounders in observational studies. Thus, the current study aimed to clarify the influence of MetS on depression incidence in the U.S. adult population by using propensity score (PS)-based analysis.

Data from 11,956 adults aged 20-85 years from the National Health and Nutrition Examination Survey (NHANES) database between 2005 and 2018 were utilized. Using 1:1 PS matching (PSM), the present cross-sectional study included 4,194 participants with and without MetS. A multivariate logistic regression model and three PS-based methods were applied to assess the actual association between MetS and depression incidence. Stratified analyses and interactions were performed based on age, sex, race, and components of MetS.

After PSM, the risk of developing depression in patients with MetS increased by 40% in the PS-adjusted model (OR = 1.40, 95% confidence interval [CI]: 1.202-1.619, P < 0.001), and we could still observe a positive association in the fully adjusted model (OR = 1.37, 95% CI: 1.172-1.596, P < 0.001). Regarding the count of MetS components, having four and five conditions significantly elevated the risk of depression both in the PS-adjusted model (OR = 1.78, 95% CI: 1.341-2.016, P < 0.001 vs. OR = 2.11, 95% CI: 1.626-2.699, P < 0.001) and in the fully adjusted model (OR = 1.56, 95 CI%: 1.264-1.933, P < 0.001 vs. OR = 1.90, 95% CI: 1.458-2.486, P < 0.001). In addition, an elevation in MetS component count was associated with a significant linear elevation in the mean score of PHQ-9 (F =2.8356, P < 0.001). In the sensitivity analysis, similar conclusions were reached for both the original and weighted cohorts. Further interaction analysis revealed a clear gender-based difference in the association between MetS and depression incidence.

MetS exhibited the greatest influence on depression incidence in US adults, supporting the necessity of early detection and treatment of depressive symptoms in patients with MetS (or its components), particularly in female cases.

Psychiatric disorders are associated with cardiometabolic diseases, partly due to adverse drug effects with individual risk variabilities. Risperidone and sertraline are widely used for youths. Although they may be exposed to anthropometric changes, few data about this population exist. We evaluated the correlation between several blood parameters and body changes in a very small group of drug-naïve adolescents who had started risperidone or sertraline. We examined weight, waist circumference (WC), WC/height ratio and body mass index (BMI) at baseline (T0) and after at least three months of therapy (T1), and blood glucose and lipid profiles at T0. Here, we show significant increases in several anthropometric parameters in both groups, a negative correlation between HDL and ΔWC in the risperidone group and positive correlations between insulin and ΔBMI and between HOMA-IR and ΔBMI in the sertraline group. Despite the sample size, these results are important because it is difficult to study adolescents who are long-term-compliant with psychotropic drugs. This pilot study supports the importance of future large-scale investigations to understand the metabolic risk profiles of psychotropic drugs, their individual vulnerabilities and their underlying mechanisms. Simultaneous guideline-based psychiatric and metabolic interventions should be part of daily practice.

Pregnancy complications affect over one quarter of Australian pregnancies, and this group of mothers is vulnerable and more likely to experience adverse cardiometabolic health outcomes in the postpartum period. Metabolic syndrome is common in this population and may be associated with postpartum mental health issues. However, this relationship remains poorly understood. To compare the differences in psychosocial parameters and mental health outcomes between women with metabolic syndrome and women without metabolic syndrome 6 months after a complicated pregnancy.

This study is prospective registry analysis of women attending a postpartum healthy lifestyle clinic 6 months following a complicated pregnancy. Mental health measures included 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalised Anxiety Disorder questionnaire (GAD-7), self-reported diagnosed history of depression, anxiety and/or other psychiatric condition, and current psychotropic medication use.

Women with metabolic syndrome reported significantly more subjective mental health concerns, were more likely to have a history of depression and other psychiatric diagnoses and were more likely prescribed psychotropic medications. However, there were no significant differences in PHQ-9 and GAD-7 scores.

Amongst new mothers who experienced complications of pregnancy, those with metabolic syndrome represent a particularly vulnerable group with regards to psychosocial disadvantage and mental health outcomes. These vulnerabilities may not be apparent when using common standardised cross-sectional mental health screening tools such as PHQ-9 and GAD-7.

Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.

An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.

XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.

Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Child maltreatment is a common negative experience and has potential long-lasting adverse consequences for mental and physical health, including increased risk for major depressive disorder (MDD) and metabolic syndrome. In addition, child maltreatment may increase the risk for comorbid physical health conditions to psychiatric conditions, with inflammation as an important mediator linking child maltreatment to poor adult health. However, it remains unresolved whether experiencing child maltreatment increases the risk for the development of comorbid metabolic syndrome to MDD. Therefore, we investigated whether child maltreatment increased the risk for comorbid metabolic syndrome to depressed mood. Subsequently, we examined whether C-reactive protein (CRP), as an inflammatory marker, mediated this association. In addition, we investigated whether effects differed between men and women.

Associations were examined within cross-sectional data from the multiethnic HELIUS study (N = 21,617). Adult residents of Amsterdam, Netherlands, self-reported on child maltreatment (distinct and total number of types experienced before the age of 16 years) as well as current depressed mood (PHQ-9 score ≥ 10), and underwent physical examination to assess metabolic syndrome. The CRP levels were assessed in N = 5,998 participants. Logistic and linear regressions were applied for binary and continuous outcomes, respectively. All analyses were adjusted for relevant demographic, socioeconomic, and lifestyle characteristics, including ethnicity.

A higher number of maltreatment types as well as distinct types of emotional neglect, emotional abuse, and sexual abuse were significantly associated with a higher risk for current depressed mood. Child maltreatment was not significantly associated with the risk for metabolic syndrome in the whole cohort, nor within individuals with depressed mood. As child maltreatment was not significantly associated with the CRP levels, subsequent mediation analyses were not performed. No significant moderating effects by sex were observed.

In this multiethnic urban cohort, child maltreatment was associated with a higher risk for depressed mood. Contrary to our expectations, child maltreatment was not significantly associated with an increased risk for metabolic syndrome, neither in the whole cohort nor as a comorbid condition in individuals with depressed mood. As the data were cross-sectional and came from a non-clinical adult population, longitudinal perspectives in relation to various stages of the investigated conditions were needed with more comprehensive assessments of inflammatory markers.

Psychiatric disorders are complex, disabling, and chronic conditions that are often accompanied by one or more systemic medical comorbidities. In this narrative review, we provide an overview of the allostatic load concept, which represents a multi-system dysregulation in response to chronic stress and link it to systemic comorbidities associated with psychiatric disorders. We synthesized published literature gathered using Medline (Ovid), Scopus, and PsychInfo and identified a high frequency of systemic comorbidities for both mood and psychotic disorders. The identified cardiovascular, metabolic, and immune comorbidities may represent the result of chronic wear and tear caused by a complex interaction between chronic psychosocial stress, health risk behaviors, pharmacological stressors, and the biological systems involved in the development of allostatic load. These findings support the notion that psychiatric disorders should be re-conceptualized as systemic disorders, affecting the brain and systemic biological pathways in an interconnected fashion to result in systemic comorbidities. We suggest that the multi-systemic and multi-dimensional approach that drives the allostatic load concept should be considered for understanding comorbidities in vulnerable psychiatric patients.

Population-level telephone coaching services provide accessible behaviour change support for modifiable health risk behaviours. The NSW Get Healthy Information and Coaching Service® (GHS) is a free telephone-based coaching service in Australia, supporting improvements in healthy eating, physical activity and achieving or maintaining a healthy weight. This study compared measures of participation (such as program completion) and outcomes achieved immediate post-program (including changes in fruit and vegetable consumption, physical activity and weight) for GHS participants with and without a self-identified mental health condition (MHC). Secondary data analysis was conducted on service data collected at program intake and completion for individuals who enrolled in a coaching program between January 2018 and October 2019 (n = 5,629); 33% identified as having had an MHC. While those with and without an MHC had similar rates of completion, those with an MHC were less likely to complete a coaching program (31% vs 36%, p = .003). Participants with an MHC made significant positive changes to their fruit and vegetable consumption, physical activity (walking and moderate), weight and BMI, but not to waist circumference or vigorous physical activity. When comparing the magnitude of change for those with and without an MHC, individuals without made greater improvements to their weight (adjusted mean difference -0.623 kg, p = .034) and daily vegetable intake (adjusted mean difference -0.199 serves; p = .01). There were no differences for other variables. The GHS is an effective means of supporting behaviour change for people with an MHC who complete a coaching program. Further research should consider means of improving retention rates.

Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An important first step in this process is identifying risk factors for the incidence of major depression. There is accumulating biological evidence linking insulin resistance, another highly prevalent condition, and depressive disorders. The objectives of this study were to examine whether three surrogate measures of insulin resistance (high triglyceride-HDL [high-density lipoprotein] ratio; prediabetes, as indicated by fasting plasma glucose level; and high central adiposity, as measured by waist circumference) at the time of study enrollment were associated with an increased rate of incident major depressive disorder over a 9-year follow-up period and to assess whether the new onset of these surrogate measures during the first 2 years after study enrollment was predictive of incident major depressive disorder during the subsequent follow-up period.

The Netherlands Study of Depression and Anxiety (NESDA) is a multisite longitudinal study of the course and consequences of depressive and anxiety disorders in adults. The study population comprised 601 NESDA participants (18-65 years old) without a lifetime history of depression or anxiety disorders. The study's outcome was incident major depressive disorder, defined using DSM-IV criteria. Exposure measures included triglyceride-HDL ratio, fasting plasma glucose level, and waist circumference.

Fourteen percent of the sample developed major depressive disorder during follow-up. Cox proportional hazards models indicated that higher triglyceride-HDL ratio was positively associated with an increased risk for incident major depression (hazard ratio=1.89, 95% CI=1.15, 3.11), as were higher fasting plasma glucose levels (hazard ratio=1.37, 95% CI=1.05, 1.77) and higher waist circumference (hazard ratio=1.11 95% CI=1.01, 1.21). The development of prediabetes in the 2-year period after study enrollment was positively associated with incident major depressive disorder (hazard ratio=2.66, 95% CI=1.13, 6.27). The development of high triglyceride-HDL ratio and high central adiposity (cut-point ≥100 cm) in the same period was not associated with incident major depression.

Three surrogate measures of insulin resistance positively predicted incident major depressive disorder in a 9-year follow-up period among adults with no history of depression or anxiety disorder. In addition, the development of prediabetes between enrollment and the 2-year study visit was positively associated with incident major depressive disorder. These findings may have utility for evaluating the risk for the development of major depression among patients with insulin resistance or metabolic pathology.

A dramatic increase in the prevalence of major depression and diet-related disorders in adolescents has been observed over several decades, yet the mechanisms underlying this comorbidity have only recently begun to be elucidated. Exposure to western-style diet (WSD), high in both fats (45% kcal) and carbohydrates (35% kcal): e.g., high fat diet (HFD), has been linked to the development of metabolic syndrome-like symptoms and behavioral dysregulation in rodents, as similarly observed in the human condition. Because adolescence is a developmental period highlighted by vulnerability to both stress and poor diet, understanding the mechanism(s) underlying the combined negative effects of WSDs and stress on mood and reward regulation is critical. To this end, adolescent male C57 mice were exposed to vicarious social defeat stress (VSDS), a stress paradigm capable of separating physical (PS) versus psychological/emotional (ES) stress, followed by normal chow (NC), HFD, or a separate control diet high in carbohydrates (same sucrose content as HFD) and low in fat (LFD), while measuring body weight and food intake. Non-stressed control mice exposed to 5 weeks of NC or HFD showed no significant differences in body weight or social interaction. Mice exposed to VSDS (both ES and PS) gain weight rapidly 1 week after initiation of HFD, with the ES-exposed mice showing significantly higher weight gain as compared to the HFD-exposed control mice. These mice also exhibited a reduction in saccharin preference, indicative of anhedonic-like behavior. To further delineate whether high fat was the major contributing factor to these deficits, LFD was introduced. The mice in the VSDS + HFD gained weight more rapidly than the VSDS + LFD group, and though the LFD-exposed mice did not gain weight as rapidly as the HFD-exposed mice, both the VSDS + LFD- and VSDS + HFD-exposed mice exhibited attenuated response to the antidepressant fluoxetine. These data show that diets high in both fats and carbohydrates are responsible for rapid weight gain and reduced reward sensitivity; and that while consumption of diet high in carbohydrate and low in fat does not lead to rapid weight gain, both HFD and LFD exposure after stress leads to reduced responsiveness to antidepressant treatment.