Peripheral Inflammatory Markers Research Articles

Interpretable Estimation of Suicide Risk and Severity from Complete Blood Count Parameters with Explainable Artificial Intelligence Methods.

The peripheral inflammatory markers are important in the pathophysiology of suicidal behavior. However, methods for practical uses haven't been developed enough yet. This study developed predictive models based on explainable artificial intelligence (xAI) that use the relationship between complete blood count (CBC) values and suicide risk and severity of suicide attempt. 544 patients who attempted an incomplete suicide between 2010-2020 and 458 healthy individuals were selected. The data were obtained from the electronic registration systems. To develop prediction models using CBC values, the data were grouped in two different ways as suicidal/healthy and attempted/non-attempted violent suicide. The data sets were balanced for the reliability of the results of the machine learning (ML) models. Then, the data was divided into two; 80% of as the training set and 20% as the test set. For suicide prediction, models were created with Random Forest, Logistic Regression, Support vector machines and XGBoost algorithms. SHAP, was used to explain the optimal model. Of the four ML methods applied to CBC data, the best-performing model for predicting both suicide risk and suicide severity was the XGBoost model. This model predicted suicidal behavior with an accuracy of 0.83 (0.78-0.88) and the severity of suicide attempt with an accuracy of 0.943 (0.91-0.976). Lower levels of NEU, WBC, MO, NLR, MLR and, age higher levels of HCT, PLR, PLT, HGB, RBC, EO, MPV and, BA contributed positively to the predictive created model for suicide risk, while lower PLT, BA, PLR and RBC levels and higher MO, EO, HCT, LY, MLR, NEU, NLR, WBC, HGB and, age levels have a positive contribution to the predictive created model for violent suicide attempt. Our study suggests that the xAI model developed using CBC values may be useful in detecting the risk and severity of suicide in the clinic.

The association between inflammatory markers in blood and cerebrospinal fluid: a systematic review and meta-analysis.

Neuroinflammatory processes have been hypothesized to play a role in the pathogenesis of psychiatric and neurological diseases. Studies on this topic often rely on analysis of inflammatory biomarkers in peripheral blood. Unfortunately, the extent to which these peripheral markers reflect inflammatory processes in the central nervous system (CNS) is unclear. We performed a systematic review and found 29 studies examining the association between inflammatory marker levels in blood and cerebrospinal (CSF) samples. We performed a random effects meta-analysis of 21 studies (pooled n = 1679 paired samples) that reported the correlation of inflammatory markers in paired blood-CSF samples. A qualitative review revealed moderate to high quality of included studies with the majority of studies reporting no significant correlation of inflammatory markers between paired blood-CSF. Meta-analyses revealed a significant low pooled correlation between peripheral and CSF biomarkers (r = 0.21). Meta-analyses of individual cytokines revealed a significant pooled correlation for IL-6 (r = 0.26) and TNFα (r = 0.3) after excluding outlier studies, but not for other cytokines. Sensitivity analyses showed that correlations were highest among participants with a median age above 50 (r = 0.46) and among autoimmune disorder patients (r = 0.35). This systematic review and meta-analysis revealed poor correlation between peripheral and central inflammatory markers in paired blood-CSF samples, with increased correlations in certain study populations. Based on the current findings, peripheral inflammatory markers are a poor reflection of the neuroinflammatory profile.

Improving the models for prognosis of aneurysmal subarachnoid hemorrhage with the neutrophil-to-albumin ratio.

Many peripheral inflammatory markers were reported to be associated with the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to identify the most promising inflammatory factor that can improve existing predictive models. The study was based on data from a 10 year retrospective cohort study at Sichuan University West China Hospital. We selected the well-known SAFIRE and Subarachnoid Hemorrhage International Trialists' (SAHIT) models as the basic models. We compared the performance of the models after including the inflammatory markers and that of the original models. The developed models were internally and temporally validated. A total of 3,173 patients were included in this study, divided into the derivation cohort (n = 2,525) and the validation cohort (n = 648). Most inflammatory markers could improve the SAH model for mortality prediction in patients with aSAH, and the neutrophil-to-albumin ratio (NAR) performed best among all the included inflammatory markers. By incorporating NAR, the modified SAFIRE and SAHIT models improved the area under the receiver operator characteristics curve (SAFIRE+NAR vs. SAFIRE: 0.794 vs. 0.778, p = 0.012; SAHIT+NAR vs. SAHIT: 0.831 vs. 0.819, p = 0.016) and categorical net reclassification improvement (SAFIRE+NAR: 0.0727, p = 0.002; SAHIT+NAR: 0.0810, p < 0.001). This study illustrated that among the inflammatory markers associated with aSAH prognosis, NAR could improve the SAFIRE and SAHIT models for 3 month mortality of aSAH.

