Markers of inflammation and cannabis exposure are associated with an increased risk of mental disorders. In the current study, we investigated associations between cannabis use and biomarkers of inflammation.

Utilizing a sample of 914 participants from the Avon Longitudinal Study of Parents and Children, we investigated whether interleukin-6 (IL-6), tumor necrosis factor α (TNFα), C-reactive protein (CRP), and soluble urokinase plasminogen activator receptor (suPAR) measured at age 24 were associated with past year daily cannabis use, less frequent cannabis use, and no past year cannabis use. We adjusted for a number of covariates including sociodemographic measures, body mass index, childhood trauma, and tobacco smoking. We found evidence of a strong association between daily or near daily cannabis use and suPAR.

We did not find any associations between less frequent cannabis use and suPAR. We did not find evidence of an association between IL-6, TNFα or CRP, and cannabis use.

Our finding that frequent cannabis use is strongly associated with suPAR, a biomarker of systemic chronic inflammation implicated in neurodevelopmental and neurodegenerative processes is novel. These findings may provide valuable insights into biological mechanisms by which cannabis affects the brain and impacts the risk of serious mental disorders.

This study aimed to investigate changes in mRNA expression of the kynurenine pathway (KP) enzymes tryptophan 2, 3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase 1 and 2 (IDO1, IDO2), kynurenine aminotransferase 1 and 2 (KAT1, KAT2), kynurenine monooxygenase (KMO) and kynureninase (KYNU) in medicated patients with depression (n = 74) compared to age- and sex-matched healthy controls (n = 55) and in patients with depression after electroconvulsive therapy (ECT). Associations with mood score (24-item Hamilton Depression Rating Scale, HAM-D24), plasma KP metabolites and selected glucocorticoid and inflammatory immune markers known to regulate KP enzyme expression were also explored.

HAM-D24 was used to evaluate depression severity. Whole blood mRNA expression was assessed using quantitative real-time polymerase chain reaction.

KAT1, KYNU and IDO2 were significantly reduced in patient samples compared to control samples, though results did not survive statistical adjustment for covariates or multiple comparisons. ECT did not alter KP enzyme mRNA expression. Changes in IDO1 and KMO and change in HAM-D24 score post-ECT were negatively correlated in subgroups of patients with unipolar depression (IDO1 only), psychotic depression and ECT responders and remitters. Further exploratory correlative analyses revealed altered association patterns between KP enzyme expression, KP metabolites, NR3C1 and IL-6 in depressed patients pre- and post-ECT.

Further studies are warranted to determine if KP measures have sufficient sensitivity, specificity and predictive value to be integrated into stress and immune associated biomarker panels to aid patient stratification at diagnosis and in predicting treatment response to antidepressant therapy.

Suicide is the second leading cause of death in 12- to 17-year-old adolescents in the USA. Research on biological mechanisms contributing to self-harm risk that could be targeted in treatment could help to prevent suicide and self-harm episodes.

We aimed to evaluate whether markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), predict self-harm over 3 months within a sample selected for elevated suicide/self-harm risk at project entry.

Fifty-one adolescents aged 12–19 years selected for elevated suicide/self-harm risk completed three clinical interviews about suicide attempts and non-suicidal self-injury, 3 months apart. At baseline and 3 months, youth also provided blood samples, from which we assayed levels of IL-6 and CRP.

Using generalised mixed models, we found that greater levels of IL-6 predicted more self-harm episodes (odds ratio [OR] = 3.3, 95% CI: 1.1, 10.0) and specifically, non-suicidal self-injury (OR = 3.5, 95% CI: 1.1, 11.2), over 3 months.

The study findings increase our understanding of whether and how inflammation may be implicated in risk of self-harm. IL-6 may be a viable biological marker of short-term risk for self-harm.

Serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have been associated with anxiety and depression in cross-sectional and Mendelian randomisation studies, but results regarding the effect size and direction have been mixed. A recent Mendelian Randomisation (MR) study suggested that CRP may decrease and IL-6 may increase anxiety and depression symptoms.

Among 68 769 participants of the population-based Trøndelag Health Study (HUNT), we performed cross-sectional observational and one-sample MR analyses of serum CRP and two-sample MR analysis of serum IL-6. The main outcomes were symptoms of anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS) and life satisfaction assessed using a seven-level ordinal questionnaire where higher scores indicate lower life satisfaction.

