Schizophrenia (SCZ) shows marked biological heterogeneity, with negative symptoms linked to poor outcomes and hypothesized immune dysregulation. This study examined whether a peripheral cytokine–long non-coding RNA (lncRNA) panel could distinguish patients with SCZ and Brief Negative Symptom Scale (BNSS)-defined subgroups from healthy controls (HC).

Forty-one hospitalized patients with SCZ completed the BNSS and the Positive and Negative Syndrome Scale (PANSS). Twenty HCs, frequency-matched for age and sex, served as comparison samples. Severe negative-symptom subgroups were defined using two BNSS criteria: a broader (SNS1) and a more restrictive (SNS2) threshold. Serum cytokines—interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10)—and leukocyte lncRNAs (MALAT1, NEAT1, MEG3) were quantified by enzyme-linked immunosorbent assay and quantitative RT-PCR. Covariate-adjusted logistic and multinomial models (adjusting for age, sex, body mass index, and smoking) assessed discrimination using area under the receiver-operating-characteristic curve (AUC) and interquartile-range odds ratios (OR_IQR).

IL-6 correlated with PANSS Total (ρ = .48, p = .001) and Negative (ρ = .34, p = .032) scores and was higher in SCZ than HC (p = .033), with further increases in SNS subgroups. NEAT1 was significantly reduced only within BNSS-defined subgroups (p ≤ .025). The dual-marker pattern (IL-6 ↑, NEAT1 ↓) showed the strongest discrimination for SNS1 versus HC (AUC = 0.85) and the steepest multinomial contrasts for SNS2 (IL-6 OR_IQR = 4.98; NEAT1 OR_IQR = 0.11).

Elevated IL-6 and decreased NEAT1 define a peripheral signature linked to negative-symptom severity in SCZ and may support biologically informed stratification and longitudinal research.

Emerging evidence suggests that metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) may increase vulnerability to neurodegenerative disorders. However, the link between PCOS and Alzheimer’s disease (AD)-related pathology remains unclear.

In this cross-sectional study, plasma levels of β-amyloid (Aβ40, Aβ42), phosphorylated tau (p-tau181), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified in women with PCOS and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, TNF-α) and hormonal parameters were assessed. Mediation and moderation analyses were conducted to explore metabolic and hormonal pathways underlying biomarker alterations.

Among 400 women (200 PCOS, 200 controls), age and BMI were comparable (P > 0.05). Compared with controls, PCOS participants had increased Aβ40, p-tau181, NfL and GFAP, a slightly higher Aβ42, and a lower Aβ42/40 ratio (all P < 0.05). p-tau181 correlated positively with HOMA-IR (r = 0.41) and IL-6 (r = 0.36), while Aβ42/40 ratio correlated negatively with HOMA-IR (r = –0.27). In multivariable analysis, p-tau181 (aOR = 1.34, 95% CI 1.05–1.71), IL-6 (aOR = 1.19) and TNF-α (aOR = 1.14) were independent predictors of insulin resistance. Mediation analysis indicated that HOMA-IR, IL-6 and TNF-α jointly mediated ∼ 71% of the PCOS–p-tau181 association, suggesting a metabolic–inflammatory pathway linking PCOS to AD-related tau pathology.

PCOS is linked to peripheral markers of early Alzheimer’s pathology, largely mediated by insulin resistance and inflammation. PCOS may provide a clinical context to explore metabolic–inflammatory contributors to early neurodegenerative changes.

Major depression (MDD) is linked to neuro-immune, metabolic, and oxidative stress (NIMETOX) pathways. The gut microbiome may contribute to these pathways via leaky gut and immune-metabolic processes.

To identify gut microbial alterations in MDD and to quantify functional pathways and enzyme gene families and integrate these with the clinical phenome and immune–metabolic biomarkers of MDD.

Shotgun metagenomics with taxonomic profiling was performed in MDD versus controls using MetaPhlAn v4.0.6, and functional profiling was conducted using HUMAnN v3.9, aligning microbial reads to species-specific pangenomes (Bowtie2 v2.5.4) followed by alignment to the UniRef90 v201901 protein database (DIAMOND v2.1.9).

