Evidence on whether systemic inflammation mediates the association between diet and depression and anxiety is lacking.

We analyzed 55,799 participants from the UK Biobank, assessing dietary inflammatory index (DII) based on 3 days' 24-hour dietary recall. Systemic inflammation was represented by systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI). Incident depression and anxiety were ascertained through linkage to hospital records, and Cox proportional hazard regression models evaluated the associations, with mediation analysis performed for systemic inflammation.

DII ranged from -6.87 to 4.88 with a median of -0.67. After a median follow-up time of 9.12 years, 1409 were diagnosed with depression and 1806 with anxiety. Higher DII level is associated with the incident risk of depression (HRQ4vsQ1 = 1.20, 1.09-1.32, P < 0.001) and anxiety (HRQ4vsQ1 = 1.10, 1.00-1.21, P < 0.001). SIRI and SII respectively mediate 4.12 % (95 % CI = 1.30 %-23.3 %, P < 0.001) and 4.43 % (95 % CI = 1.89 %-43.75 %, P < 0.001) of the association between DII and depression incidence. As for anxiety, SIRI mediated 8.27 % (95 % CI = 1.44 %-15.31 %, P < 0.001) and SII mediated 4.19 % (95 % CI = 1.58 %-11.47 %, P < 0.001), respectively.

The potential coexistence of anxiety and depression with other psychiatric disorders and limitations in data on changes in DII and inflammation markers over time may bias the findings. The study's generalization is constrained by the demographic of participants.

Our findings suggest that DII is positively associated with depression and anxiety, which may be mediated by SII/SIRI.

Existing evidence on the relationship between parity and women's later-life depression was inconsistent. We aimed to examine the association of parity with depression in women's mid-late life, and to evaluate whether such association differs by socioeconomic status (SES). We used data of 9508 women from two nationally representative cohort studies: China Health and Retirement Longitudinal Study and US Health and Retirement Study. Participants were followed up from 2011 or 2012 (baseline) to 2018. Parity was the number of biological children; depression symptoms were measured using Center for Epidemiologic Studies Depression Scale. Logistic regression models were used to assess the association between parity status and depression. A total of 4291 women had depression at baseline, and 1804 women developed depression during follow-up. Compared to women with one child, those with no children had higher odds of baseline depression (odds ratio [OR] = 1.25, 95 % confidence interval [CI] = 1.00-1.56) and developing depression (OR = 1.98, 95 % CI = 1.41-2.79) during follow-up. For multiparous women, a higher parity was associated with higher prevalence and incidence of depression, with the odds of incident depression ranging from 1.49 (95 % CI = 1.22-1.82) to 1.86 (95 % CI = 1.47-2.34) for having two children to ≥4 children. Such associations were more evident among women with high and upper-middle SES, with the odds of incident depression increasing from 1.91 (95 % CI = 1.45-2.51) for women with two children to 2.65 (95 % CI = 1.87-3.78) for women with ≥4 children. However, these associations were not observed among women in low and lower-middle SES group. Our findings underscore that healthcare practice should consider reproductive histories and social context when addressing women's mental health issues.

Although adverse childhood experiences (ACEs) are commonly associated with depressive symptoms in adulthood, studies frequently collapse ACEs into a single unitary index, making it difficult to identify specific targets for intervention and prevention. Furthermore, studies rarely explore sex differences in this area despite males and females often differing in the experiences of ACEs, depressive symptoms, and inflammatory activity. To address these issues, we used data from the National Longitudinal Study of Adolescent to Adult Health to model the effects of 10 different ACEs on C-reactive protein (CRP) and depressive symptoms in adulthood. Path modeling was used to measure the effects of ACEs on CRP and depressive symptoms conjointly while also assigning covariances among ACEs to assess their interrelations. Sex-by-ACE interaction terms and sex-disaggregated models were used to test for potential differences. Emotional abuse and parental incarceration were consistently related to both CRP and depressive symptoms for males and females. Childhood maltreatment was associated with depressive symptoms for females, whereas sexual abuse was associated with inflammation for males. Several covariances among ACEs were identified, indicating potential networks through which ACEs are indirectly associated with CRP and depressive symptoms. These data demonstrate that ACEs have differing direct effects on CRP and depressive symptoms - and that they differ with respect to how they cluster - for males versus females. These differences should be considered in theory and clinical workflows aiming to understand, treat, and prevent the long-term impacts of ACEs on depressive symptoms and inflammation-related health conditions in adulthood.

Post-COVID syndrome has unveiled intricate connections between inflammation, depressive psychopathology, and cognitive impairment. This study investigates these relationships in 101 COVID-19 survivors, focusing on sex-specific variations. Utilizing path modelling techniques, we analyzed the interplay of a one-month 48-biomarker inflammatory panel, with three-months of depressive symptoms and cognitive performance. The findings indicate that cognitive impairment is influenced by both inflammation and depression in the overall cohort. However, prominent sex-specific differences emerged. In females, a lingering imbalance between pro- and anti-inflammatory responses-likely reflecting the long-lasting immune alterations triggered by COVID-19-significantly affects cognitive functioning and shows a marginal, though not statistically significant, association with depressive symptoms. This suggests that a mixed inflammatory profile may contribute to these outcomes. Conversely, in males, inflammation was inversely associated with depression severity, with protective effects from regulatory mediators (IL-2, IL-4, IL-6, IL-15, LIF, TNF-α, β-NGF) against depression. In males, cognitive impairment appeared to be driven mainly by depressive symptoms, with minimal influence from inflammatory markers. These results highlight distinct sex-specific pathways in immune and inflammatory responses post-COVID-19, potentially shaped by endocrine mechanisms. The findings suggest that persistent inflammation may foster long-term neuropsychiatric sequelae, possibly through its effects on the brain, and underscore the need for sex-tailored therapeutic strategies to address the lasting impact of COVID-19.

Luteolin is a natural flavonoid compound exists in various fruits and vegetables. Recent studies have indicated that luteolin has variety pharmacological effects, including a wide range of antidepressant properties. Here, we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power. Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin. Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets. The antidepressant effects of luteolin may involve promoting intracellular noradrenaline (NE) uptake; inhibiting 5-hydroxytryptamine (5-HT) reuptake; upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione S-transferase; and decreasing the expression of malondialdehyde, caspase-3, and amyloid-beta peptides. The antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic-pituitary-adrenal axis regulation, and 5-HT metabolism. Additionally, we identified insulin-like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor alpha (ESR1), and epidermal growth factor receptor (EGFR) as potential targets, luteolin has an ideal affinity for these targets, suggesting that it may play a positive role in depression through multiple targets, mechanisms, and pathways. However, the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.

