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It has been suggested that the immunological properties of cytokine primed PBSC may reflect the presence of altered levels of cellular components. In this study the changes induced in blood dendritic cell (DC) subsets following G-CSF mobilisation are analysed. Analysis of normal donors (n = 64) demonstrated considerable individual variation in the absolute numbers (×106/l) of resting blood CD11c- DC (1.2–26.2) and CD11c+ DC (0.9–34.7) as well as in the CD11c-/CD11c+ DC ratio (0.29–4.13). G-CSF therapy increased CD11c- DC numbers to above the normal range in all normal donors analysed (n = 6) and the CD11c-/CD11c+ ratio was also increased to >2.0 in all donors. Patients undergoing autologous PBSCT showed a heterogeneous response to mobilisation and although total DC and CD11c- DC numbers were increased in the majority (8/14), they remained within the normal range post mobilisation. The CD11c-/CD11c+ ratio decreased in 5/15 patients and only three patients had ratios >2.0 post mobilisation. Post G-CSF the DC from all normal donors and 13/14 patients had an immature phenotype. These results demonstrate that G-CSF mobilisation induces relatively consistent changes in the number and ratio of DC subsets in normal donors, but considerable variation is seen in the response of patients undergoing mobilisation for autologous PBSCT.Bone Marrow Transplantation (2002) 30, 733–740. doi:10.1038/sj.bmt.1703734 [ABSTRACT FROM AUTHOR]

Aim: Validated assessment tools are needed to identify clinically high risk for psychosis. This study aimed to validate the early recognition inventory ERIraos, which consists of the ERIraos Checklist for risk screening and the ERIraos Symptom List for a more thorough risk assessment in the Estonian language to detect psychotic prodromal symptoms., Methods: A prospective cohort study provided an opportunity to evaluate the characteristics of the ERIraos instrument in predicting the increased risk of a psychotic disorder in the future. The 177 study participants, aged 13-42 years old, were divided into groups without an increased risk and three risk groups with different risk severity levels based on the ERIraos Symptom List assessment., Results: The results indicated excellent inter-rater reliability for the ERIraos Symptom List total score. The ability of the ERIraos checklist to screen persons with an elevated psychosis risk was very good (ROC-AUC = 0.86). The capability of the ERIraos Symptom List scores to predict the probability of transitioning to psychosis within 2 years was very good (ROC-AUC = 0.83). Brief limited intermittent psychotic symptoms and observable behavioural and affective symptoms were statistically significant predictors of transition to psychosis. There were strong and statistically significant correlations between the ERIraos Symptom List scores and other clinical measures assessing functioning and psychopathology., Conclusions: The results of this study demonstrate the reliability and validity of the Estonian version of the ERIraos instrument and support the usability of ERIraos as a two-step tool for the early recognition of psychosis risk., (© 2024 John Wiley & Sons Australia, Ltd.)

Introduction: The reason for this study was void of a data-driven imminent risk assessment instrument for aggression in psychiatry clinics in Estonia. The predictive accuracy of the observer-rated Dynamic Assessment of Situational Aggression (DASA) has been repeatedly demonstrated. However, the research gap remains regarding a deeper conceptual understanding of the underlying latent structure of the DASA., Aim: Comprehensively evaluate the psychometric properties of the Estonian DASA version for cross-cultural clinical use., Method: We used a prospective repeated measure design and collected 6097 risk evaluations from 381 adult inpatients, 151 of whom committed 1013 aggressive incidents during the study., Results: The Estonian DASA version has acceptable inter-rater reliability (Kendall's τ = 0.74) and is a useful instrument with excellent predictive validity (AUC = 0.86) for identifying potentially aggressive inpatients. In our sample, the DASA has a bi-factorial structure which explains 83% of the total variance., Discussion: The adapted DASA has acceptable validity and reliability indices for measuring imminent aggression risk in adult inpatient units., Implications for Practice: Evidence-based risk assessment of aggression in psychiatric clinics enhances recognition of the signs of potentially aggressive behaviour in order to apply preventive actions and reduce aggression, thereby improving the quality of the care provided., (© 2024 John Wiley & Sons Ltd.)

