Depression includes different phenotypes. Modern-type depression (MTD) is a gateway disorder to pathological social withdrawal, known as hikikomori. Adverse childhood experiences (ACEs) are also important aetiologies of depression. Recently, immune imbalance has been proposed as a biological basis of depression. We hypothesised that peripheral immunological characteristics may be involved in subtyping of depression.

21 patients with major depressive disorder (MDD) and 24 healthy controls (HC) were recruited. Peripheral blood mononuclear cells (PBMCs) were examined for surface antigens by flow cytometry. Participants were administered psychological scales such as Patient Health Questionnaire (PHQ)-9, Modern-Type Depression Trait Scale (TACS-22), Hikikomori Questionnaire (HQ-25), Child Abuse and Trauma Scale (CATS).

MDD group showed significantly higher percentage of B cells than HC group (p = 0.032). MDD group presented a negative correlation between: PHQ-9 and CD8 T effector memory cells (r= -0.639, p = 0.002), TACS-22 and monocytes (r= -0.459, p = 0.036), HQ-25 and NK T cells (r= -0.638, p = 0.004), CATS and Intermediate monocytes (r= -0.594, p = 0.009).

MTD traits, hikikomori tendencies, and ACEs were correlated with specific characteristics of peripheral immune cells. Our results suggest that immune imbalance influences the diverse presentations of depression. Further validation is warranted by large-scale prospective studies.

Psychomotor retardation (PMR) is a predominant symptom in patients with major depressive disorder (MDD). The relationship between inflammation and PMR is the subject of ongoing debate. The glymphatic system (GS) is a waste clearance system in the brain that interacts with the immune system. Herein, we hypothesized that GS function moderates the association between inflammation and PMR.

A total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.

GS function in patients was impaired compared with that in HCs (t = -2.635, p = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (F = 6.725, p = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (F = 13.86, p = 0.047) and FC (F = 13.765, p < 0.001) in the motor circuit.

A well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.

Inflammation and metabolic dysfunction impair dopamine neurotransmission, which is thought to serve as a critical mechanism underpinning motivational deficits such as anhedonia across a range of psychiatric and neurological disorders. This difficult-to-treat transdiagnostic symptom has important implications for treatment resistant depression (TRD), and may warrant more targeted therapeutic approaches that address the underlying pathophysiological mechanisms. Using the adrenocorticotrophic hormone (ACTH) model of antidepressant treatment resistance we characterized the relationship between antidepressant-like and anhedonia-like behavioral responses to bupropion, mesocortical tyrosine hydroxylase (TH) expression, chronic low-grade inflammation, and metabolic changes in male rats. We demonstrate that chronic ACTH elicited both an antidepressant resistant- and anhedonia-like phenotype in forced swim and effort-related choice behavioral tasks, respectively. This was associated with decreased TH expression in the brain, increased central and peripheral markers of inflammation, and peripheral metabolic disturbances, including impairment of immune cell insulin action. Multivariate analysis revealed that peripheral interleukin-6 (IL-6) levels, immune cell glucose uptake and disturbance of nucleotide metabolism were strongly associated with anhedonia-like behavior. Post-hoc analyses further confirmed strong correlations between TH expression, inflammation and behavioral performance. These data suggest that stress hormone-induced upregulation of inflammation concurrent with the impairment of insulin-mediated glucose uptake into immune cells is associated with disruption of nucleotide metabolism, and potential impaired central dopamine synthesis contributing to the behavioral expression of anhedonia. These results suggest that immunometabolic perturbations concomitant with impaired insulin action at the level of the immune cell result in a metabolically deficient state that directly impacts nucleotide precursors essential for dopamine synthesis and effortful behavior. These results highlight the potential for immune and metabolic markers for individualized treatment of refractory depression and anhedonia.

Individuals raised in an urban environment (URBANs) show an exaggerated inflammatory response to the Trier Social Stress Test (TSST) compared with individuals raised in a rural environment (RURALs). The underlying mechanisms are unclear but may relate to childhood animal contact. As an exaggerated immune (re)activity plays a causal role in the pathogenesis of stress-associated disorders, these findings might explain the higher prevalence of stress-associated disorders in urban vs. rural areas.

We recruited physically and emotionally healthy male URBANs, raised in a city with more than 40,000 residents either in the absence (noPETs) or presence (PETs) of household pets. Participants were individually exposed to the TSST, and before and after the TSST, blood and saliva were collected for assessment of different stress-related parameters. An additional saliva sample before the TSST was collected for salivary microbiome analysis. Heart rate (HR) and HR variability (HRV) were recorded continuously. Mental and physical health status, early-life and perceived life stress, current animal contact, and subjective strain induced by TSST exposure were assessed using validated questionnaires.

Here we show that adult healthy male noPETs vs. PETs still reported less animal contact during adulthood and were characterized by deficits in their immunoregulatory and intestinal barrier function, which under basal conditions did not translate into a chronic low-grade inflammatory state. This was different under acute psychosocial stress conditions. Exposure to the TSST resulted in a facilitated mobilization of particularly neutrophil granulocytes in noPETs vs. PETs, accompanied by an enhanced pro- and compromised anti-inflammatory systemic stress response.

Together, the presence of pets seems to reduce the risk for URBANs to develop stress-associated disorders later in life (i.e., primary prevention) by facilitating immunoregulatory and barrier functions, in turn preventing an overshooting immune activation in response to acute stressors and chronic low-grade inflammation in response to repeated/chronic stressors.

This systematic review explores the associations between qualitative/quantitative changes in gut microbiota and psychopathological symptoms or other clinical features in patients with eating disorders (EDs). Secondary outcomes include exploring gut microbiota changes in EDs and potential relationships with psychotropic drug use.

A systematic search was conducted across biomedical databases from inception to June 2024 according to PRISMA guidelines. The risk of bias was assessed, and a narrative synthesis was performed due to the heterogeneity of the outcomes.

Only findings related to anorexia nervosa (AN) were identified. Ten studies, of which seven were longitudinal, two cross-sectional, and one interventional (N = 350 patients with AN, and 304 HCs), were included. Despite no clear links between diversity metrics and clinical symptoms being observed, specific taxa belonging to phylum Firmicutes, such as Clostridium, Roseburia, Lactobacillus, Faecalibacterium, and Bifidobacterium belonging to Actinobacteriota correlated with ED psychopathology, including anxiety and depressive symptoms.

