Depression is a leading public health problem globally. Inflammatory mechanisms are thought to have a role in the pathophysiology of the disease.

Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were analyzed. The study design was cross-sectional. The main variables of the study were Depression and NPAR. Covariates of the study were age, sex, race, educational level, marital status, body mass index (BMI), and alcohol intake, as well as hypertension, coronary artery disease, cancer or malignancy, and diabetes.

Finally, 302 participants with Depression and 3731 without Depression were included in the analysis. Multiple logistic regression analysis using backward elimination showed that participants in the fourth quartile for NPAR are at greater risk for Depression compared with participants in the first quartile (OR: 1.55, 95 % CI: 1.08-2.22). Areas under the receiver operating curve (AUROC) of the NPAR to classify depression were 57.6 % (95 % CI: 53.3-61.9), 60.4 % (95 % CI: 53.2-67.6), 61.5 % (95 % CI: 55.2-67.7), and 70.0 % (95 % CI: 52.4-87.6) in the general population, males, participants hypertension and diabetes, respectively.

In conclusion, these results suggested that NPAR is associated with depression and could serve as a fair biomarker in subpopulations including males, and patients with diabetes and hypertension. It is suggested to use NPAR in combination with other associated factors with depression to classify or screen the subjects regarding depression in the general population. Also, present findings could be used to further elucidate the underlying pathophysiology of the disease.

Alzheimer's disease (AD) is a neurodegenerative condition that affects memory and cognition, with a higher prevalence in women. Given the lack of effective treatment, physical activity stands out as a complementary approach to prevent or delay disease progression. While numerous studies on humans and animals indicate that aerobic exercise induces brain changes, the impact of resistance exercise (RE) on AD is not fully understood.

This study aimed to investigate the behavioral and molecular changes induced by RE in female transgenic mice with AD at the early and advanced stages of the disease.

Adult (initial phase - 7 to 8 months of age, n = 32) and adult/elderly (advanced phase - 22 to 23 months of age, n = 32) female mice (2xTg-AD) for the APPSWE/PS1dE9 mutation were subjected to a four-week RE protocol. Mobility, anxiety-like behavior, long-term memory (LTM), and depressive-like behavior were assessed. Beta-amyloid (βA) and cytokines were quantified using the ELISA technique.

There was a progressive increase in strength in both trained groups at different ages. RE reversed memory deficits only in adult AD animals and the anxiety-like behavior only in adult/elderly AD animals. RE reversed depressive-like behavior in adult and adult/elderly AD animals. RE reduced βA only in adult AD animals. RE modified the expression of several cytokines in animals in the early and advanced stage of AD.

RE can be a promising strategy to minimize the deleterious effects of AD; however, its effectiveness may be more limited to the early stages of the disease.

More than half of adults with HIV in the United States are aged 50 or older. Older people with HIV (OPWH) are disproportionately affected by age-related health disparities and non-communicable diseases associated with inflammation. The current pilot randomized controlled trial (RCT) evaluated the feasibility and acceptability, while exploring signals of effects of a transdiagnostic cognitive behavioral therapy (CBT) modular group teaching skills to cope with distress, make positive health behavior changes, and ultimately reduce inflammation. Participants were 31 virally undetectable, and psychiatrically stable OPWH (age [Formula: see text]50 years). Participants were randomized 1:1 to enhanced usual care or CBT for HIV and Symptom Management (CHAMP). CHAMP consists of 12-weekly virtual group sessions led by two interventionists. Self-report questionnaires and intravenous blood draws were collected at baseline and follow-up. Intervention participants completed an exit interview. Of those screened eligible, 96.8% (30/31) were randomized (n = 15 per group), 86.7% (13/15) completed the intervention, and 87% (26/30) completed the follow-up. On acceptability questionnaires scaled 0-3, participants reported high satisfaction and the intervention to be of high quality (M(SD)=3.00(0.0) for both). They also indicated their needs were met (2.67(0.50)) and coping improved (2.60(0.52)). Intervention participants showed a mean decrease in anxiety (-1.07(6.08)) and depressive (-1.71(5.37)) symptoms on clinical screeners, and mean increase in quality of life (2.86(3.59)). CHAMP is both feasible and acceptable for OPWH. Exploratory analyses indicate favorable outcomes for improving psychological distress and health-related quality of life.

Evidence has shown that ibuprofen and celecoxib are effective in improving depressive symptoms, but their mechanisms of action are unclear. In this study, we aimed to determine the relationship between these two drugs and depressive disorder (DD) and elucidate potential mechanisms of action.

Relevant targets for ibuprofen, celecoxib, and DD were obtained and screened from multiple online drug and disease public databases. A protein-protein interaction network was obtained. The Centiscape and CytoHubba plug-ins were applied to screen for core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking was performed to predict the binding of ibuprofen and celecoxib to core targets. Examined the differences in core target protein expression between DD patients (DDs, n = 18) and healthy controls (HCs, n = 16) as a further experimental validation of the network pharmacology results.

In total, 220 potential targets for ibuprofen and 316 potential targets for celecoxib were identified and associated with DD. The antidepressant effects of both drugs involve many key targets in pathways such as "pathways in cancer" and "neuroactive ligand-receptor interaction," including ALB, BCL2, MAPK3, SRC, STAT3, EGFR, and PPARG. The binding affinity of ALB with ibuprofen is the strongest, and it is connected only by hydrophobic interactions. Celecoxib exhibits higher affinity at multiple targets such as SRC, EGFR, and PPARG, with stronger and more specific intermolecular interactions, including salt bridges and halogen bonds. Clinical trials have found that serum ALB expression in DDs is significantly lower than that in HCs (t = 6.653, p < 0.001), further confirming the potential role of ibuprofen in DD.

Ibuprofen and celecoxib primarily exert their antidepressant effects through targets and pathways related to inflammation, neural signaling, and cancer, with celecoxib showing a stronger potential antidepressant effect. The expression difference of the core target ALB between depression and healthy individuals further supports the potential effect of the drug on DD. Our findings propose new treatment strategies, support the link between inflammation and depression, and encourage reassessing existing medications for depression.