Peripheral inflammation in behavioural variant frontotemporal dementia: associations with central degeneration and clinical measures

BackgroundNeuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters.MethodsThirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Group differences were tested using Student’s t test, Mann‒Whitney U test, or ANOVA. Partial correlation analysis and multivariable regression analysis were implemented using age and sex as covariates to explore the association between peripheral inflammatory markers, neuroimaging, and clinical measures. The false discovery rate was used to correct for the multiple correlation test.ResultsPlasma levels of six factors, including interleukin (IL)-2, IL-12p70, IL-17A, tumour necrosis superfamily member 13B (TNFSF/BAFF), TNFSF12 (TWEAK), and TNFRSF8 (sCD30), were increased in the bvFTD group. Five factors were significantly associated with central degeneration, including IL-2, IL-12p70, IL-17A, sCD30/TNFRSF8, and tumour necrosis factor (TNF)-α; the association between inflammation and brain atrophy was mainly distributed in frontal–limbic–striatal brain regions, whereas the association with brain metabolism was mainly in the frontal–temporal–limbic–striatal regions. BAFF/TNFSF13B, IL-4, IL-6, IL-17A and TNF-α were found to correlate with clinical measures.ConclusionPeripheral inflammation disturbance in patients with bvFTD participates in disease-specific pathophysiological mechanisms, which could be a promising target for diagnosis, treatment, and monitoring therapeutic efficacy.

Examination of the Relationship between Peripheral Inflammation Markers and Impulsivity and Aggression in Schizophrenia Patients Involved and Not Involved in Crime.

The aim of this study was to examine the relationship between peripheral inflammatory markers and aggression and impulsivity in schizophrenia patients with and without criminal histories. The study was conducted with patients with schizophrenia involved in crimes and hospitalized in the Forensic Psychiatry ward of Elazığ Fethi Sekin City Hospital and patients with schizophrenia not involved in crimes and hospitalized in the psychiatry ward of Elazığ Mental Health and Diseases Hospital. All participants completed the Buss-Waren Aggression Scale (BWAS), the Barratt Impulsiveness Scale-11 (BIS-11), and the Positive and Negative Symptom Scale (PANSS). Before treatment, venous blood samples were taken for laboratory measurements on the first day of hospitalization. All participants were male. The mean age of those involved in a crime was 39 ± 9.7 years, while the mean age of those not involved in a crime was 41.2 ± 10.7 years. The PANSS all subscale and total scores of the patients with schizophrenia who were involved in a crime were significantly higher than the group who were not involved (p values were p < 0.001, p = 0.001, p = 0.043, p = 0.001, respectively). The BWAS-physical aggression (p = 0.007) and total scores of the scale (p = 0.046) and BIS-11-inability to plan (p = 0.002) scores of the group involved in a crime were higher than the group not involved. As for laboratory parameters, MCH, MCHC, PDW, eosinophils, basophils, RDW-CV, and RDW-SD values were significantly higher in those involved in crime, while MPV, creatinine, albumin, and LDH values were lower. CRP and CRP/albumin values were significantly higher, while neutrophil/albumin values were significantly lower in those who committed murder in the first degree than those who committed other crimes. Based on our results, we found that inflammatory agents were significantly increased in forensic schizophrenia patients with high aggression scores. Significant correlations between some inflammatory factors and impulsivity and aggression scores and differences in these factors according to crime types showed that these factors might be related to violence and criminal behavior. There is a need for further large-scale studies on this subject at different stages of the disease.