Changes in microbiota were related to anxiety and depressive symptoms, as well as altered eating behaviours by modulating inflammation and insulin pathways through short-chain fatty acids (SCFAs), that also lead to neurotransmitter imbalances. Further studies are required to replicate these finding and to explore whether similar patterns are observed in other EDs.

Adverse childhood experiences (ACEs) are linked to later anxiety and depression, and inflammation has been implicated as a mediating mechanism. Black and Latinx men who have sex with men (MSM) face higher prevalences of ACEs, anxiety, and depression compared to White, heterosexual peers. Understanding the links between ACEs and mental health is crucial to addressing these disparities.

This study used structural equation modeling to test moderated mediation models examining inflammation as a mediator of the relationship between ACEs and symptoms of anxiety/depression and minority stress as a moderator on the path between ACEs and inflammation. Data was from a community sample of Black and Latinx MSM (n = 246; mean age = 22.6).

ACEs were significantly associated with symptoms of anxiety (B = 0.414; p < 0.001) and depression (B = 0.346; p < 0.001), but inflammation did not show a significant mediating effect. Additionally, the interaction between ACEs and minority stress had no significant indirect effect on anxiety/depression.

These findings underscore the possibility that inflammation may not represent the global perturbations of stress processes after ACEs at younger ages, particularly among a relatively healthy sample of emerging adults.

The study aims to explore the association between anti-inflammatory dietary variables and prevalence of depression and loneliness in older adults.

A cross-sectional secondary data analysis was performed using data from the English Longitudinal Study of Ageing (ELSA), targeting adults aged 50 and over.

Data from wave 9 of ELSA were utilised. Binary logistic regression was employed to estimate the Odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between participants' intake of fruits, vegetables, fish, nuts and seeds, legumes, and wholegrains, and the prevalence of depression and loneliness. Two sets of regressions were conducted: the first set examined each dietary component individually, while the second considered all variables simultaneously. Both models were tested with and without adjusting for covariates, including age, gender, ethnicity, self-rated weight, marital status, education, socio-economic status, and activity-limiting long-standing illnesses.

Of 4254 participants included in the analysis, 355 participants (8 %) had depression, and 623 (15 %) reported experiencing loneliness. An association was observed between higher intakes of fruits and lower prevalence of depression (OR = 0.89, 95 % CI: 0.79-1.00, p = 0.05), and between higher intakes of vegetables and lower prevalence of loneliness (OR = 0.91, 95 % CI: 0.83-1.00, p = 0.05). However, these associations lost statistical significance after adjustment for confounders. Similarly, the second model, which included all anti-inflammatory dietary variables, failed to show a significant association with depression and loneliness.

The study does not support the hypothesis that anti-inflammatory variables are associated with prevalence of depression and loneliness in older adults.

Periodontal disease (PD) is a common oral infection that is often exacerbated during pregnancy. Porphyromonas gingivalis (P. gingivalis), a keystone PD pathogen, promotes systemic inflammation, depressive-like behavior in animals, and can translocate to the brain and genital tract. Its capsular antigens (K1-K7) are key virulence factors. We hypothesized that seropositivity to specific P. gingivalis capsular K serotypes is associated with depressive symptoms and systemic inflammation during pregnancy.

In a prospective cohort of pregnant women (N = 114), depressive symptoms were assessed in each trimester of pregnancy using the Edinburgh Postnatal Depression Rating Scale (EPDS, ≥13 denoting moderate-to-severe depression symptoms). Plasma IgG antibodies against P. gingivalis K1-K7 serotypes and proinflammatory cytokines were measured. Statistical analyses included Firth's bias-reduced logistic regression and mixed-effects linear models.

Approximately 25 % of participants were seropositive for at least one K serotype. IgG seropositivity to P. gingivalis K1 serotype was significantly associated with moderate-to-severe depressive symptoms during the first trimester (EPDS≥13; P = 0.035). Additionally, aggregated K seropositivity was significantly associated with elevated plasma IL-10 levels during the first trimester (P < 0.05, adjusted for multiple comparisons). Other cytokines were unrelated to P. gingivalis K seropositivity.

We did not assess clinical or radiological manifestations of PD, antibodies to non-capsular P. gingivalis antigens, or the presence of other PD pathogens.

These results suggest the importance of integrating IgG K seropositivity (which, in addition to local oral pathogens may also reflect their distal translocation) with clinical, bacteriological and radiological measures when studying associations between periodontal disease and affective dysregulation in pregnancy.

In this study, we investigated the beneficial effect of Fucosterol on lipopolysaccharide (LPS) and chronic unpredictable mild stress (CUMS) induced depressive symptoms, elucidating the potential molecular mechanism by which Fucosterol regulates microglial phenotypes and neuroinflammation in the prefrontal cortex (PFC) of mice with depressive-like behaviours. Behavioural tests, including the tail suspension test (TST), forced swimming test (FST) and open field test (OFT), revealed that Fucosterol treatment attenuated depressive behaviours in LPS-treated and CUMS-induced mice. Further analysis of RNA sequencing (RNA-seq) data from CUMS-induced mice was performed to identify the potential pathways by which Fucosterol exerts antidepressant effects. Fucosterol suppressed microglial activation by inhibiting MAPK and ERK1/2 signaling, thereby reducing neuroinflammatory cytokine release in CUMS-induced mice. Furthermore, Fucosterol attenuated LPS-induced oxidation, proliferation and inflammation in primary microglial culture, and PD98059 (an ERK1/2 inhibitor) alleviated inflammation in primary microglial culture by inhibiting ERK1/2 activation. To further investigate whether Fucosterol exerts its anti-inflammatory effects through an ERK1/2-dependent pathway, we used an ERK1/2 agonist (Ro67-7476) in our study. The findings of this study demonstrated that Fucosterol alleviated depressive-like behaviours in CUMS-induced mice by inhibiting microglial hyperactivation through MAPK/ERK1/2 signaling suppression. These results suggested that Fucosterol may be effective in preventing depression, offering a potential strategy for developing antidepressant treatments based on natural compounds.