Evidence suggests a bidirectional association between psoriasis and depression, which is considered to reflect complex neuroimmunological and psychosocial interactions. Despite an early interest in the brain-skin axis and the role of stress in psoriasis immunopathogenesis, there is ongoing limited preclinical and clinical research into the inflammatory links between depression and psoriasis. Existing findings for serum inflammatory markers of depression in psoriasis are inconsistent and do not fully align with those in the general population, while brain imaging evidence is scarce and has not confirmed direct brain involvement in the systemic inflammation of psoriasis. The present paper reviews the available literature on the immune interplay of psoriasis with depression, highlights the significance of further work in the field and proposes avenues for future research.

The long-term effects of ischemic stroke on cognition and mental health are not reflected in traditional outcome metrics, like the modified Rankin Scale (mRS) for functional independence. Consequently, this may lead to mismatches in perceptions of overall recovery, despite otherwise qualifying as having good functional outcomes (mRS 0-2). In our multicenter, multinational analysis, we aim to describe the prevalence of, and factors associated with, patient-reported cognitive impairment despite achieving good functional outcomes. Acute ischemic stroke patients at Cooper University Hospital (2021-2024) and Hospital Vall d'Hebron in Barcelona, Spain (2020-2021) treated with reperfusion therapy and achieved 90-day mRS 0-2 were surveyed with the previously-validated PROMIS Global-10 scale for physical health (PROMIS-PH) and mental health (PROMIS-MH). The primary outcome was the rate of fair or poor PROMIS-MH scores (≤ 11). Univariable and multivariable linear regressions for PROMIS-MH scores were performed. Of 157, 90-day mRS 0-2 patients, the mean age was 68 (standard deviation 15) years, and 61 % were male. Fair or poor PROMIS-MH scores were reported in 43 % of patients. Clinical factors independently associated with PROMIS-MH scores in a multivariable linear regression include: sex, tobacco use, PROMIS-PH score, and National Institutes of Health Stroke Scale at 3-day follow-up. Despite achieving favorable post-stroke mRS, there is a high prevalence of patient-reported cognitive impairment, underscoring an important gap in post-stroke care. The emphasis in post-stroke care should extend beyond the scope of traditional metrics, and should encompass evaluations and interventions targeting additional domains significant to overall patient recovery, especially patient-reported cognitive symptoms.

During pregnancy and the postpartum, there are dynamic fluctuations in steroid and peptide hormone levels as well as inflammatory signalling. These changes are required for a healthy pregnancy and can persist well beyond the postpartum. Many of the same hormone and inflammatory signalling changes observed during the perinatal period also play a role in symptoms related to autoimmune disorders, psychiatric disorders, and perhaps neurodegenerative disease later in life. In this review, we outline hormonal and immunological shifts linked to pregnancy and the postpartum and discuss the possible role of these shifts in increasing psychiatric, neurodegenerative disease risk and autoimmune symptoms during and following pregnancy. Furthermore, we discuss how key variables such as the number of births (parity) and sex of the fetus can influence inflammatory signalling, and possibly future disease risk, but are not often studied. We conclude by discussing the importance of studying female experiences such as pregnancy and parenting on physiology and disease.

The effect of interleukin-6 (IL-6) on cognition in patients with major depressive disorder (MDD) remains unclear. The aim of the present study was to investigate for the first time the non-linear relationship between plasma IL-6 and cognition and its sex-specific associations in patients with drug-naïve MDD.

A total of 326 participants, including 237 drug-naïve MDD patients and 89 healthy controls (HCs), were included in this study. All participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and fasting venous blood was collected for IL-6 measurement. Patients with MDD completed the Hamilton Depression Scale-17 (HAMD-17) and the Hamilton Anxiety Scale-14 (HAMA-14) assessments. Two-way analysis of variance and curve estimation analyses were used to explore the effects of IL-6 on cognition and its sex differences.

We found that IL-6 and cognition were associated in different patterns in HCs and MDD patients. The best model for curve estimation between IL-6 and attention (F = 2.736, p = 0.045) and HAMA (F = 6.416, p < 0.001) in females with MDD was the cubic model. In male MDD patients, the best model for curve estimation between IL-6 and immediate memory was the cubic model (F = 3.077, p = 0.034). However, in HCs, the best model for curve estimation analysis between IL-6 and language was the quadratic model (F = 3.803, p = 0.026).

The main limitations were cross-sectional design.

There was a non-linear and sex-specific relationship between IL-6 levels and cognition in patients with MDD.

Previous research has linked systemic inflammatory markers and the Dietary Inflammatory Index (DII) with depression. However, the relationship between DII and these markers, and their impact on mortality risk among depressed adults, remains underexplored. This study aims to explore the association between DII and systemic inflammatory markers and their mediating effect on mortality risk in adults with depression.

This study analyzed data from 4,981 adults with depression in the National Health and Nutrition Examination Survey (NHANES). This study quantified dietary inflammatory potential with the DII and systemic inflammation with the Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI). Cox proportional hazards regression and inverse probability weighting evaluated the impact of DII, SII, and SIRI on mortality risk in depressed adults, as well as their mediating effects. Multiple linear regression analyzed the associations between DII and SII/SIRI. Restricted cubic spline analysis explored the non-linear relationship between DII and mortality risk.

In adjusted regression models, DII, SII, and SIRI were significantly associated with all-cause mortality risk in depressed adults, with hazard ratios (HRs) (95% CIs) from 1.333 to 1.497 (1.051-1.233, 1.689-1.832). DII was linearly related to SII, with βs (95% CIs) from 0.001 to 0.121 (0.001-0.017, 0.001-0.224). SII significantly mediated the DII-mortality risk link, especially in males (8.07%). The DII-mortality relationship was linear (P non-linear = 0.174), with a beneficial threshold at 1.62.

DII and SII are associated with increased all-cause mortality risk in depressed adults. The DII-related mortality risk in depression can be partially mediated by SII, with a more pronounced effect in males.

Loneliness and depression are serious public mental health problems. Meaning in life (MIL) is associated with reduced loneliness and depression. This study aimed to: (1) investigate associations between loneliness, MIL, and depression, differentiated by sex in individuals aged ≥ 50 years, residing in 26 European countries and Israel, and (2) to examine in men and women separately whether MIL mediated the relationship between loneliness and depression. We included 41,372 individuals (23,789 women) who responded to wave 8 of the SHARE project. The variables analyzed were loneliness (UCLA), depression (EURO-D scale), and MIL (CASP-19). The analytical procedures included regression analysis and exploratory mediation analysis. Among men and women, the odds of loneliness increasing depression were 3.6 and 3.3 times higher, respectively. Among men, feeling MIL sometimes or often had odds for reducing depression by 0.53 and 0.21, respectively. In women, feeling MIL sometimes or frequently reduced the odds of depression by 0.37 and 0.19, respectively. Regardless of sex, mediation analyses showed a positive association between loneliness and depression, while MIL was negatively associated with loneliness and depression. MIL partially mediated the association between LON and depression in male and female models by approximately 83.2% and 80.7%, respectively. No differences were found between men's and women's mediation models. Regardless of sex, high levels of MIL seem to be effective in benefiting the mental health of Europeans aged 50 and over. MIL proved to be a significant mediator of the relationship between loneliness and depression, while loneliness and depression strengthened each other.