Role of peripheral markers of inflammation in cognitive dysfunction in schizophrenic patients: a systematic review

IntroductionSchizophrenia (SCZ) is a chronic mental illness characterized by a rich and diverse symptomatology. A generalized cognitive deficit has been widely recognized among the symptoms of this disease. Several authors have studied the relationship between peripheral markers of inflammation and cognitive dysfunctions in order to explain the etiopathogeny of these disorders.ObjectivesThe aim of our study is to better comprehend the nature of the relation between peripheral markers of inflammation and cognitive dysfunctions.MethodsA systematic review of the literature was conducted following the guidelines provided by the PRISMA method. We performed a systematic search focused on two automated bibliographic databases: Pubmed and Google Scholar including the following keywords: “inflammation”, “schizophrenia”, “cognition”ResultsA total of 17 articles were included.Significant relations with cognitive function were reported with IL-6, IL-18, IL-2, IL-8, tumor necrosis factor α (TNF-α ) and chemokines. Memory was the cognitive domain where the most significant relations with cytokines were objectified.BDNF levels were correlated with cognitive tests in 5 studies of SCZ populations. The domains concerned were inhibition, flexibility, verbal fluency, verbal memory, attention, and processing speed.Elevated CRP in patients with SCZ was reported by all studies and a significant relation with cognition in 3 studies. This relations is objectified in the areas of memory, executive functions and processing speed.The relations between CRP, BDNF, cytokines and cognitive functions was inconsistent across studies.ConclusionsThe majority of the results observed during the review were in favor of a significant relation between CRP, BDNF and cytokines. Nevertheless, these results were not constant and heterogeneous. It would be interesting to better explore the nature of this relation through prospective studies in order to establish therapeutic perspectives.Disclosure of InterestNone Declared

Predicting unipolar and bipolar depression using inflammatory markers, neuroimaging and neuropsychological data: a machine learning study

IntroductionAbout 60% of bipolar disorder (BD) cases are initially misdiagnosed as major depressive disorder (MDD), preventing BD patients from receiving appropriate treatment. An urgency exists to identify reliable biomarkers for improving differential diagnosis (DD). Machine learning methods may help translate current knowledge on biomarkers of mood disorders into clinical practice by providing individual-level classification. No study so far has combined biological data with clinical data to provide a multifactorial predictive model for DD.ObjectivesDefine a predictive algorithm for BD and MDD by integrating structural neuroimaging and inflammatory data with neuropsychological measures (NM). Two different algorithms were compared: multiple kernel learning (MKL) and elastic net regularized logistic regression (EN).MethodsIn a sample of 141 subjects (70 MDD; 71 BD), two different models were implemented for each algorithm: 1) structural neuroimaging measures only (i.e. voxel-based morphometry (VBM), white matter fractional anisotropy (FA), and mean diffusivity (MD)); 2) VBM, FA, and MD combined with NM. In a subsample of 71 subjects (36 BD; 38 MDD), two similar models were implemented: 1) VBM, FA, and, MD combined with only NM; 2) VBM, FA, and MD combined with NM and peripheral inflammatory markers. Finally, the best model was selected for comparison with healthy controls (HC).ResultsOverall, the EN model based on all the modalities achieved the highest accuracy (AUC = 90.2%), outperforming MKL (AUC=85%). EN correctly classified BD and MDD with a diagnostic accuracy of 78.3%, sensitivity of 75%, and specificity of 81.6%. The most significant predictors of BD (variable inclusion probability (VIP) &gt; 80%) were the parahippocampal cingulate, interleukin 9, chemokine CCL5, posterior thalamic radiation, and internal capsule, whereas MDD was best predicted by chemokine CCL23, the anterior cerebellum, and the sagittal stratum. In contrast, NM did not help to differentiate between MDD and BD. However, they help to distinguish patients from HC. Psychomotor coordination and speed of information processing discriminated between MDD and HC (VIP&gt;90%), whereas fluency, working memory, and executive functions differentiated between BD and HC (VIP&gt;80%).ConclusionsIn summary, BD was predicted by a strong proinflammatory profile, whereas MDD was identified by structural neuroimaging data. A multimodal approach offers additional instruments to improve personalized diagnosis in clinical practice and enhance the ability to make DD.Disclosure of InterestNone Declared

