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.

In this short narrative review, we would like to discuss the immunomodulatory effects of South African geranium (Pelargonium sidoides) root extract EPs7630 in treating acute rhinosinusitis. The plant has been used for centuries to treat respiratory tract inflammation, such as sinusitis, pharyngitis and bronchitis. South African geranium is rich in polyphenols, flavonoids, tannins, diterpenes and proanthocyanidins, but the main constituent is a type of coumarin called ‘umckalin’ (6–hydroxy–5,5–dimethoxy–coumarin). The substance is standardised as an aqueous-ethanolic extract from the root of this plant under the code name EPs7630.

The article presents the results of in vitro and in vivo studies of administering this herbal drug in acute viral, post-viral and bacterial rhinosinusitis. The focus is on the immunomodulatory effects of EPs7630 during the therapy of this acute inflammation of the nasal mucosa.

According to the results of some studies, EPs7630 stimulates monocyte-dependent activity and inhibits neutrophil-dependent chemokine activity. However, given the small number of studies, the level of evidence is low, implying the need for new research.

Particular attention should be paid to the effect of EPs7630 on bradykinin, the mediator that triggers most inflammatory processes in acute rhinosinusitis.

Immune dysregulation contributes to the pathophysiology of depression and is a potential link between depression and comorbid medical conditions. DNA methylation is a dynamic transcriptional regulator of the immune system.

To study changes in DNA methylation of disease- and comorbidity-associated immune genes in patients with and without depression diagnoses from the German BiDirect Study.

We performed a cross-sectional (baseline, y0) and longitudinal (consecutive assessments at 3-year intervals, y0, y3, y6) differential methylation analyses of 382 immune-related genes associated with depression, obesity, diabetes and/or gout in 276 patients with depression and in 207 individuals without a lifetime depression diagnosis from the BiDirect Study. In addition, we applied unsupervised clustering to identify subgroups of individuals with depression based on longitudinal methylation patterns.

There were no significant methylation changes between individuals with depression and controls at baseline. Follow-up analyses used to assess the top (P < 0.05) 151 methylation probes longitudinally identified 42 CpG sites that showed time-dependent changes associated with depression, and defined 3 depression clusters with differential profiles of serum inflammation markers at baseline. The implicated genes corresponded in the majority to those associated with diabetes risk, and were enriched in processes relevant for haematopoiesis.

Our results suggest that immune dysregulation associated with DNA methylation profiles contributes to the pathophysiology of depression and is a plausible link to chronic medical conditions such as diabetes.

This study aims to ascertain the effect of baseline IL-1Ra and IL-8 in the treatment response of patients with major depressive disorder (MDD) and to clarify the relationship between inflammation markers and depression.

We recruited 242 patients with a Beck Depression Inventory (BDI) score ≥ 17 referred to secondary care in Finland. The patients’ serum IL-1Ra and IL-8 concentrations were measured at baseline. Montgomery-Åsberg Depression Rating Scale (MADRS) tests and Alcohol Use Disorders Identification Tests (AUDIT) were administered at baseline and six weeks. The Antidepressant treatments varied: somewere started, others changed or continued their previous medication, and others had their doses adjusted. Patients started behavioral activation therapy. Linear regression was used with a relative MADRS score change during six weeks as the dependent variable and patient age, AUDIT score, BMI, daily number of cigarettes smoked, sex, and serum IL-1Ra and IL-8 concentrations as independent variables.

Higher baseline serum IL-1Ra and IL-8 levels were associated with a smaller relative change in the MADRS-score within the first six weeks of treatment in linear regression analysis (p<0.001 and p=0.007, respectively). In further analysis comparing groups with ≤ 24 and > 24 MADRS score only the ≤ 24 MADRS score group showed a similar association.

Higher baseline IL-1Ra and IL-8 concentrations were associated with a lesser relative response to depression treatment, particularly in patients with mild depression. Results on IL-8 concur with earlier findings whereas the association between higher IL-1Ra serum concentrations reduced treatment response is a novel finding.

The neurobiological basis of suicidal behaviour remains poorly understood. However, emerging evidence suggests that inflammation and vascular homeostasis factors may play a role in its pathophysiology. Childhood trauma, through immune system dysfunction and increased risk of suicidal behaviours, might influence these associations. This study examined the relationships between immune-inflammatory and vascular homeostasis-related markers and their interaction with childhood trauma in relation to a history of suicide attempts in individuals with depression.

A total of 328 patients with major depression were recruited: 166 with a history of suicide attempts and 162 without. Using multivariate binary logistic regression models adjusted for cofounders, we examined the associations between childhood trauma, levels of platelet-related immune markers (serotonin, MCP-1, TSP-1, TSP-2, PDGF-AB, PDGF-BB), and suicide attempt history. Independent associations between PDGF-BB, childhood trauma, and suicide attempts were further assessed using interaction models. Stratified sensitivity analyses based on childhood trauma history were also conducted.