As population aging intensifies, depression emerges as a major global public health issue, especially affecting middle-aged and elderly individuals. While studies have investigated factors like sleep duration, physical activity, smoking, drinking habits, and comorbidity, the complex interplay and cumulative effect of these factors on the risk of depressive symptoms remain not fully understood.

This research utilizes data from the China Health and Retirement Longitudinal Study (CHARLS), encompassing observations from 2015 to 2020. The subjects included 8234 middle-aged and elderly individuals, accounting for a total of 22,570 observations. Lifestyle factors were represented by physical activity, smoking, and drinking habits, with the volume of moderate-to-vigorous physical activity (MVPA) quantified by quoting metabolic equivalents (MET). Multivariate logistic regression models were conducted for baseline analysis, and mixed-effects logistic regression models with random participant intercepts were constructed for the longitudinal analysis of the cohort. Moreover, interaction terms between these factors were included to assess their combined impact on the risk of depressive symptoms.

Longitudinal analysis revealed a notable correlation between short sleep duration (<7 h) and an elevated risk of depressive symptoms, evidenced by an adjusted odds ratio (OR) of 3.13 (95 % CI: 2.73-3.74). Conversely, long sleep duration (>9 h) was not associated with a marked change in risk of depressive symptoms (OR = 1.11, 95 % CI: 0.78-1.59, p = 0.59). High levels of physical activity (192-336 MET-h/week) were significantly linked to an elevated risk of depressive symptoms (OR = 1.70, 95 % CI: 1.19-2.42). Discontinuing smoking was significantly correlated with a lower risk of depressive symptoms (OR = 0.68, 95 % CI: 0.52-0.90). Subjects with two or more concurrent conditions exhibited a substantially higher risk of depressive symptoms (OR = 3.19, 95 % CI: 3.13-3.25). Investigating the combined influence of sleep duration, lifestyle elements, and concurrent conditions revealed that enhanced physical activity levels significantly decreased risk of depressive symptoms in participants with short sleep duration, adjusting the OR from 3.16 to 0.83 (95 % CI, 0.53-1.30). Among participants with short sleep duration, smoking and alcohol consumption patterns were linked to a decreased risk of depressive symptoms, although these associations lacked statistical significance. Relative to subjects without concurrent conditions, those harboring two or more such conditions faced a significantly heightened risk of depressive symptoms in the context of short sleep duration (OR = 3.00, 95 % CI: 2.24-4.03), a risk not observed in subjects with extended sleep duration. Moderate napping (0.5-1 h) among participants with short sleep duration was found to significantly mitigate risk of depressive symptoms (OR = 0.64, 95 % CI: 0.44-0.95), whereas in subjects with prolonged sleep duration, extended napping did not significantly alter risk of depressive symptoms.

The results, derived from a middle-aged and elderly Chinese population, may not be generalizable to other demographic groups or cultural contexts.

This study shows that short sleep duration, unhealthy lifestyle factors, and comorbidities significantly increase the risk of depressive symptoms in middle-aged and elderly individuals. Moderate physical activity, smoking cessation, moderate drinking, and appropriate napping can mitigate this risk, especially for those with short sleep duration. These findings highlight the need to address sleep quality, promote healthy habits, and manage comorbidities in mental health interventions for this population.

The effect of basal metabolic rate (BMR) on depression was unclear. This study investigated the potential role of BMR in the association of polycyclic aromatic hydrocarbons (PAHs) exposure and depression.

The study based on the National Health and Nutrition Examination Survey (NHANES). BMR was calculated using both the revised Harris-Benedict equation (BMR1) and the Mifflin-St Jeor equation (BMR2). Generalized linear and logistic regression models were applied to examine the associations between PAH metabolites, BMR, and depression. Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) were utilized to analyze the combined effects of multiple PAH metabolites. Mediation analysis was conducted to explore the role of BMR.

The study included 8323 participants. A 100 kcal/day increase in BMR1 and BMR2, the depression risk increased by 5 % (95%CI: 1.00, 1.10) and 7 % (95%CI: 1.02, 1.13), respectively. WQS model indicated that mixed PAH metabolites were negatively associated with BMR1 (β: -0.06, P = 0.020) and BMR2 (β: -0.06, P = 0.014). BKMR models showed that when all PAH metabolites were at P75 compared to P50, BMR1 and BMR2 decreased by 20.54 and 20.31 units, respectively, while the depression risk increased by 0.23 units (95 % CI: 0.07, 0.38). Mediation analyses suggested that BMR exerted a competitive mediation effect in the association between 1-NAP, 2-FLU, 1-PHE, 1-PYR, and depression.

PAH exposure led to a reduction in BMR and contributed to depression at high levels of exposure. An increase in BMR mitigated the impact of PAH exposure on depression.

The red blood cell distribution width-to-albumin ratio (RAR) serves as an indicator of systemic inflammation and nutritional status. This study examines the relationship between RAR and depressive disorder in U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES).

We applied logistic regression to evaluate the link between RAR and depressive risk, with its corresponding odds ratios (OR) and 95 % confidence intervals (CI) calculated. Restricted cubic spline (RCS) was adopted to assess the potential linear association, while the receiver operating characteristic (ROC) curve was used to evaluate the ability of RAR to predict the depressive risk, with the result presented as an area under the curve (AUC).

After adjusting for relevant covariates, a positive association between RAR and clinically relevant depression persisted (OR = 1.33, 95 % CI: 1.18-1.51, P < 0.001). Participants in the highest RAR quartile exhibited a greater risk of clinically relevant depression than those in the lowest quartile (OR = 1.36, 95 % CI: 1.10-1.67, P = 0.005). A linear relationship between RAR and clinically relevant depression was identified (P for non-linear = 0.473), with RAR showing a strong predictive ability for depressive risk (AUC = 0.7467). Stratified analysis showed significant interactions among smoking (P = 0.045), marital status (P < 0.001), and RAR's effect on depression outcome.

Elevated RAR is independently linked to clinically relevant depression, indicating its potential as a novel biomarker for mental health risk assessment. Further longitudinal studies are necessary to establish causality and evaluate its clinical relevance.

Previous investigations have established a notable correlation between depressive symptoms and stroke incidence, as well as the link between stroke occurrence and the ratio of family income-to-poverty ratio (PIR). The intricate dynamics between depressive states and the incidence of stroke mediated by PIR, however, remains inadequately understood.