The exploration of interoception construct in COVID-19 survivors

IntroductionThe new coronavirus disease (COVID-19) has important physical and mental health implications at short and long term. Some inflammatory parameters are implicated in the maintenance of psychiatric symptoms, especially those of anxiety and depression. Additionally, growing literature attributes a role to interoception in several mental health conditions.ObjectivesWe investigated the involvement of the interoception in COVID-19 survivors and its possible associations with psychopathological and inflammatory variables.MethodsOur study included 57 people surviving COVID-19 at one month follow-up after recovery. Individual interoceptive accuracy (IA) measure was obtained through heart-beat perception task. A measure of accuracy in external time perception (TA) was also obtained asking people to mentally produce a duration of 10s. Each participant completed State-Trait Anxiety Inventory - STAI-Y; Zung Self-Rating Depression Scale - ZSDS; Beck Depression Inventory - BDI-II; Impact of Events Scale - IES-R and Multidimensional Assessment of Interoceptive Awareness - MAIA. Peripheral inflammation markers were obtained in a subsample of 40 people by a blood sampling conducted at the time of admission and discharge from hospital. Correlation, regression and GLM analyses were performed with SPSS. Mediation analysis were performed with Hayes’ Process tool.ResultsTA is not associated with IA, symptomatological measures and bodily awareness. Trusting is the only aspect of body awareness associated with IA (p=.021). Noticing (p=.010), Not-distracting (p=.009), Not-worrying (p=.012) and Trusting (p=.001) predict anxiety psychopathology. Poor IA predict anxiety symptomatology (p=.004) and part of this effect is mediated by Trusting [Fig.1]. In the end, platelets count at the time of hospitalization negatively correlates with anxiety symptoms (p=.003).Image:ConclusionsCOVID-19 hospitalization could be considered a psychophysical traumatic experience which involved mental and physical health and the connection and integration between them. It’s necessary to deepen the different facets of body awareness and IA in post-covid stages and to study how interoceptive dimensions change over time. Further research is needed to investigate the specific role of platelets in prominent anxiety psychopathology detected in COVID-19 survivors, wondering about their possible involvement in the dysfunctional interoception process too.Disclosure of InterestNone Declared

Splitting the reward: Differences in inflammatory marker associations with neural connectivity between reward anticipation and reward outcome in adolescents at high risk for depression

BackgroundAdolescent depression is associated with both dysfunction in neural reward processing and peripheral inflammatory markers (PIMs), such as interleukin-6 (IL-6), C-reactive-protein (CRP), and tumor-necrosis factor alpha (TNFα). Few adolescent studies have examined neural-inflammatory marker associations and associated behavioral correlates, which would contribute to a better understanding of developmental processes linked to depression. Methods36 adolescents at high risk of depression completed an fMRI reward task (during anticipation and outcome), blood draw for PIMs (IL-6, CRP, and TNFα), and a behavioral task assessing motivation to expend effort. Analyses examined associations of task-dependent functional connectivity (FC; ventral striatum to frontal and default mode network brain regions), and if the interaction of PIMs and task-dependent FC predicted motivation to expend effort. ResultsFor anticipation contrast, TNFα was associated with increased task-dependent FC between the LVS and PCC/vmPFC. In moderation analyses, for anticipation contrasts, the combination of higher IL-6 and stronger FC (LVS-precuneus/PCC) was associated with lower motivation to expend effort, while for outcome contrasts, the combination of higher IL-6 and stronger FC (VS-precuneus/PCC) was associated with greater motivation to expend effort. ConclusionsOur findings in adolescents during an important developmental time period suggest that PIMs are directly linked to greater FC between the VS and DMN brain regions during win anticipation, consistent with prior studies. Effects of PIMs on motivation to expend effort may vary the strength/type of neural reward processing (anticipation or outcome), which could guide better understanding how inflammatory markers and neural reward substrates contribute to development of depression in high-risk adolescents.

Are serum levels of inflammatory markers associated with the severity of symptoms of bipolar disorder?