Gut microbiome diversity, both species richness and evenness, is quite similar between MDD and controls. The top enriched taxa in the multivariate discriminant profile of MDD reflect gut dysbiosis associated with leaky gut and NIMETOX mechanisms, i.e., Ruminococcus gnavus, Veillonella rogosaem and Anaerobutyricum hallii. The top four protective taxa enriched in controls indicate an anti-inflammatory ecosystem and microbiome resilience, i.e., Vescimonas coprocola, Coprococcus, Faecalibacterium prausnitzii, and Faecalibacterium parasitized. Pathway analysis indicates loss of barrier protection, antioxidants and short-chain fatty acids, and activation of NIMETOX pathways. The differential abundance of gene families suggests that there are metabolic distinctions between both groups, indicating aberrations in purine, sugar, and protein metabolism. The gene and pathway scores explain a larger part of the variance in suicidal ideation, recurrence of illness, neurocognitive impairments, immune functions, and atherogenicity.

The gut microbiome changes might contribute to activated peripheral NIMETOX pathways in MDD.

As the global shift towards autocracy continues and soft political repression rises, it is crucial to understand its long-term health implications. Typical tactics of soft political repression are surveillance, denunciation and harassment, operating beneath the threshold of criminal or violent persecution. Despite its prevalence, soft repression remains underexplored, particularly in terms of its psychobiological health consequences.

The current study investigates the long-term sequelae of soft political repression in the German Democratic Republic (GDR: 1949–1990), focusing on psychological distress, systemic inflammation and cellular ageing.

The cross-sectional laboratory study included 100 50–78 years old participants from the states of Thuringia and Saxony in Germany. Participants in the repression group (n = 49) had experienced at least two forms of state-organised soft repression in the GDR. The age, gender and origin matched control group reported no such experiences. Psychological measures included depressive, anxiety and trauma symptoms. Physiological health outcomes were measured through the inflammatory markers interleukin-6 and high sensitivity C-reactive protein (hs-CRP), as well as telomere length as a marker of cellular ageing. Resilience, social support and socioeconomic status were included in the analyses as potential buffers of repression effects.

Participants with repression experience (versus control group) scored significantly higher on all psychological distress variables. Furthermore, they exhibited higher levels of interleukin-6, indicating increased systemic inflammation. No group differences were found for hs-CRP or telomere length. However, in the repression group, lower social support was associated with shorter telomeres.

This study is the first to explore the psychobiological health consequences of soft political repression. Findings emphasise its long-term consequences on the psyche and immune system and highlight the potential role of social support in mitigating cellular ageing. As authoritarian tactics are becoming more prevalent worldwide, understanding the impact of soft repression on health is essential for supporting affected individuals.

Contrary to the negative acute-phase protein (APP) response, there is no consistent correlation between serum pentameric C-reactive protein (pCRP) and major depression (MDD). Monomeric CRP (mCRP), a dissociation product of pCRP under immune-inflammatory conditions, exhibits pro-inflammatory effects; however, it has not been investigated in MDD or its subtypes, major dysmood disorder (MDMD) and simple dysmood disorder (SDMD).

To examine serum mCRP, albumin, transferrin, M1 macrophage and Thelper-17 immune profiles, and adverse childhood experiences (ACEs) in MDD, MDMD and SDMD.

Seventy-nine MDMD patients, 30 SDMD patients, and 40 controls were included. Serum mCRP was measured by ELISA; albumin, transferrin, and pCRP by biochemical assays; and cytokines using Luminex technology.

MDMD patients showed significantly higher mCRP compared with SDMD and controls, while both patient groups exhibited reduced albumin and transferrin. Combining mCRP with albumin and transferrin showed an adequate accuracy for MDD (area under the ROC Curve = 0.793). Adding IL-17A and ACEs improved accuracy (ROC = 0.855). Serum mCRP levels are additionally associated with pCRP, M1 macrophage profile, body mass index, and ACEs. Up to 36.6% of the variance in overall severity of depression was explained by mCRP, T-helper-17 profile, ACEs (all positively), albumin and transferrin (both inversely).