Childhood trauma consistently emerged as associated with suicide attempts across all models. Among the measured biomarkers, higher TSP-2 levels were associated with a suicide attempt history, independent of childhood trauma. Meanwhile, while PDGF-BB alone was not directly linked to suicide attempt history, the interaction analysis revealed that individuals with lower PDGF-BB levels and more severe childhood trauma were more likely to have attempted suicide.

TSP-2 and PDGF-BB are potential biomarkers linked to suicide attempts, with distinct roles in the interplay between biological processes and early-life adversity. These insights can inform the biomarker-informed development of tailored prevention and treatment strategies.

C-reactive protein (CRP) level in blood is a standard marker for systemic inflammation. Inflammation is central in chronic subdural hematoma (CSDH) pathophysiology, and inflammatory biomarkers may hold clinical potential in assessing the level of inflammation induced by a CSDH. This study explores the role of CRP in patients with CSDH by (1) measuring systemic and subdural CRP levels, (2) investigating CRP as a potential predictor for recurrent CSDH and (3) comparing CRP levels between the first and second operations in patients with CSDH recurrence.

CRP levels were measured both in systemic blood and subdural fluid from adult CSDH patients. Recurrence rate and mortality within 90 days were recorded. In total, 111 patients were included, of whom 25 were operated on for CSDH recurrence.

Systemic CRP levels (2.54 mg/L (1.40–9.75)) were higher than subdural levels (2.09 mg/L [0.99–5.22]) (p < 0.0001) but within the clinically defined normal CRP range of < 3 mg/L. Neither systemic nor subdural CRP levels could predict recurrence. Both systemic and subdural CRP levels in recurrent CSDH patients were higher at the time of the second surgery compared to the first surgery (psystemic = 0.004 and psubdural < 0.0001).

This is the first study to establish a correlation between systemic and subdural CRP levels in CSDH patients. The increased levels of CRP at the time of the second surgery may demonstrate a constantly evolving inflammatory process toward the development of a recurrence.

Sleep disturbances are prevalent in major depressive disorder (MDD). Emerging evidence suggests a bidirectional relationship between inflammation and sleep disturbances, but the role of peripheral inflammatory markers in subjective sleep quality in treatment-resistant depression (TRD) remains unclear.

34 MDD patients (20 TRD and 14 non-TRD) and 34 healthy controls were enrolled. Participants underwent clinical assessments, including the Hamilton Rating Scale for Depression and Pittsburgh Sleep Quality Index (PSQI). Serum levels of inflammatory markers, including soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein, were measured. General linear models were used to assess associations between inflammatory markers and subjective sleep quality, adjusting for relevant covariates.

Patients with MDD scored higher in PSQI than healthy subjects. Higher serum levels of sTNF-αR1 were associated with longer sleep latency across the TRD and non-TRD groups. Elevated serum sIL-2R levels correlated with poorer overall sleep quality among patients with MDD.

These findings underscored the importance of considering inflammatory pathways in understanding sleep disturbances in depression. Longitudinal studies are needed to elucidate causal relationships and inform potential therapeutic interventions targeting both inflammation and sleep in MDD.

Neuropsychiatric disorders in preeclampsia (PE) women are prevalent and worsen PE outcome. Immune-related biomarkers including soluble sCD80 and cytotoxic T-lymphocyte antigen-4 (sCTLA-4) are not well studied in relation to depression, anxiety, and chronic fatigue due to PE.

The aim is to study serum immune-inflammatory biomarkers of PE and delineate their associations with the Hamilton Depression (HAMD), Anxiety (HAMA), and Fibro-Fatigue (FF) rating Scale scores. sCD80, sCTLA-4, vitamin D, granulocyte-macrophage colony-stimulating factor, zinc, copper, magnesium, and calcium were measured in 90 PE compared with 60 non-PE pregnant women.

PE women show higher depression, anxiety and FF rating scale scores as compared with control women. sCTLA-4, sCD80, and copper were significantly higher and zinc, magnesium, and calcium significantly lower in PE women than in controls. Multiple regression analysis showed that around 55.8%-58.0% of the variance in the HAMD, HAMA and FF scores was explained by the regression on biomarkers; the top 3 most important biomarkers were sCTLA-4, sCD80, and vitamin D. The sCTLA-4/sCD80 ratio was significantly and inversely associated with the HAMD/HAMA/FF scores. We found that around 70% of the variance in systolic blood pressure could be explained by sCTLA-4, vitamin D, calcium, and copper.

The findings underscore that PE and depression, anxiety, and chronic fatigue symptoms due to PE are accompanied by activation of the immune-inflammatory response system. More specifically, disbalances among soluble checkpoint molecules seem to be involved in the pathophysiology of hypertension and neuropsychiatric symptoms due to PE.