To explore the relationship between serum levels of inflammatory markers and symptomatic severity of bipolar disorder (BD). A cross-sectional study was conducted on 126 BD patients with current depressive episode (BDD), 102 BD patients with current mixed or (hypo)manic episode (BDM) and 94 healthy controls (HC). All participants were drug-naïve and had no current active physical illness associated with inflammatory response or history of substance abuse. Fasting serum levels of CRP, leptin (LEP), adiponectin (ADP), visfatin (VIS), TNF-α, IL-2, IL-6, IL-10, IL-17), and monocyte chemoattractant protein-1 (MCP-1) were measured with enzyme-linked immunosorbent assay (ELISA). Symptomatic severity of BD was assessed with HAMD-17 and YMRS. Generalized linear model was used to determine the association between the serum levels of inflammatory markers and symptomatic severity of BD. The serum levels of IL-6, IL-10 and IL-17, and the IL-6/IL-10 ratio were significantly lower in mild BDD than in HC. In moderate BDD, the serum levels of MCP, IL-6 and IL-17 were significantly lower than in HC. In severe BDD, the serum level of ADP, MCP-1, IL-10 and IL-17and the IL-17/IL-10 ratio were significantly lower than in HC. The serum levels of TNF-α and the IL-6/IL-10 ratio were significantly higher in mild BDM than in HC. In moderate BDM, the serum level of VIS, IL-2, and IL-17 were significantly higher than in HC, but the IL-6/IL-10 ratio was significantly lower than in control. In severe BDM, the serum levels of IL-6 and IL-17 and the ratios of IL-6/IL-10 and IL-17/IL-10 were significantly lower than in HC, but the neutrophil/lymphocyte ratio was significantly higher than in HC. In BDD, immune-inhibition is persistently predominant, while in mild-to-moderate BDM, immune system is activated but inhibited in severe BDM. The dynamic change of serum inflammatory markers suggests that alteration of peripheral inflammatory markers in BD is state-dependent instead of trait-marked.

Serum Inflammatory Markers and Integrity of the Superior Longitudinal Fasciculus and the Inferior Longitudinal Fasciculus in Schizophrenia, from Prodromal Stages to Chronic Psychosis-A Cross-Sectional Study.

Chronic subclinical inflammation is believed to be an important factor in the pathogenesis of schizophrenia. Meta-analyses confirm the presence of increased levels of peripheral inflammatory markers (IM) in schizophrenia and its prodromal stages. Peripheral cytokines may affect the brain microstructure through chronic activation of microglia. Disruptions in the integrity of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) are commonly seen in patients with schizophrenia spectrum disorders. We therefore attempted to verify in a cross-sectional study whether there is a correlation between levels of peripheral IM and the integrity of these brain regions in healthy controls, from prodromal states and first episode psychosis to long-term schizophrenia. The integrity of white matter was measured using diffusion tensor imaging. Despite a broad analysis of six IM (CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ), we did not find any correlations with the integrity of the SLF or ILF in any of the analyzed groups (after correction for multiple comparisons). In conclusion, our study does not support the existence of a link between disrupted levels of peripheral IM and reduced integrity of ILF and SLF in schizophrenia spectrum disorders. However, prospective studies are needed to verify this over a long period of time.

Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer’s disease: results from the DELCODE study