The effect of computed tomography (CT) vs invasive coronary angiography (ICA) on health status outcomes is unknown.

To evaluate CT and ICA first-test strategies on quality of life (QOL) and angina.

The Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial, conducted between October 2015 and April 2019 in 26 European centers, followed up patients with stable chest pain and intermediate probability of coronary artery disease for a median 3.5 years. Data analysis was from December 2023 to July 2024.

Random assignment to CT or ICA.

Patient-reported Euro QOL 5-dimensions descriptive system (EQ-5D-3L) visual analog scale (EQ-5D-3L-VAS) and 12-item Short Form Health Survey (SF-12) physical component score (SF-12-PCS) were primary prespecified QOL outcomes. Angina was the primary prespecified chest pain outcome. The EQ-5D-3L-VAS, summary index (EQ-5D-3L-SI), mental component summary (SF-12-MCS), and Hospital Anxiety and Depression Scale-anxiety subscale (HADS-A) and Hospital Anxiety and Depression Scale-anxiety subscale (HADS-D) were also evaluated.

Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 1735 (96.0%) in the CT group and 1671 (95.3%) in the ICA group completed at least 1 health status assessment during 3.5 years of follow-up. Health status outcomes were similar between groups, with significant improvements in all QOL outcomes (eg, mean EQ-5D-3L-VAS 3.5 year minus baseline score: CT = 4.0; 95% CI, 3.1-4.9; P < .001; ICA = 4.6; 95% CI, 3.6-5.6; P =.002), except HADS-D, which improved only in the CT group (mean EQ-5D-3L-VAS 3.5 year minus baseline score: CT = -0.2; 95% CI, -0.4 to 0; P = .04; ICA = -0.2; 95% CI, -0.4 to 0; P = .12). Female patients had worse baseline and follow-up QOL than male patients (eg, baseline EQ-5D-3L-VAS difference between men and women = 5.2; 95% CI, 4.0-6.3; P <.001 and at 3.5 years = 3.1; 95% CI, 1.9-4.4; P < .001) but showed greater improvements in EQ-5D-3L-VAS (-1.9; 95% CI, -3.4 to -0.5; P = .009), SF-12-PCS (-1.4; -2.1 to -0.7; P < .001), and HADS-A (0.3; 0-0.7; P = .04). Angina outcomes were comparable between groups at 3.5 years, with similar 1-year rates in the CT group but higher rates in female than male patients in the ICA group (10.2% vs 6.2%; P = .007).

Results of this secondary analysis of the DISCHARGE randomized clinical trial reveal that there was no significant difference in QOL or chest pain outcomes with CT vs ICA at 3.5 years. Female patients had worse health status than male patients at baseline and follow-up, and CT or ICA did not affect these differences.

ClinicalTrials.gov Identifier: NCT02400229.

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.

Anhedonia is a core diagnostic symptom of major depressive disorder (MDD). Post hoc analyses evaluated cariprazine plus antidepressant treatment (ADT) in patients with MDD and moderate-to-severe anhedonia.

Data were analyzed from a positive phase 3, randomized, fixed-dose (1.5 or 3 mg/d), double-blind, placebo-controlled, parallel-group cariprazine study (NCT03738215). Post hoc outcomes (e.g., change from baseline to week 6 in MADRS total score, MADRS anhedonia subscale score, MADRS anhedonia subscale item scores including item 8 [inability to feel]) were assessed in 2 anhedonia patient subgroups (baseline MADRS anhedonia subscale score ≥ 18; baseline MADRS anhedonia item 8 score ≥ 4) using a mixed-effects model for repeated measures.

Most patients met subgroup inclusion criteria (anhedonia subscale score ≥ 18 = 584 [77.8 %]; anhedonia item 8 score ≥ 4 = 508 [67.6 %]). LSMDs in change from baseline were statistically significant in favor of adjunctive cariprazine versus adjunctive placebo in the MADRS anhedonia subscale score ≥ 18 subgroup (MADRS total score: 1.5 mg/d = -3.4, p = .0006; 3 mg/d = -2.1, p = .0358; anhedonia subscale score: 1.5 mg/d = -2.1, p = .0010; 3 mg/d = -1.26, p = .0399) and in the anhedonia item 8 score ≥ 4 subgroup for adjunctive cariprazine 1.5 mg/d (MADRS total score: -3.2, p = .0037; anhedonia subscale score: -1.9, p = .0066). Significant differences were seen for adjunctive cariprazine versus adjunctive placebo on several anhedonia subscale single items, including anhedonia item 8 for the 1.5 mg/d dose.

Post hoc analysis.

In patients with MDD and moderate-to-severe anhedonia, adjunctive cariprazine improved symptoms of general depression and anhedonia, suggesting a potential benefit for patients with this clinically significant symptom.

N6-methyladenosine (m6A) is one of the most common post-transcriptional RNA modifications, which plays a critical role in various bioprocesses such as immunological processes, stress response, cell self-renewal, and proliferation. The abnormal expression of m6A-related proteins may occur in the central nervous system, affecting neurogenesis, synapse formation, brain development, learning and memory, etc. Accumulating evidence is emerging that dysregulation of m6A contributes to the initiation and progression of psychiatric disorders including depression. Until now, the specific pathogenesis of depression has not been comprehensively clarified, and further investigations are warranted. Stress, inflammation, neurogenesis, and synaptic plasticity have been implicated as possible pathophysiological mechanisms underlying depression, in which m6A is extensively involved. Considering the extensive connections between depression and neurofunction and the critical role of m6A in regulating neurological function, it has been increasingly proposed that m6A may have an important role in the pathogenesis of depression; however, the results and the specific molecular mechanisms of how m6A methylation is involved in major depressive disorder (MDD) were varied and not fully understood. In this review, we describe the underlying molecular mechanisms between m6A and depression from several aspects including inflammation, stress, neuroplasticity including neurogenesis, and brain structure, which contain the interactions of m6A with cytokines, the HPA axis, BDNF, and other biological molecules or mechanisms in detail. Finally, we summarized the perspectives for the improved understanding of the pathogenesis of depression and the development of more effective treatment approaches for this disorder.