In cross-sectional observational analyses, a doubling in serum CRP level was associated with 0.27% (95% CI −0.20 to 0.75) difference in HADS depression score (HADS-D), −0.77% (95% CI −1.24 to −0.29) difference in HADS anxiety score (HADS-A) and −0.10% (95% CI −0.41 to 0.21) difference in life satisfaction score. In one-sample MR analyses, a doubling in serum CRP was associated with 2.43% (95% CI −0.11 to 5.03) higher HADS-D, 1.94% (95% CI −0.58 to 4.52) higher HADS-A, and 2.00% (95% CI 0.45 to 3.59) higher life satisfaction score. For IL-6, causal point estimates were in the opposite direction, but imprecise and far from conventional criteria for statistical significance.

Our results do not support a major causal role of serum CRP on anxiety and depression symptoms and life satisfaction, but provides weak evidence that serum CRP may modestly increase anxiety and depression symptoms and reduce life satisfaction. Our findings do not support the recent suggestion that serum CRP may lower anxiety and depression symptoms.

Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers.

We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603).

Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): −0·79, 95 % CI: −1·15, −0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: −0·16, 95 % CI: −0·26, −0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: −0·20, 95 % CI: −0·31, −0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: −0·98, 95 % CI: −1·56, −0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration.

These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.

Coronavirus disease 2019 (COVID-19) infection causes a wide variety of neurological disorders by affecting both central and peripheral nervous systems. The cytokine storm (CS) has been blamed for the development of severe neurological disorders in COVID-19. However, the relationship between COVID-19 CS and neurological manifestations has not been adequately studied. Thus, we aimed to investigate the neurological presentations in patients with COVID-19 CS.

The study population consisted of hospitalized moderate-to-severe COVID-19 patients. It was divided into two groups CS (36 patients, 29.3%) and non-CS (87 patients, 70.7%) based on significant clinical symptoms, elevated inflammatory marker levels, radiological findings, and interleukin-6 levels (IL-6).

The three most common neurological symptoms in the CS group were altered level of consciousness, headache, and unsteadiness. Altered level of consciousness was higher in the CS group (69.4%) than the non-CS group (25.3%) (p:0.001). The frequency of headache was comparable in both groups (p:0.186). The number of patients requiring intensive care unit and intubation was higher in the CS group (p:0.005 and p:0.001). The mortality rate in the CS group (38.9%) was higher than the non-CS group (8.0%) (p:0.001). IL-6, CRP, ferritin, neutrophil-lymphocyte ratio, procalcitonin, and D-dimer levels were higher in the CS group (for all p:0.001) while lymphocyte count was lower (p:0.003).

The most common neurological presentation in patients with CS was altered level of consciousness. The presence of CS was an independent risk factor for high mortality.

Unipolar mania is not included in the diagnostic and statistical manual of mental disorders-5 (DSM-5) as a separate diagnosis, although it is defined by widely accepted diagnostic criteria. The aim of this study was to investigate the differences between unipolar mania and bipolar disorder in terms of clinical and inflammatory parameters.

The data of 495 hospitalised patients with bipolar disorder diagnoses were analysed retrospectively. Forty met the diagnostic criteria for unipolar mania. Two patients refused to participate in the study. Thirty-eight unipolar mania patients and 42 randomly selected patients with bipolar disorder diagnosis were included in the study. The two groups were compared in terms of sociodemographic, clinical characteristics, serum brain-derived neurotrophic factor, C-reactive protein (CRP), leucocyte and cytokine levels.

A total of 40 (8.08%) of 495 patients diagnosed with bipolar disorder met the unipolar mania diagnostic criteria. The number of manic episodes and the number of hospitalisations were statistically higher in the unipolar mania group than in the bipolar disorder group. Among all the manic symptoms, the incidence of symptoms such as euphoria, increased sexual interest, grandiosity and delusions were found to be statistically higher in the unipolar mania group. Interleukin (IL)-6 and CRP levels were significantly higher in the unipolar mania group than in the bipolar disorder group.

Unipolar mania differs from bipolar disorder in terms of clinical features and serum IL-6 and CRP levels.

To investigate if toll-like receptor (TLR) 4/nuclear factor-kappa B (NF-κB) signaling pathways mediated crush injury induced acute kidney injury (AKI) in rats, and if TAK-242 (a specific inhibitor of TLR4) attenuates the injury through inhibiting the signaling pathways.