The objective of this research is to scrutinize the link between depressive states and stroke, assessing how PIR functions as a mediator in this dynamic. Through an analysis of the economic status of individuals exhibiting depressive symptoms, this study explores their potential influence on the susceptibility to stroke. Such analysis aims to uncover the intricate interactions among depression, the PIR, and stroke occurrence.

Data from 2015 to 2018 NHANES assessed adults' depressive symptoms using PHQ-9 scores. Participants reporting a stroke diagnosis by medical professionals were identified as the stroke cohort. The income levels were assessed using the PIR. To examine the relationship between depressive symptoms and stroke, weighted multivariate linear regression models, curve-fitting analyses, and subgroup assessments were employed, alongside mediation analyses to determine the role of PIR as a mediator.

In the analysis of 7204 participants, the data revealed a robust positive association between depressive symptoms and stroke risk within the comprehensively adjusted model. Additionally, the mediation analysis demonstrated that the PIR contributed to 10.3188 % of the explained variability in the link between depressive symptoms and stroke incidence, serving as a specific mediator of this association.

The findings of this research indicate that there is a significant positive link between depressive symptoms and the incidence of stroke, with the PIR serving as a notable mediator.

Major depressive disorder (MDD) presents as a multifaceted syndrome with complex pathophysiology and variable treatment responses, posing significant challenges in clinical management. Neuroinflammation is known to play pivotal mechanism in depression, linking immune responses with central nervous system (CNS) dysfunction. This review explores the interplay between peripheral and central inflammatory processes in MDD, emphasizing discrepancies in biomarker validity and specificity. While peripheral markers like cytokines have historically been investigated as proxies for neuroinflammation, their reliability remains contentious due to inconsistent findings, lack of correlation with neuroinflammatory markers, the influence of confounding variables, and the role of regulatory mechanism within the CNS. Additionally, the human brain shows a pattern of regionalized inflammation. Current methodologies for investigating neuroinflammation in humans in vivo, including neural-derived extracellular vesicles (EVs) and positron emission tomography (PET) neuroimaging using translocator protein, offer promising avenues while facing substantial limitations. We propose that future research in MDD may benefit from combined microglia-derived EV-TSPO PET neuroimaging analyses to leverage the strengths and mitigate the limitations of both individual methods.

This study examines how quality of life is associated with sleep quality among Chinese university students through sequential mediation by perceived stress and sleep anxiety, using machine learning to uncover nonlinear effects.

A cross-sectional sample of 7128 university students (aged 18-28) from Eastern, Central, and Western China was recruited via stratified random and snowball sampling for regional diversity. Ordinary least squares regression and bias-corrected bootstrapping (5000 resamples) assessed direct and sequential mediation effects of perceived stress and sleep anxiety, estimating indirect effects with 95 % confidence intervals. Machine learning explored nonlinear relationships among variables.

Quality of life was strongly positively associated with subjective sleep quality. Mediation analyses confirmed that perceived stress and sleep anxiety independently and sequentially mediated this relationship. Machine learning revealed nonlinear patterns: the positive association between quality of life and sleep quality became more pronounced beyond a certain threshold, while higher levels of perceived stress and sleep anxiety were associated with sharper declines in sleep quality. Feature importance analysis ranked perceived stress as the top predictor, followed by sleep anxiety and quality of life.

Quality of life is significantly associated with sleep quality among Chinese university students, with perceived stress and sleep anxiety serving as potential sequential mediators. The identified nonlinear patterns suggest that higher levels of quality of life are linked to better sleep quality beyond a threshold, while elevated stress and anxiety correspond to sharper declines in sleep quality. These findings may inform future intervention strategies and support the need for longitudinal validation.

Plant-derived lipid nanoparticles (PDNPs) are nano-sized particles isolated from various edible plants that contain bioactive components involved in regulating biological responses. Here, we isolated maca-derived lipid nanoparticles (MDNPs) from Lepidium meyenii Walp (maca), evaluated their therapeutic effects using two representative lethal models of sepsis, and determined their multimodal anti-inflammatory mechanism that relied on broad sequestration and neutralization of multiple pro-inflammatory cytokines and acute phase proteins (APPs) through formation of a protein corona. Lipidomics of MDNPs revealed triacylglycerols and phytoceramides as major constituents. In vitro studies showed that MDNPs were non-toxic, reduced macrophage activation, and sequestered lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, while mitigating nuclear factor kappa B (NF-κB) activity. In a pre-established LPS-induced endotoxemia model, MDNP treatment significantly reduced systemic pro-inflammatory cytokines, reduced organ damage, and increased survival. Untargeted proteomics and bioinformatics analysis identified an enrichment in APPs present in MDNP protein coronas and corresponding inflammatory pathways modulated. The efficacy of MDNPs were further tested using a lethal polymicrobial sepsis model, where treatment significantly improved survival even in the absence of antibiotics. This study identifies MDNPs as an effective strategy capable of inducing potent anti-inflammatory responses, offering significant therapeutic potential for diseases such as sepsis, while informing the future design of synthetic lipid nanoparticles.

Depression is the most prevalent psychiatric illness, and its pathogenesis is associated with neuroinflammation. Follistatinlike protein 1 (FSTL1), a novel inflammatory protein, participates in the pathogenesis of diseases related to neuroinflammation. Therefore, we aimed to investigate the effect of FSTL1 in the pathogenesis of depression mediated using neuroinflammation-mediated models. Our results showed that lipopolysaccharide (LPS) administration could induce despair-like behavior and increase proinflammatory cytokine levels in both male and female mice. Then, a significant positive correlation between hippocampal Fstl1 mRNA expression, microglial activation and despair-like behaviors was observed in male mice. Moreover, knockdown FSTL1 significantly reduced microglial activation and the expression of proinflammatory cytokines, while overexpression of Fstl1 in hippocampus could exacerbate the activation of microglial under the LPS-induced condition in male mice. Mechanically, knockdown Fstl1 inhibited LPS-induced activation of BV2 microglia and reduced the production of proinflammatory cytokines, thereby protecting the survival of HT22 neurons. In conclusion, our results implied that Fstl1 may modulate despair-like behaviors through regulation of microglial activation and neuronal viability, which would lay the experimental and theoretical foundation for the neuroinflammatory mechanisms underlying depression.