To investigate the response to antidepressants while controlling for sex, which has been controversial, 92 outpatient males and females with major depressive disorder were assigned to sertraline (100 mg/day) or citalopram (40 mg/day) in two strata and were assessed using Hamilton depression rating scale (HDRS) scores and brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and cortisol serum levels in this 8-week, randomized, parallel-group, double-blind clinical trial. Data of 40 sertraline and 40 citalopram recipients with equal representation of males and females assigned to each medication were analyzed, while their baseline characteristics were not statistically different ( P  > 0.05). There were no significant differences between sertraline and citalopram recipients in outcome changes ( P  > 0.05), all of which indicated improvement, but a significant time-treatment-sex interaction effect in BDNF levels was observed ( P  = 0.035). Regarding this, subgroup analyses illustrated a significantly greater increase in male BDNF levels following sertraline treatment ( P  = 0.020) with a moderate to large effect size (Cohen's d = 0.76 and ). Significant associations were observed between percentage changes in IL-6 levels and BDNF levels in sertraline recipients ( P  = 0.033) and HDRS scores in citalopram recipients ( P  < 0.001). Sex was an effect modifier in BDNF alterations following sertraline and citalopram administration. Further large-scale, high-quality, long-term studies are recommended.

Background/Objectives: Depression is associated with an increased risk for the development and progression of cardiovascular disease. This research investigated the association between depressive symptoms and inflammation in the development of atherosclerotic coronary events. Methods: This retrospective observational study included 276 patients who were not previously diagnosed with atherosclerotic coronary artery disease at the beginning of the research. Participants were categorized using the Hamilton Depression Rating Scale (HDRS) and the Structured Clinical Interview for DSM-5 (SCID) into two groups: the depression group and the control group. Inflammatory biomarkers (C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cortisol) were measured at the beginning of the study, as well as at six months, one year, and two years. Results: Among patients with mild depression (17.3% vs. 4.2%) or moderate depression (15.4% vs. 6.7%), there were significantly more men than women, while among patients with very severe depression, there were significantly more women than men (21.7% vs. 11.5%). Participants with depression showed significantly higher increases at 2 years compared to baseline for all investigated parameters (p < 0.001). Depressed patients were significantly associated with an acute coronary syndrome (p = 0.038). Conclusions: This research highlights that individuals with depression face a greater risk of developing an acute coronary syndrome than those without depression.

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.

With the rapid progression of population aging, the number of frail individuals is steadily rising, making frailty a pressing public health issue that demands urgent attention. Compared to individuals with a single cardiovascular-metabolic disease, patients with cardiovascular-metabolic multimorbidity (CMM) are more prone to developing frailty. This study aimed to develop and validate a predictive model for assessing frailty risk in older adult patients with CMM.

The data came from participants in the 2015 wave of the China Health and Retirement Longitudinal Study (CHARLS). The study population comprised individuals aged 60 years and older with CMM and complete frailty scale measurements. Frailty status was evaluated using the Fried Frailty Scale. 26 indicators, including socio-demographic characteristics, lifestyle factors, overall health condition, and psychological well-being. The entire sample was randomly allocated into training and validation sets at a 7:3 ratio. LASSO regression and logistic regression was conducted to evaluate factors associated with frailty. A nomogram was constructed using the identified predictors to predict outcomes. The discrimination, accuracy, and clinical effectiveness of the model were evaluated by the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).

The study included 2,164 older adult CMM participants, with 387 (17.88%) displaying frailty symptoms. Binary logistic regression analyses revealed that depression, social activity, history of falls, life satisfaction, ADL scores, cognitive function, age and the number of CMDs were significantly associated with frailty. These eight factors were incorporated into the nomogram model, and the AUC values for the predictive model were 0.816 (95% CI = 0.787-0.848) and 0.816 (95% CI = 0.786-0.846) for the training and validation sets, respectively, indicating effective discrimination. Hosmer-Lemeshow test results showed p = 0.073 and p = 0.245 (both > 0.05), with calibration curves indicating strong alignment between the model's predictions and actual outcomes. The DCA demonstrated the model's substantial clinical utility.

The nomogram prediction model developed in this research is a reliable and effective tool for assisting clinicians in identifying frailty in older adult CMM patients at an early stage, providing a scientific foundation for individualized health management and intervention.

Physical activity (PA) is suggested to reduce the risk of depression, and inflammation is believed to play an important role in this antidepressant effect. The current study aims to investigate the effect of neutrophils, one of the most important markers of inflammation, on the relationship between PA and depression.

We cross-sectionally analyzed 34,317 adults who participated in the National Health and Nutrition Examination Survey. The moderation and mediation effects of neutrophils on the relationship between PA and depression were assessed using a four-way decomposition approach. Additional Mendelian Randomization (MR) analysis was conducted to validate the potential causal mediation effect.

PA was associated with lower odds of depression [Odds Ratio (OR): 0.67; 95 % Confidence Interval (CI): 0.56-0.79] and a lower level of neutrophils (OR: 0.83; 95 % CI: 0.77-0.90). Neutrophils were associated with higher odds of depression in a non-linear manner. While neutrophils did not modify the association between PA and depression, a significant mediating effect was observed. The influence of PA and neutrophils on depression was attributed to the controlled direct effect (96 % proportion) and the pure indirect effect (2 % proportion). MR analysis did not confirm a potential causal effect.

There is a close relationship between PA, neutrophils, and depression. The effect of PA on depression did not differ among participants with different levels of neutrophils. Although neutrophils mediated the association between PA and depression, this mediating effect was not causal. Other unknown factors closely related to neutrophils may be involved in this mediating process.