In the low-resource rural areas, older adults may experience prolonged and severe depressive symptoms. This study aimed to investigate the relationship between uric acid, depressive symptoms and immunoinflammatory among rural older adults.

This case-control study was conducted in 17 rural villages in Hunan Province, China, between January 2023 and April 2024. This study included 180 participants: (1) Rural Older Adults with Depressive Symptoms group:90 patients with first-time diagnosed with depressive symptoms (Geriatric Depression Scale-15, GDS-15 ≥ 5 scores); (2) Control group: 90 individually matched (age and sex) healthy subjects (GDS-15 < 5 scores) who were aged ≥60 years.

Both males and females, depressive symptoms were associated with higher uric acid levels and C-reactive protein levels (All P < 0.05). Whereas in females, depressive symptoms were also linked to higher procalcitonin (P = 0.005) and serum amyloid A (P = 0.008) levels. In addition, C-reactive protein plays a significant mediating role between uric acid and depressive symptoms in males.

Further investigation is necessary to clarify the underlying mechanisms, examine gender-specific disparities, and assess potential therapeutic interventions targeting uric acid and inflammation levels to mitigate mental disorders risk.

Psychoneuroimmunology (PNI) researchers can advance their careers and increase their scientific impact by prioritizing their writing skills. In addition to Dr. Kiecolt-Glaser's landmark research that inspired this special issue, her legacy is reflected in her prolific writing. Dr. Kiecolt-Glaser has the unique ability to convey her innovative research clearly and to diverse audiences. She also made writing mentorship a critical part of the training experience in her lab. In these ways, Dr. Kiecolt-Glaser's writing skills and mentorship have shaped both the PNI field and her trainees' careers. In this paper, I distill lessons learned about writing from Dr. Kiecolt-Glaser during my time as a graduate student in her Stress and Health Lab in the 2010s. I reflect on Dr. Kiecolt-Glaser's influence on her trainees' writing habits, summarize "writing pearls" inspired by her feedback/revisions, and provide observations on her writing mentorship habits. These tips are intended to help PNI trainees to clearly communicate their work and to help mentors reflect on ways they can prioritize and advance their trainees' writing skills. Finally, I reflect on how Dr. Kiecolt-Glaser's mentorship and scientific accomplishments had a tremendous impact on my own career development.

Major Depressive Disorder (MDD) is a heterogeneous disorder that affects twice as many women than men. Precluding advances in more tailored and efficacious treatments for depression is the lack of reliable biomarkers. While depression is linked to elevations in inflammatory immune system functioning, this relationship is not evident among all individuals with depression and may vary based on symptom subtypes and/or sex. This systematic review and meta-analysis examined whether inflammatory immune peripheral markers of depression are sex-specific. PRISMA guidelines were followed for the systematic review, and a comprehensive search strategy that identified studies from PubMed and PsycInfo was applied. Studies were included if they reported C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and/or IL-1β for males and/or females among depressed and healthy adults. We identified 23 studies that satisfied these inclusion criteria. Random-effects meta-analysis models were fit, and measures of association were summarized between levels of circulating markers of inflammation in depressed and healthy males and females. Sex-based analyses revealed elevated levels of CRP among females with depression (Cohen's d = 0.19) relative to their healthy counterparts (p = 0.02), an effect not apparent among males (Cohen's d = -0.01). Similarly, levels of IL-6 were increased among females with depression compared to healthy controls (Cohen's d = 0.51; p = 0.04), but once again this was not found among males (Cohen's d = 0.16). While TNF-α levels were elevated among individuals with depression compared to controls (p = 0.01), no statistically significant sex differences were found. The meta-analysis for IL-1β resulted in only three articles, and thus, results are presented in the supplemental section. This meta-analysis advances our understanding of the unique involvement of inflammatory biomarkers in depression among men and women, which may help inform more tailored sex-specific treatment approaches in the future.

Inflammation has been postulated as a mediating factor in the development of Alzheimer's disease (AD) pathology. We investigated candidate inflammatory markers related to conversion to AD among patients with depression.

A longitudinal study was conducted with older women with depression who were at least 55 years of age, with a mean follow-up period of 5.73 years. At baseline, 9 inflammatory cytokines were measured using the immunoreactivity method. During follow-up, patients with depression who complained of cognitive impairment were evaluated and diagnosed with AD conversion. Association of the cytokines with conversion to AD was analyzed using multivariable Cox proportional hazards regression with adjusting covariates. For clinical applicability, the optimal cutoff value was determined using the minimum p value approach for the conversion to AD and was used to plot an AD-free survival curve.

Among 132 participants, 34 patients with depression (25.76%) developed AD during their follow-up period. Higher levels of interleukin (IL) 1β at baseline (hazard ratio = 3.30 [95% CI, 1.11-9.78], p = .031) and lower levels of IL-10 (p < .001) were significantly associated with an increased risk of progression to AD. The survival curve plotted by the cutoff value of ≥0.25 pg/mL for IL-1β and ≤0.15 pg/mL for IL-10 suggested adjusted hazard ratios of 8.96 (95% CI, 3.48-23.09; p < .001) for IL-1β and 10.99 (p < .001) for IL-10, respectively.

This study demonstrated that IL-1β and IL-10 were associated with conversion to AD among patients with late-life depression, suggesting their potential as predictive markers of the transition to AD from depression.

In the older population, depression, loneliness, and quality of life are closely related, significantly influencing health status. This paper aimed (1) to investigate autoregressive and cross-lagged associations over 2 years between depression, loneliness, and quality of life, and (2) to examine sex-related differences in the 2-year associations between depression, loneliness, and quality of life in a large sample of European citizens aged ≥ 50 years.

This is a longitudinal analysis. We included 7.456 individuals (70.89 ± 7.64 years; (4.268 females) who responded to waves 7 (2017) and 8 (2019) of the SHARE project. The variables analyzed in both waves were depression, loneliness, and quality of life.

Comparatively, females indicated higher depression and loneliness scores than males and a lower perception of quality of life. Autoregressive associations pointed that past depression, loneliness, and quality of life predicted their future episodes 2 years later (p < 0.001). The cross-lagged analysis of males showed positive and significant bidirectional associations between depression and loneliness 2 years later. Females also showed a positive and significant association between depression and loneliness, but loneliness was not associated with depression 2 years later. In turn, previous high levels of quality of life had a protective role in late depression and loneliness up to 2 years.

This study highlighted the need to simultaneously assess and manage depression, loneliness, and quality of life in the older European population. It is suggested that sex-specific policies can be created, including social support, in order to reduce depression and loneliness, and promote quality of life.