Depression and anxiety impose a significant burden on older adults. While the protective effects of physical activity (PA) are well-documented, less is known about the interplay between PA, low-grade inflammation, and mental health. Biobehavioural mechanisms underpinning mental health may become more prominent when encountering novel stressors, which were particularly prevalent during the COVID-19 pandemic. Leveraging data of a national sample of older adults from England, this study tested (1) if pre-pandemic PA and its changes during the pandemic were associated with mental health responses; (2) if older adults with low-grade inflammation experienced greater increases in depression and anxiety, compared to pre-pandemic levels; (3) if PA attenuated the inflammation-mental health associations.

The study used data from the English Longitudinal Study of Ageing, a cohort study following a national sample aged 50 + (N = 5829). Information on mental health and PA was collected before the pandemic (2016/17 and 2018/19) and during November and December 2020. Inflammation was ascertained using pre-pandemic C-reactive protein (CRP). Analyses were adjusted for sociodemographic and health-related factors and pre-pandemic mental health.

Increasing PA from before to during the pandemic was linked to reduced odds of depression (OR = 0.955, 95 % CI [0.937; 0.974]) and anxiety (OR = 0.954, 95 % CI [0.927; 0.982]). Higher pre-pandemic PA was associated with reduced odds of depression (OR = 0.964, 95 % CI [0.948; 0.981]) and anxiety (OR = 0.976, 95 % CI [0.953; 1.000]), whereas elevated CRP was associated with 1.343 times higher odds of depression (95 % CI [1.100; 1.641]). PA did not attenuate the inflammation-depression association.

The findings suggest that PA may contribute to psychological resilience against stressful life events among older adults but does not appear to mitigate the adverse effects of systemic inflammation on mental health. Further research is needed to explore the psychobiological pathways underlying this protective mechanism.

Recent work leveraging artificial intelligence has offered promise to dissect disease heterogeneity by identifying complex intermediate brain phenotypes, called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the presence of nine DNEs derived from independent yet harmonized studies on Alzheimer's disease, autism spectrum disorder, late-life depression and schizophrenia in the UK Biobank study. Phenome-wide associations align with genome-wide associations, revealing 31 genomic loci (P < 5 × 10-8/9) associated with the nine DNEs. The nine DNEs, along with their polygenic risk scores, significantly enhanced the predictive accuracy for 14 systemic disease categories, particularly for conditions related to mental health and the central nervous system, as well as mortality outcomes. These findings underscore the potential of the nine DNEs to capture the expression of disease-related brain phenotypes in individuals of the general population and to relate such measures with genetics, lifestyle factors and chronic diseases.

This study investigated the prospective association of serum interleukin-1 beta (sIL-1β) and brain-derived neurotrophic factor (sBDNF) with 12-week antidepressant treatment outcomes in patients with depressive disorders. We analyzed baseline levels of sIL-1β and sBDNF in 1,086 patients participating in a naturalistic, stepwise antidepressant treatment study. Remission was defined by a Hamilton Depression Rating Scale score of ≤7 at 12 weeks. Logistic regression, adjusted for sociodemographic and clinical covariates, was used to assess the relationships between biomarker levels and treatment outcomes. Higher sIL-1β levels were significantly associated with non-remission at 12 weeks in patients with lower sBDNF levels, while in patients with higher sBDNF levels, sIL-1β did not significantly impact remission outcomes. The interaction between sIL-1β and sBDNF significantly associated with remission status, even after adjusting for confounders. The study suggests the significant role of the interplay between inflammatory and neuroplastic systems in influencing antidepressant treatment outcomes. These findings underscore the potential of integrating biomarker profiles to enhance personalized antidepressant strategies, advancing treatment precision in depressive disorders. Future research should focus on elucidating the dynamic mechanisms behind these biomarker interactions to further refine models that assess treatment responsiveness and develop targeted therapeutic interventions.

There is growing evidence that tobacco smoking causes depression, but it is unclear which constituents of tobacco smoke (e.g. nicotine, carbon monoxide) may be responsible. We used Mendelian randomisation (MR) to measure the independent effect of nicotine on depression, by adjusting the effect of circulating nicotine exposure [via nicotine metabolite ratio (NMR)] for the overall effect of smoking heaviness [via cigarettes per day (CPD)] to account for the non-nicotine constituents of tobacco smoke.

Univariable MR and multivariable MR (MVMR) were used to measure the total and independent effects of genetic liability to NMR and CPD on major depressive disorder (MDD). Our primary method was inverse variance weighted (IVW) regression, with other methods as sensitivity analyses.

For the exposures, we used genome-wide association study (GWAS) summary statistics among European ancestry individuals for CPD (n = 143 210) and NMR (n = 5185). For the outcome, a GWAS of MDD stratified by smoking status was conducted using individual-level data from UK Biobank (n = 35 871-194 881).

Genetic variants associated with NMR (n = 6) and CPD (n = 53).

Univariable MR-IVW indicated a causal effect of CPD on MDD [odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.04-1.23, P = 0.003] but no clear evidence for an effect of NMR on MDD (OR = 0.98, 95% CI = 0.97-1.00, P = 0.134). MVMR indicated a causal effect of CPD on MDD when accounting for NMR (IVW: OR = 1.19, 95% CI = 1.03-1.37, P = 0.017; Egger: OR = 1.13, 95% CI = 0.89-1.43, P = 0.300) and weak evidence of a small effect of NMR on MDD when accounting for CPD (IVW: OR = 0.98, 95% CI = 0.96-1.00, P = 0.057; Egger: OR = 0.98, 95% CI = 0.96-1.00, P = 0.038).

The role of nicotine exposure in risk of depression cannot be entirely dismissed. However, the causal effect of tobacco smoking increasing depression risk appears to be largely independent of circulating nicotine exposure, which implies the role of alternative causal pathways.