Although previous researches have suggested that certain dietary nutrients, such as carotenoids, have an effect on depression, epidemiological evidence on the relationship between lycopene and depression remains limited. This study aimed to investigate the association between dietary lycopene intake and depression risk in American adults.

Data from 18,664 participants in the National Health and Nutrition Examination Survey (NHANES, 2007-2016) were analyzed, with depression defined by a nine-item Patient Health Questionnaire (PHQ-9) score ≥ 10. Dietary lycopene intake was estimated from the mean of two 24-h dietary recalls. Binary logistic regression and restricted cubic spline (RCS) models were employed to assess the relationship.

Depression prevalence was 8.98%, and adjusted analyses indicated that higher dietary lycopene intake was significantly associated with a reduced depression risk compared to the lowest quartile (ORs for the second, third, and fourth quartiles: 0.851 [95% CI, 0.737-0.982], 0.829 [95% CI, 0.716-0.960], and 0.807 [95% CI, 0.695-0.938], respectively). Additionally, a U-shaped relationship was observed, with a reduction in depression risk associated with dietary lycopene intake ranging from 0 to 10,072 μg/d (P-non-linear = 0.017).

This study suggested that higher dietary lycopene intake may confer a protective effect against depression in American adults.

Neuropsychiatric disorders significantly impact global health and socioeconomic well-being, highlighting the urgent need for effective treatments. Chronic inflammation, often driven by the innate immune system, is a key feature of many neuropsychiatric conditions. NOD-like receptors (NLRs), which are intracellular sensors, detect danger signals and trigger inflammation. Among these, NLR protein (NLRP) inflammasomes play a crucial role by releasing pro-inflammatory cytokines and inducing a particular cell death process known as pyroptosis. Pyroptosis is defined as a proinflammatory form of programmed cell death executed by cysteine-aspartic proteases, also known as caspases. Currently, the role of pyroptotic flux has emerged as a critical factor in innate immunity and the pathogenesis of multiple diseases. Emerging evidence suggests that the induction of pyroptosis, primarily due to NLRP inflammasome activation, is involved in the pathophysiology of various neuropsychiatric disorders, including depression, stress-related issues, schizophrenia, autism spectrum disorders, and neurodegenerative diseases. Within this framework, the current review explores the complex relationship between pyroptosis and neuropsychiatric diseases, aiming to identify potential therapeutic targets for these challenging conditions.

Stress is an adaptive response to different events in daily life that could strain physically, emotionally, or psychologically. Adolescence is an important developmental period due to physical, psychological, and social maturation. The aim of our study is to state whether chronic unpredictable mild stress (CUMS) during adolescence in male rats can cause anxiety and depression in adulthood and whether vitamin C (Vit C) can prevent this problem or not.

For this purpose, we performed behavioral tests, including open field test, elevated plus maze, and forced swimming test. In addition, we investigated the metabolism of serotonin, the level of inflammation, oxidative stress and brain-derived neurotrophic factor (BDNF) in the brain cortex tissue of animals.

Results indicated that CUMS exacerbates mood-related behaviors by affecting the brain oxidative stress balance, inflammatory response, and serotonin metabolism. Moreover, we found that CUMS-Vit C co-treatment could significantly reverse CUMS-induced complications by restoration of the mentioned biochemical parameters.

Taken together, we would like to suggest the use of Vit C supplementation as a safe, inexpensive, and effective strategy for the management of CUMS.

Reporting the histological effects of chronic stress on certain oral tissues, as well as the capacity of Thymus vulgaris (thyme) to protect tissues from stress and link both serum cortisol and serotonin levels.

30 rats were randomly divided into a trio of groups: normal control (no treatment), stress group (chronic stress without treatment), and treatment group (chronic stress treated with thyme at a dose of 200 mg/kg BW orally via needle gavage daily for 21 days). At the end of the experiment, tongues and major sublingual glands (SLGs) were surgically removed and processed for histological and histochemical studies. Blood samples were taken shortly before scarification for the biochemical study of cortisol and serotonin serum levels.

Examination of tongue and SLG sections of the stress group indicated significant alterations in histology and changes in SLG secretion. An examination of tongue and SLG histological sections of the thyme-treated group are showed an improvement. Chronic stress raises cortisol serum levels and lowers serotonin serum levels.

Chronic stress causes alteration of the tongue and major SLG histology, as well as changes in SLG secretion. Thyme may protect tissues from stress, and there is a relation between cortisol and serotonin levels.

Although increasing evidence suggests that depression/distress involves inflammatory processes, its potential sex differences and the temporal directions for this association remain elusive.

We examined the temporal association between serum inflammatory mediators and depression/distress as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) and the Kessler Psychological Distress Scale (K6), in nondepressed working men and women (n = 61 and 43, respectively) by a 16-month prospective design.

Fully adjusted partial correlation analyses revealed that, in men, a lower IFN-γ predicted subsequent increases in CES-D and K6 scores, whereas a higher TNF-α predicted increased K6 scores. In women, a higher IFN-γ predicted a subsequent increase in the CES-D score. CES-D and K6 scores did not predict inflammatory mediators at follow-up.

The finding suggests that inflammatory activation precedes depression/distress with distinct sex differences.