This study was divided into two parts: (1) Establish the crush injury model: 50 rats were randomly divided into control group and four crush injury groups (n = 10/group). Crush injury groups were given 3kg pressure for eight hours and were sacrificed at the time points of 0h, 6h, 12h, and 24h after relieving pressure. And (2) Select the most obvious injury group (12h group) for drug intervention group. Thirty rats were randomly divided into control group, 12h group, and 12h+TAK-242 group (n = 10/group). Two parts detection were as follows: pathological changes of kidney tissues were observed in Haematoxylin and Eosin (HE) staining. Serum creatinine, blood urea nitrogen (BUN), myoglobin (Mb), and blood potassium were examined by automatic biochemical analysis instrument. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The TLR4 messenger ribonucleic acid (mRNA), TLR4, and P65 were detected by real-time polymerase chain reaction (PCR), western blot, immunohistochemistry staining.

Compared with the control group, kidney tissues were damaged in crush injury groups, and most obvious in the 12h group. The level of serum creatinine, BUN, Mb, blood potassium, IL-6, TNF-α, and TLR4mRNA were increased in the crush injury groups and significantly increased in the 12h group (P <.05). The TLR4 and P65 were significantly increased in the 12h group (P <.05). Compared with the 12h group, kidney tissue damage was significantly reduced in the TAK-242 group (P <.05). The level of serum creatinine, BUN, Mb, blood potassium, IL-6, TNF-α, TLR4mRNA, TLR4, and P65 in the TAK-242 group were significantly reduced (P <.05).

The present findings conclude that TLR4/NF-κB signaling pathways mediated crush injury induced AKI in rats, and TAK-242 attenuates the injury through inhibiting the signaling pathways.

There is substantial evidence that many depressed individuals experience impaired executive functioning. Understanding the causes of executive dysfunction in depression is clinically important because cognitive impairment is a substantial contributor to functional impairment. This study investigated whether elevated levels of an inflammatory cytokine [interleukin-6 (IL-6)] and/or higher body mass index (BMI) concurrently and/or prospectively accounted for the relationship between depressive symptoms and impaired executive functioning in adolescents.

A diverse, community sample of adolescents (N = 288; mean age = 16.33; 51.4% female; 59.0% African-American) completed assessments of height and weight, IL-6, depressive symptoms, and self-report/behavioral measures of executive functioning (selective attention, switching attention) and future orientation annually over 3 years. Adolescents experiencing acute illness or medical conditions that affect inflammation were excluded from analyses. Path analysis within a structural equation modeling framework simultaneously examined the concurrent and prospective relationships between BMI, IL-6, depressive symptoms, and the measures of cognitive functioning across three timepoints.

Across all timepoints, higher BMI was prospectively associated with higher levels of IL-6 and depressive symptoms, while higher levels of IL-6 were associated with worse performance on three behavioral and self-report measures of cognitive functioning. Higher depressive symptoms also were prospectively associated with elevated IL-6 and both higher depressive symptoms and a higher BMI predicted worse future executive functioning via increased IL-6.

More severe depressive symptoms and increased BMI may disrupt executive functioning via elevated IL-6.

The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.

The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.

Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.

There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025).

Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.

Acute kidney injury is a frequent complication after cardiac surgery with cardiopulmonary bypass in infants. Neutrophil gelatinase-associated lipocalin has been suggested to be a promising early biomarker of impending acute kidney injury. On the other hand, neutrophil gelatinase-associated lipocalin has been shown to be elevated in systemic inflammatory diseases without renal impairment. In this secondary analysis of data from our previous study on acute kidney injury after infant cardiac surgery, our hypothesis was that neutrophil gelatinase-associated lipocalin may be associated with surgery-related inflammation.

We prospectively enrolled 59 neonates and infants undergoing cardiopulmonary bypass surgery for CHD and measured neutrophil gelatinase-associated lipocalin in plasma and urine and interleukin-6 in the plasma. Values were correlated with postoperative acute kidney injury according to the paediatric Renal-Injury-Failure-Loss-Endstage classification.

Overall, 48% (28/59) of patients developed acute kidney injury. Of these, 50% (14/28) were classified as injury and 11% (3/28) received renal replacement therapy. Both plasma and urinary neutrophil gelatinase-associated lipocalin values were not correlated with acute kidney injury occurrence. Plasma neutrophil gelatinase-associated lipocalin showed a strong correlation with interleukin-6. Urinary neutrophil gelatinase-associated lipocalin values correlated with cardiopulmonary bypass time.

Our results suggest that plasma and urinary neutrophil gelatinase-associated lipocalin values are not reliable indicators of impending acute kidney injury in neonates and infants after cardiac surgery with cardiopulmonary bypass. Inflammation may have a major impact on plasma neutrophil gelatinase-associated lipocalin values in infant cardiac surgery. Urinary neutrophil gelatinase-associated lipocalin may add little prognostic value over cardiopulmonary bypass time.