Chronic inflammation plays a prominent role in multiple medical disorders, including psychiatric diseases such as major depression. Exposure to inflammatory stimuli leads to changes in neurotransmitter systems and neurocircuits in the brain that are associated with depressive symptoms. Blockade of inflammatory cytokines can reduce depressive symptoms in medically ill and medically healthy individuals with depression. Increased levels of biomarkers of inflammation are associated with an overrepresentation of neurovegetative symptoms, including anhedonia, fatigue, and psychomotor slowing, and can predict response to antidepressant treatments. Importantly, however, increased inflammatory biomarkers occur in only a subgroup of individuals with depression. Thus, there appears to be a subset of patients with depression with a unique symptom presentation and treatment response whose disease is primarily driven by inflammation. Further identifying and characterizing this inflammatory subtype of depression can foster the development of treatments targeting the immune system and its effects on the brain. Moreover, by using this mechanism-based approach to parsing the heterogeneity of depression, we can refine our diagnostic nosology and model a strategy for precision medicine and targeted therapeutics in psychiatry.

Food-derived peptides offer a promising approach to alleviating depressive symptoms due to their safety and natural origin, avoiding the adverse side effects of conventional pharmacological treatments. This review aims to explore their potential in mitigating depressive symptoms. Antidepressant peptides from both animal and plant sources have been reviewed, while the animal models and evaluation methods used to assess their efficacy have been summarized. The review highlights four major mechanisms underlying their effects, namely modulation of gut microbiota and production of neuroactive metabolites, alteration of molecules associated with nervous system, normalization of hypothalamic-pituitary-adrenal axis dysregulation to reduce cortisol production, and suppression of pro-inflammatory cytokines linked to neuroinflammation. It also highlights the role of gut-brain axis in mediating the mechanisms, which has been insufficiently elucidated. However, the efficacy of antidepressant peptides for clinical use has not been established. The present review provides a reference for developing dietary interventions with food-derived peptides to supplement current therapeutic approaches.

Major depressive disorder (MDD) is associated with immune dysfunction. This study aimed to characterize the cellular immunophenotypes that may underpin immune dysregulation in MDD.

Peripheral blood mononuclear cell (PBMC) samples at baseline from participants with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study were included. A panel of 33 antibodies was analyzed using mass cytometry to compare the immune cell abundance and marker expression profiles between participants with mild and moderate/severe depression. Mass cytometry data were investigated using (1) Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP), (2) FlowSOM (self-organizing maps) for clustering, and (3) Significance Analysis of Microarrays (SAM) for statistical analyzes.

FlowSOM identified 8 clusters of distinct cell types. The abundance of cytotoxic T, NK, NK T, and Naïve B cells was significantly lower in participants with moderate/severe depression compared to mild depression. NKT cells had significantly lower CD56 and CD16 expression in patients with moderate/severe depression compared to patients with mild depression.

Our observations provide evidence for alterations in B, NKT, and NK cell abundance and their cell surface markers in moderate/severe depression. Further investigations into immune cell dysfunction in moderate/severe depression are necessary.

Major depressive disorder (MDD) is a leading cause of disability, and chronic inflammation is a contributing factor to its onset and progression. This study examined the relationship between genetic predisposition to inflammation and MDD risk in a nationally representative sample of U.S. military veterans, as well as psychosocial moderators of this association.

A composite polygenic risk score (PRS) for inflammatory biomarkers was derived from the UK Biobank and examined in relation to a positive MDD screen in 1,660 European-American veterans. The analysis adjusted for known correlates of inflammation and MDD, including medical conditions and cumulative trauma burden.

Each standard deviation increase in the inflammatory PRS was associated with more than two-fold increased odds of screening positive for MDD (OR = 2.51, 95% CI = 1.39-4.54). Interaction analyses revealed that optimism moderated this association; among those in the highest PRS tertile, individuals with high optimism were more than 30 times less likely to screen positive for MDD compared to those with low optimism (0.7% vs. 22.6%). Pathway-based analyses identified enrichment of immune- and brain-related gene sets, highlighting potential biological mechanisms linking inflammation and MDD.

Findings suggest genetic risk for inflammation contributes to MDD vulnerability and that optimism may buffer this risk.

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

Depression is a multifaceted condition with diverse underlying causes. Several contributing and inter-related factors such as genetic, nutritional, neurological, physiological, gut-brain-axis, metabolic and psychological stress factors play a role in the pathophysiology of depression. This review aims to highlight the role that nutritional factors play in the aetiology of depression. Secondly, we discuss the biomedical and functional pathology tests which measure these factors, and the current evidence supporting their use. Lastly, we make recommendations on how practitioners can incorporate the latest evidence-based research findings into clinical practice. This review highlights that diet and nutrition greatly affect the pathophysiology of depression. Nutrients influence gene expression, with folate and vitamin B12 playing vital roles in methylation reactions and homocysteine regulation. Nutrients are also involved in the tryptophan/kynurenine pathway and the expression of brain-derived neurotrophic factor (BDNF). Additionally, diet influences the hypothalamic-pituitary-adrenal (HPA) response and the composition and diversity of the gut microbiome, both of which have been implicated in depression. A comprehensive dietary assessment, combined with appropriate evaluation of biochemistry and blood pathology, may help uncover contributing factors to depressive symptoms. By employing such an approach, a more targeted and personalised treatment strategy can be devised, ultimately leading to improved patient outcomes.

To date, the mechanisms underlying the relationship between lung function and cognitive decline remain poorly understood. This study aims to investigate the mediating effect of depression in the longitudinal association between lung function and subsequent cognitive impairment (CI).

In the China Health and Retirement Longitudinal Study (CHARLS), a total of 7275 participants were included in the final analysis. Lung function was evaluated using peak expiratory flow (PEF) measured by a peak flow meter. A composite cognitive score was used to assess cognitive function. Linear and logistic regression models, along with bootstrap analyses, were used to investigate the mediating effect of depressive symptoms on the relationship between lung function and cognitive decline.

After adjusting for potential covariates, scores on both overall cognition and its four dimensions demonstrated an increasing trend from quartile 1 (Q1) to quartile 4 (Q4) of PEF and PEF% predicted (p < 0.001). Higher PEF values (Q4 vs Q1: OR = 0.93, 95 % CI 0.90 to 0.97, p = 0.001) as well as elevated PEF% predicted (Q4 vs Q1: OR = 0.94, 95 % CI 0.90 to 0.97, p = 0.001) were associated with a reduced risk of developing CI onset. The mediation effect of depression accounted for approximately 8.2 % of the total effect concerning lung function's impact on cognitive decline.