In recent years, the incidence of abdominal obesity among the middle-aged and older adult population in China has significantly increased. However, the gender disparities in the spatial distribution of abdominal obesity incidence and its relationship with meteorological factors among this demographic in China remain unclear. This gap in knowledge highlights the need for further research to understand these dynamics and inform targeted public health strategies.

This study utilized data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) to analyze the incidence of abdominal obesity among the middle-aged and older adult population in China. Additionally, meteorological data were collected from the National Meteorological Information Center. Using Moran's I index and Getis-Ord Gi* statistical methods, the spatial distribution characteristics of abdominal obesity incidence were examined. The influence of various meteorological factors on the incidence of abdominal obesity in middle-aged and older adult males and females was investigated using the q statistic from the Geodetector method. Furthermore, Multi-Scale Geographically Weighted Regression (MGWR) analysis was employed to explore the impact of meteorological factors on the spatial heterogeneity of abdominal obesity incidence from a gender perspective.

The spatial distribution of abdominal obesity among middle-aged and older adult individuals in China exhibits a decreasing trend from northwest to southeast, with notable spatial autocorrelation. Hotspots are concentrated in North and Northeast China, while cold spots are observed in Southwest China. Gender differences have minimal impact on spatial clustering characteristics. Meteorological factors, including temperature, sunlight, precipitation, wind speed, humidity, and atmospheric pressure, influence incidence rates. Notably, temperature and sunlight exert a greater impact on females, while wind speed has a reduced effect. Interactions among various meteorological factors generally demonstrate bivariate enhancement without significant gender disparities. However, gender disparities are evident in the influence of specific meteorological variables such as annual maximum, average, and minimum temperatures, as well as sunlight duration and precipitation, on the spatial heterogeneity of abdominal obesity incidence.

Meteorological factors show a significant association with abdominal obesity prevalence in middle-aged and older adults, with temperature factors playing a prominent role. However, this relationship is influenced by gender differences and spatial heterogeneity. These findings suggest that effective public health policies should be not only gender-sensitive but also locally adapted.

An association between insulin resistance (IR) and depression has been identified in recent years. The purpose of this study was to examine the relationship between IR and depression in the general population.

The population for this cross-sectional study consisted of adults participating in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Insulin sensitivity was assessed using the Metabolic Score for IR (METS-IR) index, while depression was evaluated using the Patient Health Questionnaire (PHQ)-9. Logistic regression analyses, subgroup analyses, and dose-response curves were conducted to assess the association between the METS-IR index and depression.

A total of 13,157 adults aged over 20 years were included in this study. After adjusting for potential confounders, it was observed that each unit increase in the METS-IR index was associated with a 1.1 percentage point increase in the prevalence of depression (OR = 1.011; 95 % CI: 1.008, 1.014). Patients in the 4th quartile of the METS-IR index had a higher likelihood of depression compared to those in the 1st quartile (OR = 1.386, 95 % CI: 1.239, 1.549). Stratified analyses demonstrated consistent results in all subgroups, except for men, patients under 40 years of age, and those with a history of cancer. Dose-response curves indicated a nonlinear relationship between the METS-IR index and the risk of depression, with an inflection point value of 32.443 according to threshold effect analysis.

Our findings suggest that higher METS-IR scores are associated with an increased likelihood of experiencing depressive symptoms among U.S. adults.

This study examined the extent to which adolescent peer victimization predicted acute inflammatory responses to stress, and whether both resting parasympathetic nervous system (PNS) activity and PNS stress reactivity moderated this association. 83 adolescents (Mage = 14.89, SDage = 0.52, 48% female) reported their history of peer victimization and were exposed to a standardized social stress task before and after which dried blood spot samples were collected to assay inflammatory markers. Inflammatory responses to the stress task were assessed with a latent inflammatory change factor using the cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). PNS functioning, indexed by high-frequency heart rate variability, was measured at rest and during the stressor. Contrary to hypotheses, analyses revealed no direct relation between peer victimization and acute inflammatory responses, and resting PNS activity did not moderate this association. However, peer victimization predicted stronger inflammatory responses among adolescents with weaker PNS reactivity to the stress task (b = 0.63, p = .02). This association was not observed among adolescents with stronger PNS reactivity, for whom a negative but non-significant trend was found. Weaker PNS reactivity may thus indicate victimized adolescents' vulnerability for acute inflammatory responses, whereas stronger PNS reactivity may indicate adolescents' resilience to a social stressor.

Although females are at relatively greater risk for a variety of disorders, including depression, the biological mechanisms underlying this striking health disparity remain unclear. To address this issue, we highlight sex differences in stress susceptibility as a key mechanism potentially driving this effect and describe the interacting inflammatory, hormonal, epigenomic, and social-environmental mechanisms involved.

Using the Social Signal Transduction Theory of Depression as a theoretical framework, women's elevated risk for depression may stem from a tight link between life stress, inflammation, and depression in women. Further, research finds hormonal contraceptive use alters cortisol and inflammatory reactivity to acute stress in ways that may increase depression risk in females. Finally, beyond established epigenetic mechanisms, mothers may transfer risk for depression to their female offspring through stressful family environments, which influence stress generation and stress-related gene expression. Together, these findings provide initial, biologically plausible clues that may help explain the relatively greater risk for depression in females vs. males. Looking forward, much more research is needed to address the longstanding underrepresentation of females in biomedical research on the biology of stress and depression.

Inflammation can play a role in the pathophysiology of depression, and specific types of antidepressants may have inflammatory or anti-inflammatory properties. Furthermore, depression and antidepressant use has been linked to white blood cell (WBC) count, a routinely measured inflammatory marker. We examined the cross-sectional and longitudinal relationships of depressive symptoms and/or antidepressant use with WBC count among postmenopausal women. Analyses of cross-sectional data at enrollment were performed on 125,307 participants, 50-79 years of age, from the Women's Health Initiative Clinical Trials and Observational Studies who met eligibility criteria, and a subset of those with 3-year follow-up data were examined for longitudinal relationships. Depressive symptoms were defined using the Burnam Algorithm whereas antidepressant use was defined using therapeutic class codes. WBC count (Kcell/ml) was obtained through laboratory evaluations of fasting blood samples. Multivariable regression modeling was performed taking sociodemographic, lifestyle and health characteristics into consideration. At enrollment, nearly 85% were non-users of antidepressants with no depressive symptoms, 5% were antidepressant users with no depressive symptoms, 9% were non-users of antidepressants with depressive symptoms, and 2% were users of antidepressants with depressive symptoms. In fully-adjusted models, cross-sectional relationships were observed whereby women in the 2nd (OR = 1.06, 95% CI: 1.01, 1.13), 3rd (OR = 1.06, 95% CI: 1.00, 1.12) or 4th (OR = 1.10, 95% CI: 1.05, 1.17) quartiles of WBC count were more likely to exhibit depressive symptoms, and women in the 4th quartile were more likely to be users of antidepressants (OR = 1.07, 95% CI: 1.00, 1.15), compared to women in the 1st quartile. Compared to women who exhibited no depressive symptoms at either visit, those with consistent depressive symptoms at enrollment and at 3-year follow-up had faster decline in WBC count (β = -0.73, 95% CI: -1.33, -0.14) over time. No significant bidirectional relationships were observed between changes in depressive symptoms score and WBC count over time. In conclusion, depressive symptoms and/or antidepressant use were cross-sectionally related to higher WBC counts among postmenopausal women. Further evaluation of observed relationships is needed in the context of prospective cohort studies involving older adult men and women, with repeated measures of depression, antidepressant use, and WBC count.