Future research in MDD should employ mCRP rather than pCRP as a biomarker of depression/MDMD. Combining mCRP with biomarkers of the negative acute-phase response identified 63.7% of MDD patients with a smouldering acute-phase response, with a specificity of 82.1%. We recommend to assess mCRP rather than pCRP in MDD studies.

Five-Factor Model (FFM) personality traits are associated with cognitive function, however, biological pathways accounting for these relations are not well understood. Here, we examined associations between individual FFM traits (self- and informant-reported) and cognitive function (episodic memory, executive control, and working memory), and the indirect effect of a latent index of cardiometabolic risk (composed of adiposity, glycemic control, blood pressure, blood lipids, and inflammation) in a midlife sample.

Participants included 856 volunteers (M = 44.6 ± 6.9 years, range: 30 – 54; Female 54%; Caucasian 85%) from the Adult Health and Behavior (AHAB) registry. Structural equation models were used to: (1) regress cognitive performance on FFM traits and (2) test indirect effects of cardiometabolic risk. Age, sex, and race were included as covariates in all models.

Lower Neuroticism, higher Openness, and higher Agreeableness were significantly associated with better performance in each cognitive domain, and higher Conscientiousness was associated with better working memory. Associations between these traits and executive control were accounted for by a significant indirect effect of lower cardiometabolic risk, and in component-specific analyses, by indirect effects of adiposity and systemic inflammation.

Overall, FFM personality traits were associated with multiple domains of cognitive performance, which, in the case of executive control, was partially explained by differences in cardiometabolic risk. Future investigations should examine whether these pathways account for longitudinal change in cognition.

Respiratory diseases are increasing global health burden with persistently high morbidity and mortality. Extracellular vesicles (EVs), which are virtually released by all cell types and carry a variety of molecules like miRNAs, have emerged as crucial mediators of intercellular communication. They play a key role in maintaining lung homeostasis and are involved in the pathogenesis of various respiratory conditions. Furthermore, mesenchymal stromal cell-derived EVs (MSC-EVs) have shown significant therapeutic potential due to their anti-inflammatory, antimicrobial, and reparative properties.

This narrative review critically assesses the current body of literature on the roles of EVs in respiratory diseases. We examine evidence from pre-clinical and clinical studies that investigate EVs as biomarkers and therapeutics for conditions including asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), lung cancer, and pulmonary arterial hypertension (PAH).

EVs reflect the physiological or pathological state of their parental cells, making them promising multimodal biomarkers for the early diagnosis and monitoring of disease progression. Additionally, MSC-EVs function as effective, cell-free therapeutic agents. In a variety of disease models, they demonstrate efficacy by modulating immune responses, enhancing alveolar fluid clearance, and restoring epithelial and endothelial barrier integrity, leading to improved survival and outcomes.

EVs hold a dual and transformative potential in respiratory medicine. They may serve as valuable diagnostic and prognostic tools, and their application as cell-free therapeutics represents a novel and promising strategy for treating a wide spectrum of debilitating respiratory diseases.

Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism.

To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression.

Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism.

Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.

There are differences in IgA responses to tryptophan catabolites (TRYCATs) in major neurocognitive psychosis (MNP) versus simple neurocognitive psychosis (SNP) and normal controls. MNP and SNP are distinct schizophrenia classes which are differentiated by neurocognitive deficits, phenome features, and biomarker pathways. Nevertheless, there is no data on serum concentrations of those TRYCATs in MNP and SNP. The aim of the present study is to examine serum concentrations of tryptophan and TRYCATs in MNP versus SNP and controls.

This case-control study examines serum levels of tryptophan and TRYCATs in 52 MNP patients, 68 SNP patients and 60 controls in association with overall severity of schizophrenia (OSOS).