BackgroundNeuroinflammation constitutes a pathological hallmark of Alzheimer’s disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based beta-amyloid and neurodegeneration measures. We investigated experimental inflammation markers in serum and analyzed interrelations towards AD pathology features in a cohort with a focus on at-risk stages of AD.MethodsData of 74 healthy controls (HC), 99 subjective cognitive decline (SCD), 75 mild cognitive impairment (MCI), 23 AD relatives, and 38 AD subjects were obtained from the DELCODE cohort. A panel of 20 serum biomarkers was determined using immunoassays. Analyses were adjusted for age, sex, APOE status, and body mass index and included correlations between serum and CSF marker levels and AD biomarker levels. Group-wise comparisons were based on screening diagnosis and routine AD biomarker-based schematics. Structural imaging data were combined into composite scores representing Braak stage regions and related to serum biomarker levels. The Preclinical Alzheimer’s Cognitive Composite (PACC5) score was used to test for associations between the biomarkers and cognitive performance.ResultsEach experimental marker displayed an individual profile of interrelations to AD biomarkers, imaging, or cognition features. Serum-soluble AXL (sAXL), IL-6, and YKL-40 showed the most striking associations. Soluble AXL was significantly elevated in AD subjects with pathological CSF beta-amyloid/tau profile and negatively related to structural imaging and cognitive function. Serum IL-6 was negatively correlated to structural measures of Braak regions, without associations to corresponding IL-6 CSF levels or other AD features. Serum YKL-40 correlated most consistently to CSF AD biomarker profiles and showed the strongest negative relations to structure, but none to cognitive outcomes.ConclusionsSerum sAXL, IL-6, and YKL-40 relate to different AD features, including the degree of neuropathology and cognitive functioning. This may suggest that peripheral blood signatures correspond to specific stages of the disease. As serum markers did not reflect the corresponding CSF protein levels, our data highlight the need to interpret serum inflammatory markers depending on the respective protein’s specific biology and cellular origin. These marker-specific differences will have to be considered to further define and interpret blood-based inflammatory profiles for AD research.

The role of early life adversity and inflammation in stress-induced change in reward and risk processes among adolescents

BackgroundEarly life adversity (ELA) has long been associated with increased risk for stress-related psychopathology, particularly depression. The neuroimmune network hypothesis posits that ELA increases sensitivity to psychosocial stress, moderating the association between increases in peripheral markers of inflammation and decreases in reward outcomes linked to anhedonia and risk-taking behaviors. The present study examined this hypothesis in a sample of adolescents by using acute psychosocial stress to probe the role of inflammatory signaling in behavioral measures of reward and risk processing. Method80 adolescents [13.86 years (SD = 1.54); 45 % female], oversampled for ELA, underwent the Trier Social Stress Test for Children while providing blood samples immediately before and 60-minutes after stress onset. Blood samples were assayed for plasma IL-6. One hour before stress onset, and then 60 min after, participants completed computer-administered behavioral tasks measuring reward (Pirate Task) and risk (Balloon Analog Risk Task). ResultsELA moderated the association between increases in IL-6 and decreases in risk tolerance in pursuit of rewards (p = 0.003) and reward response bias (p = 0.04). Stress-induced increases in IL-6 were associated with decreases in pumps for rewards among adolescents exposed to high, relative to little or no, ELA. Further, greater IL-6 increases were associated with increases in bias toward high relative to low value rewards among adolescents with low adversity exposure but not among those exposed to higher adversity. ConclusionsThe present study provides the first evidence in a pediatric sample that ELA may alter the role of stress-induced inflammation in reward and risk processing, and may extend our understanding of why stress leads to depression in this high-risk population.

Biomarkers for predicting tumor response to PD-1 inhibitors in patients with advanced pancreatic cancer

ABSTRACT Pancreatic cancer is among the most lethal malignant neoplasms, and few patients with pancreatic cancer benefit from immunotherapy. We retrospectively analyzed advanced pancreatic cancer patients who received PD-1 inhibitor-based combination therapies during 2019–2021 in our institution. The clinical characteristics and peripheral blood inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and lactate dehydrogenase [LDH]) were collected at baseline. Chi-squared and Fisher’s exact tests were used to evaluate relationships between the above parameters and tumor response. Cox regression analyses were employed to assess the effects of baseline factors on patients’ survival and immune-related adverse events (irAEs). Overall, 67 patients who received at least two cycles of PD-1 inhibitor were considered evaluable. A lower NLR was independent predictor for objective response rate (38.1% vs. 15.2%, P = .037) and disease control rate (81.0% vs. 52.2%, P = .032). In our study population, patients with lower LDH had superior progression-free survival (PFS) and overall survival(OS) (mPFS, 5.4 vs. 2.8 months, P < .001; mOS, 13.3 vs. 3.6 months, P < .001). Liver metastasis was verified to be a negative prognostic factor for PFS (2.4 vs. 7.8 months, P < .001) and OS (5.7 vs. 18.0 months, P < .001). The most common irAEs were hypothyroidism (13.4%) and rash (10.5%). Our study demonstrated that the pretreatment inflammatory markers were independent predictors for tumor response, and the baseline LDH level and liver metastasis were potential prognostic markers of survival in patients with pancreatic cancer treated with PD-1 inhibitors.