C-reactive protein serves as a marker of inflammation and is linked to depression in the general population. We aimed to assess whether elevated baseline levels of high-sensitivity C-reactive protein (hs-CRP) are associated with depressive symptoms over time in a prospective cohort of mild-to-moderate first-ever ischemic stroke patients.

Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) at three annual follow-up points. We assessed the association of elevated levels of hs-CRP with CES-D scores over time via linear mixed models. In a subgroup analysis, we explored an interaction effect with sex.

We included 585 ischemic stroke patients with baseline data on CRP levels. The mean age was 67 (13 SD), 39% (n = 226) were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 3 (IQR 1-4). Twenty percent of survivors showed evidence for depressive symptoms one year after stroke with CES-D ≥ 16, 21% at year two, and 17% at year three. Higher log-transformed baseline hs-CRP levels were associated with higher CES-D Scores over time in the adjusted linear mixed model (β = 1.28; (95% CI 0.22-2.34)). The subgroup analysis revealed an interaction effect of hs-CRP on depressive symptoms in women (β = 2.33; (95% CI 0.71-3.95)).

In our cohort with mild-to-moderate first-ever ischemic stroke patients, hs-CRP levels were associated with more depressive symptoms over time, with an interaction effect for the female sex.

https://clinicaltrials.gov ; Unique identifier: NCT01363856.

Dietary fatty acids are related to the development of several inflammatory-related diseases, which may include depression. So, the association between fatty acids, culinary oils and fat intake and depression in highly educated Brazilians was evaluated.

Multicenter cross-sectional study using baseline data from the Cohort of Universities of Minas Gerais. The diagnosis of depression was self-reported, and the daily intake of fatty acids was assessed using a 144-item food frequency questionnaire (FFQ).

A total of 7157 participants (68.83 % women) with a median age of 33 years were included. The prevalence of depression was 12.60 % (N = 902). In the adjusted analyses, it was observed that individuals with the highest intake of omega-6 fatty acids (n-6) (OR: 1.36, 95 % CI 1.11-1.67) had a higher prevalence of depression. This increased n-6 intake was identified as a risk factor for depression only among male participants, while among overweight participants, higher n-6 intake was also positively associated with depression. Conversely, a higher ratio of polyunsaturated to monounsaturated and saturated fatty acids (PM/S) was also found to be positively associated with depression, but this association was observed only among non-overweight participants. No associations were found between the consumption of culinary oils or fats and depression.

Cross-sectional design limits the assessment of causality. The use of the FFQ can make estimates more difficult.

Higher consumption of n-6, and higher PM/S ratios were associated with depression, and individual factors can interfere. The mental health care policies should include specific nutritional strategies.

Dementia caregiving has been linked to multiple health risks, including infectious illness, depression, anxiety, immune dysregulation, weakened vaccine responses, slow wound healing, hypertension, cardiovascular disease, metabolic syndrome, diabetes, frailty, cognitive decline, and reduced structural and functional integrity of the brain. The sustained overproduction of proinflammatory cytokines is a key pathway behind many of these risks. However, contrasting findings suggest that some forms of caregiving may have beneficial effects, such as maintaining caregivers' health and providing a sense of meaning and purpose which, in turn, may contribute to lower rates of functional decline and mortality. The current review synthesizes these disparate literatures, identifies methodological sources of discrepancy, and integrates caregiver research with work on aging biomarkers to propose a research agenda that traces the mechanistic pathways of caregivers' health trajectories with a focus on the unique stressors facing spousal caregivers as compared to other informal caregivers. Combined with a focus on psychosocial moderators and mechanisms, studies using state-of-the-art molecular aging biomarkers such as telomere length, p16INK4a, and epigenetic age could help to reconcile mixed literature on caregiving's sequelae by determining whether and under what conditions caregiving-related experiences contribute to faster aging, in part through inflammatory biology. The biomarkers predict morbidity and mortality, and each contributes non-redundant information about age-related molecular changes -together painting a more complete picture of biological aging. Indeed, assessing changes in these biopsychosocial mechanisms over time would help to clarify the dynamic relationships between caregiving experiences, psychological states, immune function, and aging.

Several factors may affect response to treatment in Major Depressive Disorder (MDD) including immune/inflammatory alterations and regional brain volumes, particularly in hippocampal regions which have shown to be influenced by inflammatory status. Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker found to be elevated in depressed women in large population studies. Here we investigate the effect of NLR on treatment response in MDD patients, and the role of sex and hippocampal volume on influencing this relationship. A sample of 124 MDD depressed inpatients (F = 80) underwent MRI acquisition, admission NLR was calculated by dividing absolute neutrophil by absolute lymphocyte counts and depression severity was assessed at admission and discharge via the Hamilton Depression Rating Scale (HDRS). As a measure of treatment response, delta HDRS was calculated. We found a significant moderation effect of sex on the relationship between NLR and Delta HDRS: a negative relation was found in females and a positive one in males. NLR was found to negatively affect hippocampal volumes in females. Both left and right hippocampal volume positively associated with Delta HDRS. Finally, left hippocampal volume mediated the effect of NLR on Delta HDRS in females. Sex moderated the relation between inflammation and treatment response in line with previous reports linking inflammation to hampered antidepressant effect in females. Further, this effect is partially mediated by hippocampal volume, suggesting that antidepressant response may be hampered by the detrimental effect of inflammation on the brain.

Obesity and depression, disorders associated with inflammation, have high incidences in women. Understanding the derangements present in the initial phase of obesity may point to factors that could help avoiding disease aggravation. The present study aimed at investigating the effects of a 6-months interdisciplinary therapy for weight loss in women with grade I obesity. Before and after the therapy, 37 middle-aged women donated blood and responded to questionnaires for depression and anxiety symptoms. Inflammatory parameters were evaluated in serum and a preliminary screening of the plasma proteome was performed. The therapy decreased anthropometric, psychological scores, and serum levels of inflammatory parameters. Depression and anxiety scores correlated positively with some inflammatory parameters. The proteomic analysis showed changes in proteins related to cholesterol metabolism and inflammatory response. Interdisciplinary therapy improves anthropometric and inflammatory statuses and ameliorating psychological symptoms. The decrease of MCP-1 levels after interdisciplinary therapy has not been reported so far, at the best of our knowledge. The present demonstration of positive associations of inflammatory markers and psychological scores indicate that these mediators may be useful to monitor psychological status in obesity. The present proteome data, although preliminary, pointed to plasma alterations indicative of improvement of inflammation after interdisciplinary therapy.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression-another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein-a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239-246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.