Higher PEF was associated with a slower rate of longitudinal cognitive decline in middle-aged and older adults. Although depressive symptoms acted as a mediator associated with the development of CI, the majority of variance remained unexplained.

Prolonged administration of antibiotics may be associated with depression due to the potential risk of dysbiosis. Thus, the restoration of microbial balance, through administration of prebiotics, might overcome the problem. This study investigated the mechanisms of antibiotic-induced depression, which were explored through statistical correlation analysis. The potential benefit of lactulose, a prebiotic, on this behavioral disorder was further assessed. The rats were assigned to groups receiving 102.8 mg/kg ciprofloxacin daily for 1, 8, 15, or 22 days. A different group of rat was given the same regimen for 8 days accompanied with lactulose at 2056 mg/kg. Upon completion of ciprofloxacin administration, the rats were tested for depression-like behavior (forced swimming test, FST; and sucrose preference test, SPT). They were then sacrificed for biochemical assessment in the hippocampus and prefrontal cortex. The mechanism studies revealed significant correlation between SPT vs. serotonin in the hippocampus, and SPT vs. serotonin, cortisol, NF-κB in the prefrontal cortex. Meanwhile, FST was significantly correlated with serotonin in the hippocampus and the prefrontal cortex, while in the prefrontal cortex it was significantly correlated with cortisol, NF-κB, and IL-6. Based on the afore-mentioned results, it was found that lactulose improved FST by targeting serotonin in the hippocampus. This study indicate that ciprofloxacin induce depression-like behavior via modulation of several neurotransmitter system as well as proinflammatory cytokines in the hippocampus and prefrontal cortex. The results further suggest the potential of lactulose to improve this behavior.

Depression and breast cancer (BC) demonstrate significant clinical comorbidity, yet their shared molecular mechanisms remain unclear, particularly regarding immune pathway regulation. This study systematically analyzed Depression-associated gene expression profiles (Gene Expression Omnibus (GEO) database) and BC transcriptomic data (The Cancer Genome Atlas (TCGA) database), identifying overlapping differentially expressed genes (DEGs). Functional enrichment (Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)) and protein-protein interaction (PPI) network analyses (STRING/Cytoscape) were employed to elucidate biological processes, followed by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic (ROC) curve validation to prioritize key genes. Immune infiltration patterns were assessed via the xCell algorithm, with Spearman correlation linking genes to immune subsets, and single-gene Gene Set Enrichment Analysis (GSEA) evaluating pathway activity. In total, 93 overlapping genes were identified, with predominant involvement in immune-related pathways being revealed by functional enrichment analysis. BHLHE41, EpCAM, and GSTM2 were prioritized as mechanism-associated genes through integrated LASSO regression and ROC analyses. Significant correlations were observed between these genes and specific immune cell populations. GSEA further linked these genes to immune response pathways, suggesting their regulatory roles. These findings highlight immune dysregulation as a shared mechanism underlying Depression-BC comorbidity, providing a foundation for developing early diagnostic strategies and therapeutic strategies targeting both conditions.

Background: Neuroinflammation lays a prominent impact in the pathophysiology of depression, and numerous studies have been conducted in recent decades. Bibliometric analysis is of important for understanding the hot spots and research trends in a certain subject field. However, no systematic bibliometric study exists in this field to date. The purpose of the study focused on the trends and hotspots in neuroinflammation of depression and provided future researchers with guidance and sights. Methods: Publications (2004-2023) were obtained from the WoSCC, and analyzed by HistCite, VOSviewer, CiteSpace, and Bibliometrix. The impact of publications was assessed by TGCS. Results: We analyzed 1,496 articles published in 409 journals and authored by 46,533 researchers across 72 countries and regions. The most prolific countries were China, the USA, and Brazil, and the most cited countries were the USA, followed with China and the UK, while the most prolific and cited institution was University Toronto (records=34, TGCS=2,137). Brain Behavior and Immunity is the leading journal that regularly published research in this field (records=93, TGCS=6,247). NLRP3 inflammasome, microglia, TNF-α, and brain-derived neurotrophic factor (BDNF) were the basis of neuroinflammation in depression. C-reactive protein, an important marker of inflammation, has been discussed for the longest time in this disease. In recent five years, two most frontier potential areas in studying depression were gut microbiota dysbiosis and BDNF. Conclusions: There remains a strong research basis for neuroinflammation in depression from this bibliometric analysis. Microglial activation, gut microbiota, cytokine signaling, and oxidative stress were research hotspots in recent years. In the future, chronic stress, hippocampal structure, and gut microbiota will continue to be studied in the field of neuroinflammation in depression. This study may benefit scientists in identifying potential directions for future study and providing clinicians with new ideas for treatment.

This study investigated whether HDL cholesterol mediates the relationship between inflammatory indicators and depression, using post-pandemic data in the context of metabolic disturbances and immune system impairment potentially caused by COVID-19.

This cross-sectional study, using data from the National Health and Nutrition Examination Survey (NHANES), included 5731 participants aged 20 years or older from August 2021 to August 2023. The Patient Health Questionnaire-9 (PHQ-9) assessed depressive symptoms. Multivariable logistic regression, Pearson correlation, and mediation analyses were conducted to evaluate odds ratios and associations between inflammatory indicators and depression.

Correlation analysis revealed significant negative associations between four inflammatory indicators (CRP, C-reactive protein; PC, platelet count; SII, systemic immune-inflammation index; PPN, product of platelet count and neutrophil count) and HDL cholesterol, as well as between HDL cholesterol and depression, while the inflammatory indicators were significantly positively correlated with depression (all p < 0.05). Furthermore, multivariable logistic regression models, adjusted for covariates, demonstrated that elevated levels of these four inflammatory indicators (CRP: adjusted OR = 1.011, CI = 1.003-1.025; PC: OR = 1.002, CI = 1.001-1.004; SII: OR = 1.002, CI = 1.001-1.003; PPN: OR = 1.002, CI = 1.001-1.004) were significantly associated with an increased risk of depression in the total study population. Finally, mediation analysis indicated that HDL cholesterol mediated the presumed causal associations between CRP (6.7-13.2 %), PC (4.5-12.8 %), PPN (4.8-14.9 %), and depression, whereas SII was identified as an independent predictor of depression development.