Black cumin (Nigella sativa L.) (family Ranunculaceae) is a largely utilized therapeutic herb worldwide. This comprehensive review discusses the pharmacological benefits of black cumin seed oil, focusing on its bioactive component thymoquinone (TQ). The review is structured as follows: First, we examine the antimicrobial properties of black cumin oil, followed by an analysis of its antioxidant capabilities. Finally, we explore its therapeutic potential, particularly in neurodegenerative diseases and COVID-19. Phytochemicals from N. sativa have exhibited potential for developing novel preventive and therapeutic strategies against jaundice, gastrointestinal disorders, skin diseases, anorexia, conjunctivitis, dyspepsia, intrinsic hemorrhage, amenorrhea, paralysis, anorexia, rheumatism, diabetes, hypertension, fever, influenza, eczema, asthma, cough, bronchitis, and headache. The broader spectrum of application for N. sativa and its essential bioactives have certainly enhanced the commercial value of this seed oil. TQ, a major constituent of black cumin seed oil, has numerous beneficial properties. Researchers have extensively studied black cumin seed oil and its major component, TQ. These studies have revealed a wide range of pharmacological properties, including anticancer, immunomodulatory, analgesic, antimicrobial, antidiabetic, and anti-inflammatory effects. Additionally, TQ has shown neuroprotective, spasmolytic, bronchodilatory, hepatoprotective, renoprotective, gastroprotective, and antioxidant activities.

The therapeutic targeting of the intestinal microbiota has gained increasing attention as a promising avenue for addressing mood disorders. This study aimed to assess the potential effect of supplementing standard pharmacological treatment with the probiotic kefir in patients with Major Depressive Disorder (MDD).

Thirty-eight female participants diagnosed with moderate MDD by the Hamilton Rating Scale for Depression (HAM-D) were selected to receive the probiotic kefir in conjunction with antidepressant therapy for 12 weeks. The participants were evaluated at baseline (T0) and 90 days after probiotic kefir supplementation (T90). HAM-D scores and blood samples were collected at both time points.

Probiotic supplementation significantly reduced MDD severity, as evidenced by lower HAM-D scores compared to baseline. Probiotic consumption for 90 days also significantly decreased interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels compared to baseline. However, probiotic kefir supplementation did not significantly affect serum serotonin levels. Additionally, after 90 days of probiotic consumption, insulin and morning cortisol levels were significantly reduced. In contrast, no significant changes were observed in serum levels of prolactin, vitamin D, and afternoon cortisol.

This study provides valuable insights into the potential benefits of probiotics, specifically kefir, as adjunctive therapy for female patients with MDD. The findings highlight promising results in ameliorating depressive symptoms and modulating inflammatory and hormonal markers.

Maternal depression during and after pregnancy is a worldwide public concern. Low omega-3 FAs levels and intake in women during pregnancy were associated with a high rate of maternal depression and poor pregnancy outcomes. The study examines the association between FAs intake and levels and prenatal depressive and anxiety symptoms among pregnant Arabic-speaking women in Oman.

In 302 pregnant Omani women, level of depression and anxiety is assessed at the 8-12 and 24-28 weeks of pregnancy using the Arabic version of (EPDS). Seafood and the omega-3 FAs intakes of pregnant women has been quantified by using a validated (FFQ). FAs analysis of erythrocytes was carried out using the method of Folch et al. RESULTS: Maternal depression and anxiety symptoms (30.5 % and 26.1 %) were associated with low fish consumption and omega-3 FAs intake with depressive and anxiety symptoms (p = 0.01), Women with antenatal depression or anxiety symptoms had a lower erythrocyte concentration of arachidonic acid (20:4 n-6), (p = 0.01), total omega 6 FAs, (p = 0.03), docosahexaenoic acid (22:6 n-3) (p = 0.03), docosapentaenoic acid (22:5 n-3) (p = 0.04), eicosapentaenoic acid (20:5 n-3) (p = 0.005), total omega 3 FAs (p = 0.005), omega-3 index (p = 0.01), compared to healthy pregnant women. These findings did not change after adjusting for potential confounders.

Maternal omega-3 FAs exert a favourable effect on vital perinatal health outcomes. Fish and seafood intake or omega-3 FAs supplementation are highly recommended for women during pregnancy to ensure the well-being of both the mother and fetus.

The objective of this study was to explore the serum levels of IL-1, IL-6, IL-10, TNF-a, and high-sensitivity C-reactive protein (hs-CRP) in patients with depression before and after treatment and their correlation with the clinical symptoms of depression.

Fifty depression patients newly diagnosed and untreated in the Fourth People's Hospital of Wuhu were chosen as the depression group, while 50 healthy individuals from the same period served as the control group. We contrasted the serum levels of these markers of inflammation in both groups. After 8 weeks of SSRI antidepressant therapy, changes in inflammatory cytokines, hs-CRP, and HAMD-17 scores were evaluated in the depression group.

The levels of serum inflammatory cytokines and hs-CRP in patients with depression were higher than the healthy control group significantly (P < 0.05). After treatment, the levels of serum inflammatory cytokines and hs-CRP in patients with depression decreased significantly (P < 0.05). The total score of HAMD-17 and the scores of sleep, cognitive impairment, inhibition, and anxiety somatization factors in the depression group were decreased than those before treatment (P < 0.01). The serum IL-1 concentration in the depression group inversely related to the decrease in the HAMD-17 inhibition factor (R = -0.359,P = 0.011); The serum IL-6 concentration change rate positively correlated with the reduction rate of the cognitive impairment factor of HAMD-17 (R = 0.426,P = 0.017); the change rate of hs-CRP concentration was positively correlated with the reduction rate of the anxiety somatization factor of HAMD-17 (R = 0.343,P = 0.015).

Antidepressant treatment affects the levels of serum inflammatory cytokines and hs-CRP significantly, and is correlated with changes in clinical symptoms.

This study aimed to investigate the association between depressive symptoms and the incidence of thyroid nodules (TNs) in Chinese adults, and explore whether the development, persistence, or recovery from depressive symptoms influences the risk of developing TNs.

A total of 1,537 Chinese adults who underwent medical check-ups, including blood tests, Zung Self-Rating Depression Scales (SDS), and thyroid ultrasound examinations, were included. The association between depressive symptoms and TN prevalence was evaluated, and 818 participants free of TNs at baseline were followed over time. TN incidence rates were analyzed across different mental health statuses: depression-free, depression-developed, depression-recovered, and depression-persistent.