It is largely unknown whether the gut microbiome regulates immune responses in humans. We determined relationships between the microbiota composition and immunological phenotypes in 108 healthy volunteers, using 16S sequencing, an ex vivo monocyte challenge model, and an in vivo challenge model of systemic inflammation induced by lipopolysaccharide (LPS).

Significant associations were observed between the microbiota composition and ex vivo monocytic cytokine responses induced by several stimuli, most notably IL-10 production induced by Pam3Cys, Pseudomonas aeruginosa and Candida albicans, although the explained variance was rather low (0.3-4.8%). Furthermore, a number of pairwise correlations between Blautia, Bacteroides and Prevotella genera and cytokine production induced by these stimuli were identified. LPS administration induced a profound transient in vivo inflammatory response. A second LPS challenge one week after the first resulted in a severely blunted response, reflecting endotoxin tolerance. However, no significant relationships between microbiota composition and in vivo parameters of inflammation or tolerance were found (explained variance ranging from 0.4 to 1.5%, ns).

The gut microbiota composition explains a limited degree of variance in ex vivo monocytic cytokine responses to several pathogenic stimuli, but no relationships with the LPS-induced in vivo immune response or tolerance was observed.

Individuals respond differently to inflammation. Pain, sadness, and fatigue are common correlates of inflammation among breast cancer survivors. Stress may predict response intensity. This study tested whether breast cancer survivors with greater exposure to acute or chronic social or nonsocial stress had larger increases in pain, sadness, and fatigue during an acute inflammatory response. In total, 156 postmenopausal breast cancer survivors (ages 36-78 years, stage I-IIIA, 1-9 years posttreatment) were randomized to either a typhoid vaccine/saline placebo or the placebo/vaccine sequence, which they received at 2 separate visits at least 1 month apart. Survivors had their blood drawn every 90 minutes for the next 8 hours postinjection to assess levels of interleukin-6 and interleukin-1 receptor antagonist (IL-1Ra). Shortly after each blood draw, they rated their current levels of pain, sadness, and fatigue. Women also completed the Test of Negative Social Exchange to assess chronic social stress and the Trier Inventory of Chronic Stressors screen to index chronic general stress. At each visit, a trained experimenter administered the Daily Inventory of Stressful Events to assess social and nonsocial stress exposure within the past 24 hours. After statistical adjustment for relevant demographic and behavioral covariates, the most consistent results were that survivors who reported more chronic social stress reported more pain and sadness in response to IL-1Ra increases. Frequent and ongoing social stress may sensitize the nervous system to the effects of inflammation, with potential implications for chronic pain and depression risk among breast cancer survivors.

Both depression and sleep disturbance have been linked to inflammation. However, the role that inflammation plays in the relationship between sleep disturbance and depression remains unclear. We examined pairwise associations between inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and C-reactive protein level [CRP]), sleep disturbance, and depressive symptoms in a robust, ethnically diverse sample (n = 32,749) from the National Health and Nutrition Examination Survey (NHANES). We found higher levels of inflammatory markers in participants with depression and/or sleep disturbance compared to those without depression or sleep disturbance. Sleep disturbance was positively associated with inflammatory markers and depressive symptoms even after considering a wide range of potential confounders (e.g., age, sex, body mass index). Inflammatory marker levels were nonlinearly associated with depressive symptoms and were positively associated with depressive symptoms after reaching the inflection point (NLR, 1.67; CRP, 0.22 mg/dL). Inflammatory markers mediated a marginal portion (NLR, 0.0362%, p = 0.026; CRP, 0.0678%; p = 0.018) of the potential effects of sleep disturbance on depressive symptoms. Our research showed that inflammatory markers, sleep disturbance, and depression are pairwise correlated. Increased inflammatory markers levels slightly mediate the association between sleep disturbance and depression.

Major depressive disorder is one of the major contributors to disability worldwide with an estimated prevalence of 4%. Depression is a heterogeneous disease often characterized by an undefined pathogenesis and multifactorial phenotype that complicate diagnosis and follow-up. Translational research and identification of objective biomarkers including inflammation can assist clinicians in diagnosing depression and disease progression. Investigating inflammation markers using machine learning methods combines recent understanding of the pathogenesis of depression associated with inflammatory changes as part of chronic disease progression that aims to highlight complex interactions. In this paper, 721 patients attending a diabetes health screening clinic (DiabHealth) were classified into no depression (none) to minimal depression (none-minimal), mild depression, and moderate to severe depression (moderate-severe) based on the Patient Health Questionnaire (PHQ-9). Logistic Regression, K-nearest Neighbors, Support Vector Machine, Random Forest, Multi-layer Perceptron, and Extreme Gradient Boosting were applied and compared to predict depression level from inflammatory marker data that included C-reactive protein (CRP), Interleukin (IL)-6, IL-1β, IL-10, Complement Component 5a (C5a), D-Dimer, Monocyte Chemoattractant Protein (MCP)-1, and Insulin-like Growth Factor (IGF)-1. MCP-1 and IL-1β were the most significant inflammatory markers for the classification performance of depression level. Extreme Gradient Boosting outperformed the models achieving the highest accuracy and Area Under the Receiver Operator Curve (AUC) of 0.89 and 0.95, respectively.Clinical Relevance- The findings of this study show the potential of machine learning models to aid in clinical practice, leading to a more objective assessment of depression level based on the involvement of MCP-1 and IL-1β inflammatory markers with disease progression.

Depression is more common in patients with chronic inflammatory diseases, but whether inflammatory bowel disease (IBD), a chronic, relapsing immune-mediated disease, is associated with a higher risk of depression remains uncertain.

We studied 497,134 participants in the UK Biobank, including 3561 IBD patients. Multivariate Cox proportional risk models were constructed to investigate the risk associated with IBD and depression adjusting for potential confounding factors including sociodemographic, lifestyle, and family history variables.

The average age of participants was 56.54 ± 8.09 years; 54.3% were female and 90.4% were white. Over a mean follow-up period of 13.3 years, the cumulative incidence of depression was 8.2% (95% CI: 7.3%-9.1%) in IBD patients compared with 4.9% (95% CI: 4.9%-5.0%) in individuals without IBD. Compared with non-IBD participants, the adjusted hazard ratio (HR) for depression among IBD patients was 1.56 (95% CI: 1.39-1.76), with an adjusted HR of 1.54 (95% CI: 1.25-1.90) in Crohn's disease and 1.52 (95% CI: 1.30-1.78) in ulcerative colitis, respectively.

IBD patients had a significantly higher risk of depression than non-IBD participants after adjusting for multiple confounding factors. We recommend screening for depression in middle-aged adults with IBD and no established history of depression.