Targeting HDL cholesterol and inflammatory indicators such as CRP, PC, SII and PPN may provide potential interventions for mitigating depression risk.

Pediatric major depressive disorder (MDD) represents a leading cause of disability worldwide in children and adolescents, while its underlying pathophysiology remains largely elusive. The endocannabinoid system (ECS) and the hypothalamus-pituitary-adrenal (HPA) axis are considered intertwined regulatory systems crucially implicated in the pathophysiology of depressive disorders. This study explores the cross-sectional and longitudinal association between the ECS, specifically anandamide (AEA), and the HPA axis with its main effector cortisol and MDD status and severity in children and adolescents. Utilizing data from the omega-3-pMDD trial, a phase III Randomized Clinical Trial assessing the efficacy and safety of omega-3 fatty acid supplementation in pediatric MDD, we examined hair AEA and cortisol concentrations in 110 children and adolescents aged 8-17 years, with MDD. Associations between MDD, symptom severity and hair AEA and cortisol concentrations were explored across four measurement time points (baseline, week 6, 24 and 36). Additionally, 127 healthy children and adolescents were examined once to enable cross-sectional comparisons between MDD cases and healthy controls. Baseline comparisons for the 237 children and adolescents showed lower cortisol and AEA levels in hair of children and adolescents with MDD compared to healthy controls. Longitudinal multi-level analysis over all time-points further corroborated negative longitudinal associations between hair cortisol and depressive symptoms in children and adolescents with MDD. Taken together, reduced baseline AEA and cortisol levels emerge as robust biomarker in depressed youth, while the negative longitudinal association between hair cortisol and depression symptoms might provide useful for therapy monitoring purposes. These results hold implications for early detection, diagnosis, and therapeutic response prediction in pediatric MDD.

The human gut microbiome, comprised of trillions of microorganisms, plays a pivotal role in both physical and mental health. Recent research underscores the intriguing connection between gut bacteria and mental well-being, leading to the emergence of psychobiotics-microbes with mental health benefits. This review aims to explore fermented vegetables, a traditional dietary staple experiencing renewed interest, as a potential source of psychobiotics. Fermentation alters the microbial composition of vegetables, enriching them with beneficial bacteria such as Lactobacillus and Bifidobacterium. Various fermented vegetables, including kimchi, sauerkraut, and tempeh, host distinct bacterial communities. The review investigates how these psychobiotics may impact mental health through the gut-brain axis, a communication network between the gut and the central nervous system. Possible mechanisms encompass neurotransmitter modulation (e.g., serotonin, GABA), inflammation reduction and immunity modulation, and stress response enhancement through the hypothalamic-pituitary adrenal (HPA) axis. Clinical studies exploring the influence of fermented vegetables on mental health outcomes, including anxiety, depression, and cognitive function, are critically evaluated. The review assesses the efficacy of different fermented vegetables and probiotic strains while recognizing limitations in existing research and the necessity for further investigation.

Aims: To examine the association between depressive symptoms and metabolic profile in women with prior gestational diabetes mellitus (GDM) and early postpartum prediabetes, and to explore whether a mobile-based lifestyle intervention affected mental health outcomes. Methods: Secondary, exploratory analysis of a multi-centric randomized controlled trial (MELINDA), evaluating a mobile-based lifestyle intervention versus standard follow-up (control group) in women with prediabetes after GDM. The analysis included 166 participants who completed the Center for Epidemiologic Studies-Depression (CES-D) questionnaire [score of ≥16 being suggestive for (sub)clinical depression] at baseline (6-16 weeks postpartum) and one year post-randomization. Results: At one year, 26.5% of women (n = 44) reported depressive symptoms, with no significant difference between the intervention and control groups (30.5% vs. 22.6%, p = 0.293). Women with depressive symptoms (symptomatic women) were younger (30.9 ± 4.9 vs. 32.5 ± 3.8 years, p = 0.033) and were less often highly educated (61.4% vs. 80.3%, p = 0.028). At baseline, symptomatic women had a higher rate of metabolic syndrome (38.6% vs. 21.9%, p = 0.044), higher LDL-cholesterol [3.2 ± 0.8 vs. 2.8 ± 0.8 mmol/L, p = 0.009], lower quality of life (lower SF-36 scores, p < 0.050) and a higher level of anxiety based on the STAI-6 questionnaire (14.5 ± 3.6 vs. 11.2 ± 2.6, p < 0.001). These differences persisted at one year postpartum with worse metabolic profile, more anxiety and lower quality of life in symptomatic women. Conclusions: Depressive symptoms are common in women with prediabetes in early postpartum after GDM and are associated with a persistent worse metabolic profile, increased anxiety and lower quality of life postpartum. The mobile-based lifestyle intervention did not improve mental health.

We aimed to examine the effect of physical activity (PA) and weekend catch-up sleep (WCS) on depressive symptoms by evaluating their effects on high-sensitivity C-reactive protein (hsCRP) levels.

Data were collected from 10,715 adults aged ≥19 years. PA and depressive symptoms were assessed using self-report scales. The WCS was calculated by subtracting self-reported average weekday sleep hours from weekend sleep hours, and serum hsCRP levels were measured using immunoturbidimetric methods. Given that depressive symptoms are characterized by their multifaceted nature, we identified specific symptoms associated with hsCRP levels. Path analysis was used to investigate the association between PA, WCS, hsCRP, and depressive symptoms, and that between PA, WCS, hsCRP, and specific symptoms related to hsCRP.

Higher levels of PA and WCS were associated with a decreased risk of depressive symptoms through lowering hsCRP levels. Among various depressive symptoms, sleep problems and appetite changes were associated with hsCRP. In pathway analyses using them as dependent variables, higher levels of PA and WCS were also associated with a decreased risk of sleep problems and appetite changes through lowering hsCRP levels.

The current study employed a cross-sectional design, and WCS and PA were based on participants' self-reports rather than objective measurements.

Increased levels of PA and WCS may help alleviate depressive symptoms, particularly sleep problems and appetite changes, by mitigating chronic inflammation. Therefore, ensuring adequate exercise time and compensating for inadequate weekday sleep during weekends are crucial for maintaining mental well-being.