Mental disorders associated with acute COVID-19: clinical picture, therapy approaches

The purpose is to study the structure of clinical manifestations of mental disorders in the acute period of COVID-19 among patients, who were hospitalized with a new coronavirus infection and their relations with the severity of the immune response, to assess the efficacy and safety profile of the spectrum of used psychopharmacotherapy. A study was conducted of patients, hospitalized to the department of infectious diseases and repurposed for COVID-19 clinical departments with a diagnosis of COVID-19 (compliance with the criteria for ICD-10: U07.1) from September 2020 to March 2021. Study design: single center opened retrospective cohort study. The main group is consisted of 72 patients, average age - 71 [56.0; 81.0] years, the part of women - 64.0%. The control group (n=2221) was formed from those hospitalized in the same period with a diagnosis of U07.1 without mental disorders during the hospitalization period, average age 62 [51.0; 72.0] years, the part of women - 48.7%. Mental disorders were diagnosed in accordance to ICD-10 criteria, the following peripheral markers of inflammation, that were evaluated: neutrophils, lymphocytes, platelets, ESR, C-reactive protein, interleukin; also coagulogram indicators: APTT, fibrinogen, prothrombin time, D-dimers. In the following range of mental disorders were identified: a depressive episode (ICD-10 F32) by 31 patients, by 22 - a disorder of adaptive reactions (ICD-10 F43.2), by 5 - delirium not caused by alcohol or other psychoactive substances (ICD-10 F05), by 14 - mild cognitive impairment caused by damage and disfunction of the brain or somatic diseases (ICD-10 F06.7). In comparison with the control group, these patients showed a statistically significant (p<0.001) increasing the level of inflammatory markers (CRP, IL-6) and changes in the coagulogram. and anxiolytic drugs were used most often. Regarding psychopharmacotherapy, drugs from the group of atypical antipsychotics - quetiapine was prescribed in 44% patients in average dose 62.5 mg per day, and Melatonin receptor type 1 and 2 agonist and antagonists of serotonin 5-HT2C receptors: agomelatine was prescribed in 11% patients in average dose 25 mg per gay. The results of the study confirm the heterogeneity of the structure of mental disorders in the acute form of coronavirus infection, revealing the relations between the clinical picture and laboratory parameters of the immune response to systemic inflammation. Recommendations are given for the choice of psychopharmacotherapy, in conformity with the peculiarities of pharmacokinetics and interaction with somatotropic therapy.

Glial-Neuronal Interaction in Synapses: A Possible Mechanism of the Pathophysiology of Bipolar Disorder.

Bipolar disorder (BD) is a severe and chronic psychiatric disorder that affects approximately 1-4% of the world population and is characterized by recurrent episodes of mania or hypomania and depression. BD is also associated with illnesses marked by immune activation, such as metabolic syndrome, obesity, type 2 diabetes mellitus, and cardiovascular diseases. Indeed, a connection has been suggested between neuroinflammation and peripheral inflammatory markers in the pathophysiology of BD, which can be associated with the modulation of many dysfunctional processes, including synaptic plasticity, neurotransmission, neurogenesis, neuronal survival, apoptosis, and even cognitive/behavioral functioning. Rising evidence suggests that synaptic dysregulations, especially glutamatergic system dysfunction, are directly involved in mood disorders. It is becoming clear that dysregulations in connection and structural changes of glial cells play a central role in the BD pathophysiology. This book chapter highlighted the latest findings that support the theory of synaptic dysfunction in BD, providing an overview of the alterations in neurotransmitters release, astrocytic uptake, and receptor signaling, as well as the role of inflammation on glial cells in mood disorders. Particular emphasis is given to the alterations in presynaptic and postsynaptic neurons and glial cells, all cellular elements of the "tripartite synapse," compromising the neurotransmitters system, excitatory-inhibitory balance, and neurotrophic states of local networks in mood disorders. Together, these studies provide a foundation of knowledge about the exact role of the glial-neuronal interaction in mood disorders.