The prevalence of depressive symptoms was 31.95%, significantly higher in women than in men (42.60% vs. 25.82%). The prevalence of TNs was also higher in women (38.68% vs. 21.52%). Among women, participants with depressive symptoms had shorter height, higher levels of fasting plasma glucose (FPG), triglycerides (TG), and glutamyl transpeptidase (GGT), lower high-density lipoprotein cholesterol (HDL-C), and a significantly higher prevalence of TNs (46.44% vs. 32.92%, p < 0.01) compared to those without depressive symptoms. Although the FPG levels in depressive women were significantly higher than in non-depressive women, the levels of FPG in both groups remained within the clinically normal range. These differences were not observed in men. Over a mean follow-up of 2.75 years in women, the depression-persistent group (16.48/100 person-years) had a significantly higher TN incidence compared to the depression-free (6.43/100 person-years; age-adjusted HR: 2.679, 95% CI: 1.513-4.742, p = 0.001).

Women with persistent depressive symptoms had a higher risk of developing TNs, suggesting that mental health status may influence TN development in women.

Rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) are autoimmune illnesses characterised by chronic inflammation demonstrating differential associations with psychiatric conditions.

In this matched-cohort study, we aimed to investigate whether the associations between these inflammatory illnesses and mental disorders are predominantly the consequence of the burden of the former or whether common causes might underpin the susceptibility to both.

Using Czech national inpatient care data, we identified individuals with RA or axSpA during the years 1999-2012. We investigated the occurrence of psychiatric outcomes up to 2017 using stratified Cox proportional hazards models. In evidence triangulation, we assessed the potential moderation by age at inflammatory illness, the associations relative to counterparts with other similarly burdensome chronic illnesses and the temporal ordering of conditions.

Both RA and axSpA were associated with mood and anxiety disorders and behavioural syndromes. In evidence triangulation, the associations with depression showed a decreasing age-at-inflammatory-illness gradient in RA; the association between RA and depression was stronger than that between other chronic illnesses and depression; and excluding prevalent depression attenuated the RA-depression association. RA showed consistent inverse associations with schizophrenia and Alzheimer's disease.

Common aetiologies might be involved in increasing the risk of developing both RA and depression. The consistent inverse associations between RA and schizophrenia and between RA and Alzheimer's disease suggest that at least part of these associations might also be a consequence of shared aetiologies as well as potential medication effects.

People with autoimmune arthritides are more likely to experience mood and anxiety disorders, even relative to counterparts with other similarly burdensome chronic illnesses.

The prevalence of mental illness in Taiwan increased. Identifying and mitigating risk factors for mental illness is essential. Inflammation may be a risk factor for mental illness; however, the predictive power of inflammation test values is unclear. Artificial intelligence can predict the risk of disease. This study was the first to conduct risk prediction based on the combination of individual inflammation test values.

A retrospective longitudinal design was adopted to analyze data obtained from a medical center. Patients were enrolled if they had received blood tests for inflammation. Propensity score matching was employed for within-group comparisons. A total of 231,306 patients were enrolled. A deep neural network model was employed to establish a predictive model.

Among inflammation markers, high-sensitivity C-reactive protein concentrations were associated with the greatest risk of mental illness (37.45%), followed by the combination of individual inflammation test values (32.21%). The more abnormal a participant's inflammation values were, the higher the risk of mental illness (aHR = 1.301, p <.001). Specifically, high-sensitivity C-reactive protein concentration was the most indicative marker for predicting mental illness. Inflammation markers exhibited certain correlations with the type of mental illness. When the same variables were considered, statistical analysis and the deep neural network had similar results. After feature extraction was incorporated, the performance of the deep neural network model improved (excellent, area under the curve = 0.9162) and could effectively predict the risk of mental illness.

Inflammation values could predict the risk of developing mental illnesses in general and the risk of developing certain types of mental illness.

In patients with major depressive disorder (MDD) and animal models of depression, key pathological hallmarks include activation of microglia as well as atrophy and loss of astrocytes. Under certain pathological conditions, microglia can inflict damage to neurons and astrocytes. However, the precise mechanisms underlying how activated microglia induced astrocyte atrophy and loss remain enigmatic. In this study, a depression model induced by chronic social defeat stress (CSDS) is utilized. The results show that CSDS induces significant anxiety- and depression-like behaviors, along with notable astrocyte atrophy and apoptosis, microglial activation, and elevated levels of microglial interleukin-6 (IL-6). Subsequent studies demonstrate that IL-6 released from activated microglia promotes astrocyte apoptosis. Furthermore, the knockdown of the P2X7 receptor (P2X7R) in microglia, which is implicated in the stress response, reduces stress-induced microglial activation, IL-6 release, and astrocyte apoptosis. Direct inhibition of microglia by minocycline corroborates these effects. The selective knockdown of IL-6 in microglia and IL-6 receptors in astrocytes effectively mitigates depression-like behaviors and reduces astrocyte atrophy. This study identifies microglial IL-6 as a key factor that contributes to astrocyte apoptosis and depressive symptoms. Consequently, the IL-6/IL-6R pathway has emerged as a promising target for the treatment of depression.

The aim of this narrative review is to familiarize clinicians, especially digestive surgeons, to adequately use of serum C-reactive protein as a reliable noninvasive biomarker in diverse practical clinical situations. We hope that the review will help clinicians for their decision-making when facing various digestive diseases including operative and nonoperative pathologies such as anastomotic leakage, pancreatitis, emergency situation, and digestive cancer management and prognosis.