Myocardial infarction, stroke, mental disorders, neurodegenerative processes, autoimmune diseases, cancer and the human immunodeficiency virus impact the haematopoietic system, which through immunity and inflammation may aggravate pre-existing atherosclerosis. The interplay between the haematopoietic system and its modulation of atherosclerosis has been studied by imaging the cardiovascular system and the activation of haematopoietic organs via scanners integrating positron emission tomography and resonance imaging (PET/MRI). In this Perspective, we review the applicability of integrated whole-body PET/MRI for the study of immune-mediated phenomena associated with haematopoietic activity and cardiovascular disease, and discuss the translational opportunities and challenges of the technology.

Major depressive disorder (MDD) is associated with dysfunctional self-reported interoception (i.e., abnormal perception of the body's physiological state) and systemic inflammation, both of which adversely affect treatment response. In this study, we explored associations between C-reactive protein (CRP) and self-reported interoception, to gain more insight into the pathophysiology of interoceptive impairments in MDD. We also aimed to replicate previous findings on the associations of depression and fatigue severity with CRP. The study included 97 depressed individuals, who completed self-administered questionnaires (Multidimensional Assessment of Interoceptive Awareness (MAIA-2); Beck Depression Inventory-II, Multidimensional Fatigue Inventory). CRP concentrations were analyzed in the serum using a particle-enhanced turbidimetric immunoassay. We applied Bayesian inference to estimate robust effect parameters from posterior distributions based on MCMC sampling, and computed Bayes factors (BF₁₀) as indices of relative evidence. The bivariate analysis supported evidence against associations between CRP and self-reported interoception (BF₁₀ ≤ 0.32), except for one dimension (Not-Distracting: r = 0.11, BF₁₀ > 0.43, absence of evidence). Positive correlations with overall depression (r = 0.21, BF₁₀ = 3.19), physical fatigue (r = 0.28, BF₁₀ = 20.64), and reduced activity (r = 0.22, BF₁₀ = 4.67) were found. The multivariate analysis showed moderate evidence that low-grade inflammation predicted higher scores on the MAIA-2 Not-Worrying scale (β = 0.28, BF₁₀ = 3.97), after controlling for relevant confounders. Inflammatory responses, as measured by CRP, may not be involved in the pathophysiology of dysfunctional self-reported interoception. However, systemic low-grade inflammation could potentially exert a protective effect against worries about pain or discomfort sensations. An immunological involvement in interoceptive impairments cannot be ruled out until future studies considering additional biomarkers of inflammation replicate our findings.

Excessively released proinflammatory mediators from activated macrophages and lymphocytes may contribute to the etiology of depression. However, the relationship between lymphocytes and depression is not fully understood. Although women have higher depression risk than men, sex/gender differences in psychoneuroimmunological mechanisms are still unclear. To explore these two questions, chronic unpredictable mild stress (CUMS) was used to evaluate the changes in behaviors, inflammation and lymphocyte subtypes in adult male and female Wistar rats. Results show that CUMS increased anhedonia and anxiety-like behaviors, along with increased serum corticosterone, hippocampal pro-inflammatory factors, CD11b, IFN-γ, IL-6 and IL-17, but decreased CD4, CD25, CD4/CD8 ratio, GFAP, 5-hydroxytryptamine (5-HT) and NE concentrations, regardless of sex. There was no positive correlation between sucrose preference and blood CD4/CD8 ratio, but a positive correlation between sucrose preference and spleen CD25, sucrose preference and neurotransmitters (NE and 5-HT), spleen CD25 and serum TGF-β1/IL-6 ratio were found, regardless of sex. Females presented higher basal locomotion, blood CD4, CD4/CD8 ratio, serum corticosteroid and IL-6 concentrations, but lower hippocampal norepinephrine (NE) than males. Although CUMS didn't induce significant sex differences, females presented more changes in CD4 and CD8 lymphocytes than male rats. CUMS caused abnormalities in corticosteroid, lymphocytes, cytokines and neurotransmitters, which might be the precursors for inducing depression-like behaviors in both sexes.

We performed a meta-analysis and estimated the prevalence of depression and anxiety and their related factors among patients with chronic rhinosinusitis (CRS).

PubMed, Embase, Web of Science, Cochrane Library, CINAHL, PsycINFO, and CBM databases.

A systematic search was performed for relevant studies published before August 17, 2021. A random effects model was used to estimate the prevalence of depression and anxiety. Subgroup analysis was performed by continent or region, study setting, sex, sample size, diagnosis, and assessment method.

Twenty-two articles covering 40,956 patients were included in the meta-analysis. The pooled crude prevalence estimates of depression and anxiety were 25.2% (95% CI, 20.9%-29.6%) and 28.9% (95% CI, 16.1%-41.6%), respectively. Subgroup analyses revealed the following: (1) continent or region, study setting, sex, sample size, depression assessment method, and CRS diagnosis were significantly correlated with the prevalence of depression, and (2) continent or region, study setting, sample size, anxiety assessment method, and CRS diagnosis were significantly correlated with the prevalence of anxiety. Meta-regression analysis revealed that study setting and sample size were negatively associated with the pooled prevalence of depression. In contrast, CRS diagnosis and anxiety assessment method were positively associated with the pooled prevalence of anxiety.

Depression and anxiety are common in patients with CRS, especially among clinics. Therefore, in patients with CRS, screening and early diagnosis of depression and anxiety are necessary for prevention and treatment.

Anecdotal evidence has long suggested that patients with lower urinary tract symptoms (LUTS) develop mood disorders, such as depression and anxiety, at a higher rate than the general population and recent prospective studies have confirmed this link. Breakthroughs in our understanding of the diseases underlying LUTS have shown that many have a substantial inflammatory component and great strides have been made recently in our understanding of how this inflammation is triggered. Meanwhile, studies on mood disorders have found that many are associated with central neuroinflammation, most notably in the hippocampus. Excitingly, work on other diseases characterized by peripheral inflammation has shown that they can trigger central neuroinflammation and mood disorders. In this review, we discuss the current evidence tying LUTS to mood disorders, its possible bidirectionally, and inflammation as a common mechanism. We also review modern theories of inflammation and depression. Finally, we discuss exciting new animal studies that directly tie two bladder conditions characterized by extensive bladder inflammation (cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction) to neuroinflammation and depression. We conclude with a discussion of possible mechanisms by which peripheral inflammation is translated into central neuroinflammation with the resulting psychiatric concerns.

continuous and effective care is needed to improve the quality of life of patients with depression. The present study aimed to determine the effect of nursing home care on the quality of life of patients with Major Depressive Disorder.

This is a clinical trial study in which a total of 50 patients with Major Depressive Disorder were recruited using convenience sampling and then randomly assigned to two groups of control and intervention.