Evaluation of inflammatory cytokines in drug-naïve major depressive disorder: A systematic review and meta-analysis.

Objective: Altered levels of peripheral inflammatory and proinflammatory cytokine markers affect the different clinical stages of major depressive disorder (MDD). A concrete understanding of the causal mechanism of MDD is a prerequisite in developing treatment strategies and preventive plans. Here we aimed to conduct an updated systematic review and meta-analysis of studies assessing the association of C-reactive protein (CRP), INF-γ, MCP-1, and TNF-α in the peripheral fluid of drug-naïve MDD patients and healthy controls (HCs). Methods: We extracted articles from PubMed, ProQuest, PsycINFO, Web of Science, and Scopus databases from inception until 14 February 2021, to find relevant studies. In this meta-analysis, we included a total of 23 eligible studies (1,366 MDD patients and 1,342 controls) in the final meta-analysis. The Cochran's chi-square Q-test and I2-index were applied to measure the heterogeneity and inconsistency of all combined results. We selected a random-effect model during the analysis and measured publication biases using the funnel plot. We performed Bonferroni adjustment for multiple testing. Results: We found a high level of TNF-α in MDD patients than in control subjects Standardized Mean Difference (SMD) with a random-effects model: 1.04, 95% CI: 0.69-1.39, z = 5.84, p < 0.001). The levels of CRP (SMD with a random-effects model: 0.18, 95% CI: -0.85-1.23, z = 0.35, p = 0.73), INF-ɤ (SMD with a random-effects model: -0.05, 95% CI: -2.72-2.62, z = 0.03, p = 0.97), and MCP-1 (SMD with a random-effects model: 0.70, 95% CI: -0.09-1.49, z = 1.73, p = 0.08) were not significantly varies between MDD patients and HCs. Conclusion: The present study findings suggest the upregulated level of peripheral TNF-α but not CRP, INF-γ, and MCP-1 involve in depression. The elevated inflammatory cytokines confirmed the inflammatory state of depression. Therefore, inflammatory cytokines might serve as potential risk assessment markers in MDD.

Retracted: Research on the Correlation of Peripheral Blood Inflammatory Markers with PCT, CRP, and PCIS in Infants with Community-Acquired Pneumonia.

[This retracts the article DOI: 10.1155/2022/9024969.].

The Tale of Depression and Inflammation Unraveled: On Depression Measurement Levels and Next Steps

The evidence for a link between the immune-inflammatory system and depression is highly robust. Strong pillars in the evidence include, among others, the observations that interferon treatment in a large proportion of those treated leads to clinically relevant depressive symptoms, and the large number of case-control studies summarized in meta-analyses pointing to elevated peripheral inflammatory markers in persons with a major depressive disorder versus those without. However, meta-analyses of inflammatory markers typically show small to moderate effect sizes and large heterogeneity.

Peripheral Inflammatory Markers TNF-α and CCL2 Revisited: Association with Parkinson’s Disease Severity

One of the major mediators of neuroinflammation in PD is tumour necrosis factor alpha (TNF-α), which, similar to other cytokines, is produced by activated microglia and astrocytes. Although TNF-α can be neuroprotective in the brain, long-term neuroinflammation and TNF release can be harmful, having a neurotoxic role that leads to death of oligodendrocytes, astrocytes, and neurons and, therefore, is associated with neurodegeneration. Apart from cytokines, a wide family of molecules with homologous structures, namely chemokines, play a key role in neuro-inflammation by drawing cytotoxic T-lymphocytes and activating microglia. The objective of the current study was to examine the levels of the serum TNF-α and CCL2 (Chemokine (C-C motif) ligand 2), also known as MCP-1 (Monocyte Chemoattractant Protein-1), in PD patients compared with healthy controls. We also investigated the associations between the serum levels of these two inflammatory mediators and a number of clinical symptoms, in particular, disease severity and cognition. Such an assessment may point to their prognostic value and provide some treatment hints. PD patients with advanced stage on the Hoehn-Yahr scale showed an increase in TNF-α levels compared with PD patients with stages 1 and 2 (p = 0.01). Additionally, the UPDRS score was significantly associated with TNF-α levels. CCL2 levels, however, showed no significant associations.