Depression is associated with diabetes, but the underlying causes remain unclear. To better understand depression in diabetes, this study investigated associations between 135 inflammatory and neurological protein biomarkers and depressive symptoms in individuals with diabetes.This cross-sectional study included 430 adults with a known diabetes duration <1 year from the German Diabetes Study (GDS), in whom biomarkers were measured in serum and depressive symptoms were evaluated at baseline and annually over 5 years using the Center for Epidemiological Studies Depression Scale (CES-D). Based on the information on depressive symptoms from the baseline and follow-up visits (n=305, ≥3 time points), we subdivided the sample into individuals with persistent or recurrent and transient or never depressive symptoms. We assessed the associations of each biomarker with baseline CES-D score (continuous) and persistent/recurrent depressive symptoms using multiple linear and logistic regression models, respectively.After adjustment for covariates, we identified a three-protein signature associated with baseline CES-D score and persistent/recurrent depressive symptoms. CUB domain-containing protein 1 (CDCP1) and NAD-dependent protein deacetylase sirtuin-2 (SIRT2) were positively associated with baseline (β 1.24 (95% CI 0.19 to 2.29); β 0.89 (95% CI 0.06 to 1.72)), respectively) and persistent/recurrent depressive symptoms (OR 1.58 (95% CI 1.08 to 2.31); OR 1.32 (95% CI 1.03 to 1.71), respectively), whereas leptin receptor (LEPR) was inversely associated with baseline (β -0.99 (95% CI -1.87 to -0.11)) and persistent/recurrent depressive symptoms (OR 0.70 (95% CI 0.49 to 0.99)). However, results were not significant after adjustment for multiple testing.In conclusion, the three-protein signature identified may provide insights into mechanisms underlying depressive symptoms in diabetes and might open new therapeutic avenues.The trial registration number of the study is NCT01055093.

Interleukin-6 (IL-6) is a crucial cytokine involved in inflammation and immune regulation. However, the detection of IL-6 with ultrasensitivity and high specificity remains a significant challenge due to the inherent complexity of biofluids. Herein, we present a digital surface enhanced Raman scattering (SERS) immunoassay using core-shell Au@Ag-Au nanotags for IL-6 detection with ultrasensitivity and high reliability. A low-cost silicon chip was functionalized as capture substrates, employing novel SERS nanotags that exhibit strong, robust and reproducible signals at single-nanoparticle resolution as the amplification element. We proposed two analytical methods to validate single-molecule events follow a Poisson distribution and to quantify protein biomarkers over a broad linear dynamic range, respectively. The strong alignment between theoretical and experimental results enhances the method's reliability. Our assay provides two readouts: colorimetric analysis by naked eyes for high concentrations (>1 ng/mL) and digital SERS analysis for low concentrations. Following method optimization, we obtained a linear range from 100 fg/mL to 1 ng/mL (R2 = 0.994) with a limit of detection (LOD) of 12.4 fg/mL, suitable for clinical applications. The method was tested for IL-6 quantification in healthy human serum and saliva, with recoveries from 92.4% to 105.3%. Finally, the immunoassay demonstrated strong consistency with the standard clinical laboratory method when tested with clinical serum samples. Thus, our proposed the digital SERS immunoassay is a promising tool for the precision clinical diagnosis of IL-6-related diseases or other conditions.

Insulin resistance and inflammation are components of a biological framework that is hypothesised to be shared by type 2 diabetes and depression. However, depressive symptoms include a large heterogeneity of somatic and cognitive-affective symptoms, and this may obscure the associations within this biological framework. Cross-sectional and longitudinal data were used to disentangle the contributions of insulin resistance and inflammation to somatic and cognitive-affective symptoms of depression.

This secondary analysis used data from the Emotional Distress Sub-Study of the GRADE trial. Insulin resistance and inflammation were assessed using the HOMA-IR estimation and high-sensitivity C-reactive protein (hsCRP) levels, respectively, at baseline and at the study visits at year 1 and year 3 (HOMA-IR) and every 6 months (hsCRP) for up to 3 years of follow-up. Depressive symptoms were assessed at baseline using the Patient Health Questionnaire (PHQ-8), and a total score as well as symptom cluster scores for cognitive-affective and somatic symptoms were calculated. For the cross-sectional analyses, linear regression analyses were performed, with inflammation and insulin resistance at baseline as dependent variables. For the longitudinal analyses, linear mixed-effect regression analyses were performed, with inflammation and insulin resistance at the various time points as dependent variables. In all analyses, depressive symptoms (total score and symptom cluster scores) were the independent variables, controlled for important demographic, anthropometric and metabolic confounders. For the analysis of insulin resistance (HOMA-IR), data from 1321 participants were analysed. For the analysis of inflammation (hsCRP), data from 1739 participants were analysed.

In cross-sectional analysis and after adjustment for potential confounders, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in HOMA-IR (p=0.007), but not with hsCRP (0.6% increase, p=0.283). The somatic symptom score was associated with a 5.8% increase in HOMA-IR (p=0.004). Single-item analyses of depressive symptoms showed that fatigue (3.6% increase, p=0.002) and increased/decreased appetite (3.5% increase, p=0.009) were significantly associated with HOMA-IR cross-sectionally. The cognitive-affective symptom score was not significantly associated with HOMA-IR at baseline. In longitudinal analyses, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in hsCRP over time (p=0.014), but not with HOMA-IR over time (0.1% decrease, p=0.564). Again, only the somatic symptom cluster was significantly associated with hsCRP over time (5.2% increase, p=0.017), while the cognitive-affective symptom score was not.

The results highlight the associations of depressive symptoms with markers of inflammation and insulin resistance, both cross-sectionally and longitudinally, in individuals with type 2 diabetes. In particular, somatic symptoms of depression appear to be the driver of these associations, even after controlling for concomitant conditions, with a potential role for fatigue and issues with appetite.

ClinicalTrials.gov NCT01794143.