MNP patients show lower tryptophan, kynurenic acid (KA), 3-OH-anthranilic acid (3HAA), and higher anthranilic acid (AA) and quinolinic acid (QA) than SNP patients and controls. There were no differences between SNP and controls in these TRYCATs. Kynurenine (KYN) was lower in MNP+SNP than in controls. We found that 36.5% of the variance in OSOS was explained by the combined effects of lowered tryptophan, KA, and 3-HK, and increased QA and AA. The most important biomarkers of MNP and OSOS were the QA/KA ratio followed by the QA/3HAA ratio.

The alterations in serum TRYCAT levels further emphasize that MNP and SNP represent two biologically distinct subtypes of schizophrenia. The reductions in TRYCATs diminish the antioxidant and immunoregulatory functions of the TRYCAT pathway. Elevated QA levels may exacerbate the disruption of the blood-brain barrier and the immune-related and oxidative neurotoxicity in MNP.

Metabolic syndrome (MetS) is highly prevalent among adults and is frequently accompanied by depressive symptoms. While high-sensitivity C-reactive protein (hsCRP) has been proposed as a potential indicator of depression, existing evidence remains inconclusive.

This study aimed to determine whether increased serum hsCRP or other immune-metabolic biomarkers are associated with depressive symptoms in drug-naïve individuals with obesity and MetS.

A total of 88 drug-naïve patients with obesity and MetS but without coronary-artery disease were enrolled and serum levels of neuro-immune and metabolic biomarkers were assessed.

In MetS, the severity of depression, as assessed using the von Zerssen Depression Rating (VZDR) scale was significantly associated with interleukin (IL)-6, leukocyte numbers, triglyceride x glucose (Tyg) index, low-density lipoprotein cholesterol, Apolipoprotein B (all positively) and mean platelet volume (MPV), visfatin and adiponectin (all negatively). There were no significant associations between hsCRP and severity of depression. In MetS patients, hsCRP is strongly associated with increased leukocyte numbers, alkaline phosphatase, γ-glutamyl transferase, uric acid, platelet numbers and MPV, thereby shaping a distinct subtype of MetS, which is not related to depression.

Our findings indicate that depressive symptoms in MetS patients are associated with immune–metabolic biomarkers indicating immune activation, atherogenicity and insulin resistance, but not with hsCRP. The reason is that hsCRP in MetS is a biomarker of a specific MetS subtype that is characterized by megakaryopoiesis, hepatocyte activation, and uric acid production, which were not associated with depression.

Longitudinal studies have revealed that raised levels of inflammatory markers and trauma in childhood are associated with psychopathology in adulthood.

To examine whether inflammation in childhood mediates the effects of genetic risk and trauma on psychopathology in early adulthood.

Measures of trauma exposure, inflammation and psychopathology were collected from the Avon Longitudinal Study of Parents and Children. Exposure to trauma was measured from 5 to 11 years of age; C-reactive protein and interleukin-6 levels were measured at 9 years; and depression, anxiety disorders, negative symptoms and psychotic experiences were assessed at 24 years. Polygenic risk scores (PRSs) were created for schizophrenia, depression, anxiety and psychotic experiences. Mediation analyses were conducted using imputed data (N: 7859 to 8700) to investigate whether inflammation mediated the associations of genetic risk and childhood trauma with psychopathology.

Most psychiatric PRSs were associated with multiple psychopathological outcomes in adulthood, with the exception of the PRS for psychotic experiences. Childhood trauma was associated with all psychopathology. However, there was no strong evidence that inflammatory markers in childhood mediated associations among PRSs, trauma and psychopathology. Sensitivity analyses using outcomes from age 18 and PRSs based on single-nucleotide polymorphisms that met more stringent standards of evidence of association gave results consistent with those of our primary analyses.

We found little evidence that interleukin-6 or C-reactive protein mediated the pathway between genetic liability for psychiatric phenotypes or trauma and subsequent psychopathology. Longitudinal investigation of other inflammatory and non-inflammatory pathways is required to identify modifiable targets and inform novel treatment strategies for individuals at genetic or trauma-related risk of psychiatric illness.