Data were collected using a demographic questionnaire and the McGill Quality of Life Questionnaire at three time-points of before, three months, and six months after the intervention. Patients in the intervention group received nursing home care in accordance with nursing process (5-6 training sessions of 1.5 to 2 h, one session every two weeks over three months). They also received telephone follow-up. Data were analyzed with SPSS software version 16.0 using independent-samples t-test, chi square and repeated measures Analysis of Variance.

The results of the present study indicated there was a significant difference in the mean score of the overall quality of life and its domains between the intervention and the control group at three and six months after the intervention.

Based on the results of the present study, it was concluded that the nursing home care program can improve the quality of life and its domains in patients with Major Depressive Disorder.

According to this study, by follow up of patients with major depression disorder after discharge and performing care and counseling interventions at home besides routine treatment plan, it is possible to prevent re-hospitalization and decrease hospitalization costs.

This study examined prescription NSAIDs as one of the leading predictors of incident depression and assessed the direction of the association among older cancer survivors with osteoarthritis.

This study used a retrospective cohort (N = 14, 992) of older adults with incident cancer (breast, prostate, colorectal cancers, or non-Hodgkin's lymphoma) and osteoarthritis. We used the longitudinal data from the linked Surveillance, Epidemiology, and End Results -Medicare data for the study period from 2006 through 2016, with a 12-month baseline and 12-month follow-up period. Cumulative NSAIDs days was assessed during the baseline period and incident depression was assessed during the follow-up period. An eXtreme Gradient Boosting (XGBoost) model was built with 10-fold repeated stratified cross-validation and hyperparameter tuning using the training dataset. The final model selected from the training data demonstrated high performance (Accuracy: 0.82, Recall: 0.75, Precision: 0.75) when applied to the test data. SHapley Additive exPlanations (SHAP) was used to interpret the output from the XGBoost model.

Over 50% of the study cohort had at least one prescption of NSAIDs. Nearly 13% of the cohort were diagnosed with incident depression, with the rates ranging between 7.4% for prostate cancer and 17.0% for colorectal cancer. The highest incident depression rate of 25% was observed at 90 and 120 cumulative NSAIDs days thresholds. Cumulative NSAIDs days was the sixth leading predictor of incident depression among older adults with OA and cancer. Age, education, care fragmentation, polypharmacy, and zip code level poverty were the top 5 predictors of incident depression.

Overall, 1 in 8 older adults with cancer and OA were diagnosed with incident depression. Cumulative NSAIDs days was the sixth leading predictor with an overall positive association with incident depression. However, the association was complex and varied by the cumulative NSAIDs days.

Inflammatory stimuli have been shown to impact brain regions involved in threat detection and emotional processing including amygdala and ventromedial prefrontal cortex (vmPFC), and to increase anxiety. Biomarkers of endogenous inflammation, including inflammatory cytokines and C-reactive protein (CRP), are reliably elevated in a subset of patients with depression and anxiety-related disorders such as post-traumatic stress disorder (PTSD), and have been associated with high anxiety in population studies. We previously reported that plasma CRP and cytokines in patients with depression were negatively correlated with resting-state functional connectivity (FC) between right amygdala and vmPFC, as assessed using both ROI to voxel-wise and targeted FC approaches, in association with symptoms of anxiety, particularly in patients with comorbid anxiety disorders or PTSD. To determine whether relationships between inflammation, right amygdala-vmPFC FC, and anxiety are reproducible across patient samples and research settings, we employed an a priori, hypothesis-driven approach to examine relationships between inflammation, targeted right amygdala-vmPFC FC and anxiety in a cohort of African American (AA) women (n = 54) recruited from an inner-city hospital population reliably found to have higher levels of inflammation (median CRP ∼ 4 mg/L) as well as symptoms of anxiety, depression and PTSD. Higher concentrations of plasma CRP were associated with lower right amygdala-vmPFC FC (r = -0.32, p = 0.017), and this relationship remained significant when controlling for age, body mass index and number of lifetime trauma events experienced, as well as severity of PTSD and depression symptoms (all p < 0.05). This amygdala-vmPFC FC was similarly associated with a composite score of three inflammatory cytokines in a subset of women where plasma was available for analysis (n = 33, r = -0.33, p = 0.058; adjusted r = -0.43, p = 0.026 when controlling for covariates including PTSD and depression symptom severity). Lower right amygdala-vmPFC FC was in turn associated with higher levels of anxiety reported to be generally experienced on the State-Trait Anxiety Inventory, trait component (adjusted r = -0.32, p = 0.039 when controlling for covariates). Exploratory analyses also revealed a negative correlation between severity of childhood maltreatment and right amygdala-vmPFC FC (r = -0.32, p = 0.018) that was independent of CRP and its association with FC, as well as an association between low amygdala-vmPFC FC and severity of PTSD symptoms, specifically the re-experiencing/intrusive symptom subscale (adjusted r = -0.32, p = 0.028 when controlling for covariates). While CRP was not linearly associated with either anxiety or PTSD symptoms, CRP concentrations were higher in women reporting clinically significant anxiety or PTSD symptom severity when these symptoms were considered together (both p < 0.05), but with no interaction. These results support our primary hypothesis that higher inflammation was associated with lower amygdala-vmPFC FC, a relationship that was detected using a hypothesis-driven, targeted approach. Findings also support that this phenotype of high CRP and low vmPFC FC was observed in association with anxiety in primary analyses, as well as symptoms of PTSD in exploratory analyses, in a cohort recruited from an inner-city population of AA women enriched for high inflammation, history of trauma exposure, and symptom severity. Larger, longitudinal samples are required to fully tease apart causal relationships between inflammatory biomarkers, FC and PTSD-related symptoms in future studies.

The origins of sex-biased differences in disease and health are of growing interest to both medical researchers and health professionals. Several major factors have been identified that affect sex differences in incidence of diseases and mental disorders. These are: sex chromosomes, sex hormones and female immunity, sexual selection and antagonistic evolution, and differential susceptibility of sexes to environmental factors. These factors work on different time scales and are not exclusive of each other. Recently, a combined Sexual Selection-Sex Hormones (SS-SH) Theory was presented as an evolutionary mechanism to explain sex-biased differences in diseases and mental disorders (Singh in J Mol Evol 89:195-213, 2021). In that paper disease prevalence trends were investigated, and non-sex-specific diseases were hypothesized to be more common in males than in females in general. They showed signs of exceptions to this trend with inflammatory diseases and stress-related mental disorders that were more common in females. We believe that the SS-SH theory requires the consideration of psycho-social stress (PSS) to explain the predominance of female-biased mental disorders and some other exceptions in their findings. Here we present a theory of sex-differential experience of PSS and provide quantitative support for the combined SS-SH-PSS Theory using age-standardized incidence rates (ASIRs) recording the levels of male- and female-bias in data obtained from different countries. The grand theory provides an evolutionary framework for explaining patterns of sex-biased trends in the prevalence of disease and health. Further exploration of women's vulnerability to social factors may help to facilitate new treatments for female-biased diseases.