Late-life depression (LLD) has been linked to increased likelihood of dementia, although mechanisms responsible for this association remain largely unknown. One feature frequently observed in both LLD and dementia is elevated levels of plasma inflammatory markers. The present study aimed to compare the levels of 12 plasma inflammatory markers between older people with LLD and controls, and to explore whether these markers, along with clinical characteristics, can predict dementia in patients with LLD within 3 years of follow-up. Using multiple linear regression with stepwise adjustment, we compared levels of plasma inflammatory markers (IL-1β, IL-1ra, IL-6, IL-10, IL-17a, IL-18, IL-33, TNFα, CD40L, IFN-γ, CCL-2 and CCL-4) between 136 inpatients with LLD (PRODE cohort) and 103 cognitively healthy non-depressed controls (COGNORM cohort). In the PRODE cohort, follow-up data was available for 139 patients (of them 123 had data on baseline plasma inflammatory markers); 36 (25.9%) developed dementia by Year 3 (n = 31 for those with cytokine data). Using Cox proportional hazards regression, we explored whether inflammatory markers and clinical characteristics of LLD (age of onset, treatment response, number of episodes) predicted progression to dementia during follow-up. Levels of IL-1ra, CCL-2, CCL-4, IFN-γ and IL-17a were significantly higher in LLD patients compared to controls in the majority of models. However, none of the inflammatory markers predicted progression from LLD to dementia in the PRODE cohort. Among clinical features, only poor response to treatment significantly predicted higher risk of progression to dementia.

Mental ill-health is a common and growing issue, affecting 1 in 8 individuals or 970 million people worldwide in 2019. Histidine-containing dipeptides (HCDs) have been suggested to mitigate some aspects of mental ill-health, but a quantitative synthesis of the evidence is lacking. Therefore, a systematic review and meta-analysis of randomized controlled trials was conducted.

To summarize the evidence on the effects of HCDs on mental health outcomes.

A systematic literature search was performed using electronic databases (Medline via Ovid, Embase via Ovid, Scopus, Google Scholar, and Cochrane) from inception to October, 2022.

Two authors independently extracted data using a structured extraction format.

Data analysis was performed using STATA version 17. Random-effects models were used, and heterogeneity was assessed using the I2 test. Quality appraisal was performed using the Cochrane risk-of-bias 2.0 tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

5507 studies were identified, with 20 studies fulfilling the inclusion criteria. Eighteen studies comprising 776 participants were included in the meta-analysis. HCD supplementation (anserine/carnosine, l-carnosine, β-alanine) caused a significant reduction in depression scores measured with the Becks Depression Inventory (-0.79; 95% CI: -1.24, -0.35; moderate certainty on GRADE) when compared with placebo. An increase in quality-of-life scores measured with the 36-item Short-Form survey (SF-36) (0.65; 95% CI: 0.00, 1.30) and low certainty on GRADE in HCDs (anserine/carnosine, l-carnosine, β-alanine) when compared with placebo were found. However, the rest of the outcomes did not show a significant change between HCD supplementation and placebo. Although the number of studies included in the meta-analysis was modest, a significant mean reduction was observed in depression score as well as an increase in quality-of-life score for the HCD group when compared with placebo. Most of the studies included had small sample sizes with short follow-up periods and moderate to high risk of bias, highlighting the need for further, well-designed studies to improve the evidence base.

PROSPERO registration no. CRD42017075354.

A subset of major depressive disorder (MDD) is characterized by immune system dysfunction, but the intracellular origin of these immune changes remains unclear. Here we tested the hypothesis that abnormalities in endoplasmic reticulum (ER) stress, inflammasome activity and mitochondrial biogenesis contribute to the development of systemic inflammation in MDD. RT-qPCR was used to measure mRNA expression of key organellar genes from peripheral blood mononuclear cells (PBMCs) isolated from 186 MDD and 67 healthy control (HC) subjects. The comparative CT (2-ΔΔCT) method was applied to quantify mRNA expression using GAPDH as the reference gene. After controlling for age, sex, BMI, and medication status using linear regression models, expression of the inflammasome (NLRC4 and NLRP3) and the ER stress (XBP1u, XBP1s, and ATF4) genes was found to be significantly increased in the MDD versus the HC group. Sensitivity analyses excluding covariates yielded similar results. After excluding outliers, expression of the inflammasome genes was no longer statistically significant but expression of the ER stress genes (XBP1u, XBP1s, and ATF4) remained significant and the mitochondrial biogenesis gene, MFN2, was significantly increased in the MDD group. NLRC4 and MFN2 were positively correlated with serum C-reactive protein concentrations, while ASC trended significant. The altered expression of inflammasome activation, ER stress, and mitochondrial biogenesis pathway components suggest that dysfunction of these organelles may play a role in the pathogenesis of MDD.

Several studies suggest a bidirectional association between inflammation, and anxiety and depression. Elevated inflammatory cytokines generate and aggravate neuroinflammation, which may play a part in developing psychological symptoms. Growth differentiation factor 15 (GDF-15) is a novel biomarker possibly reflecting fibrosis and inflammation. The aim of the current study was to investigate the associations between levels of GDF-15 and symptoms of anxiety and depression in the general population.

We measured GDF-15 in middle-aged persons participating in the Akershus Cardiac Examination 1950 Study. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), with HADS ≥8 denoting significant symptoms. We used multivariable regression analysis to assess the associations between GDF-15 and HADS, adjusting for levels of C-reactive protein (CRP), demographics, and comorbidities.

A total of 3638 participants had valid assessment of HADS and measurements of GDF-15 and CRP. The mean age was 63.9 (SD 0.65) years, and 48.8% were women. In adjusted models, levels of GDF-15 were associated with the continuous HADS-D score (β = 0.27, 95% confidence interval [CI] = 0.12 to 0.43) and HADS-D score ≥8 (odds ratio = 1.41, 95% CI = 1.12 to 1.78), but not with the continuous HADS-A score (β = 0.06, 95% CI = -0.12 to 0.24) or HADS-A score ≥8 (odds ratio = 1.06, 95% CI = 0.88 to 1.27).

Levels of GDF-15 are independently associated with symptoms of depression in the general population. Our results reinforce the notion that inflammation may be a contributing factor for the development of clinical depression.

ClinicalTrials.gov identifier NCT01555411 (Akershus Cardiac Examination [ACE] 1950 Study), https://clinicaltrials.gov/study/NCT01555411.