Background: Schizophrenia (SCZ) patients exhibit 30% higher prevalence of metabolic syndrome (MetS) compared to the general population with its suboptimal management contributing to increased mortality. Large-scale studies providing real-world evidence of the underlying causes remain limited., Methods: To address this gap, we used real-world health data from the Estonian Biobank, spanning a median follow-up of ten years, to investigate the impact of genetic predisposition and antipsychotic treatment on the development of MetS in SCZ patients. Specifically, we set out to characterize antipsychotic treatment patterns, genetic predisposition of MetS traits, MetS prognosis, and body mass index (BMI) trajectories, comparing SCZ cases (n = 677) to age- and sex-matched controls (n = 2708)., Findings: SCZ cases exhibited higher genetic predisposition to SCZ (OR = 1.75, 95% CI 1.58-1.94), but lower polygenic burden for increased BMI (OR = 0.88, 95% CI 0.88-0.96) and C-reactive protein (OR = 0.88, 95% CI 0.81-0.97) compared to controls. While SCZ cases showed worse prognosis of MetS (HR 1.95, 95% CI 1.54-2.46), higher antipsychotic adherence within the first treatment year was associated with reduced long-term MetS incidence. Linear mixed modelling, incorporating multiple BMI timepoints, underscored the significant contribution of both, antipsychotic medication, and genetic predisposition to higher BMI, driving the substantially upward trajectory of BMI in SCZ cases., Interpretation: These findings contribute to refining clinical risk prediction and prevention strategies for MetS among SCZ patients and emphasize the significance of incorporating genetic information, long-term patient tracking, and employing diverse perspectives when analyzing real-world health data., Funding: EU Horizon 2020, Swedish Research Council, Estonian Research Council, Estonian Ministry of Education and Research, University of Tartu., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).)

Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature., (© 2023. Springer Nature Limited.)

The aim of this study was to evaluate how schizophrenia spectrum disorders (SSD) and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum levels of tryptophan (Trp) metabolites. A total of 112 adults (54 first-episode psychosis [FEP] patients and 58 control subjects [CSs]) participated in the study. The investigated changes in the metabolite levels appeared against a background of persistent increase in BMI and waist circumference among the patients. Regarding the kynurenine (KYN) pathway, the strongest changes were seen in AP-naïve FEP patients. Trp, KYN, kynurenic acid (KYNA), and anthranilic acid (ANT) levels were significantly reduced in blood samples from patients in the early stage of the disease. Furthermore, 3-OH-kynurenine (3-HK) and quinolinic acid (QUIN) levels were somewhat lower in these patients. Most of these changes in the KYN pathway became weaker with AP treatment. The levels of serotonin and its metabolite 5-HIAA tended to be higher at 5.1 years in patients showing the relation of elevated serotonin turnover to increased BMI and waist circumference. The similar trend was evident for the ratio between xanthurenic acid (XA) and KYNA with strong link to the elevated BMI. Altogether, the present study supports the role of Trp-metabolites in the development of obesity and metabolic syndrome in SSD patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Mental health disorders share substantial variance, prompting researchers to develop structural models that can capture both generalised psychopathology risk and disorder/symptom-specific variation. This study investigated the associations of the general and specific psychopathology factors with multiple personality trait hierarchy levels: broad domains, their facets and nuances (N = 1839 Estonian adults). A bi-factor model with a general 'p' factor and specific factors for internalising problems, thought disorders and substance use best represented psychopathology structure. Although traits' predictive accuracy varied across psychopathology factors, nuances (the lowest level personality units) provided higher predictive accuracy and higher discriminant validity than domains. For example, traits related to high vulnerability, depression and immoderation and low friendliness and achievement striving were most strongly associated with the p factor. Nuances may prove useful for predicting and understanding general and specific psychopathology forms., (© 2022 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd.)

The objective of this study was to evaluate how schizophrenia spectrum disorders and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum level of acylcarnitines (ACs), cytokines and metabolic biomarkers and to characterize the dynamics of inflammatory and metabolic changes in the early course of the disorder. A total of 112 adults participated in the study (54 patients with first-episode psychosis (FEP) and 58 control subjects). Biomolecule profiles were measured at the onset of first-episode psychosis and 0.6 years and 5.1 years after the initiation of APs. The results of the present study confirmed that specific metabolic-inflammatory imbalance characterizes AP-naïve patients. Short-term (0.6-years) AP treatment has a favourable effect on psychotic symptoms, as well as the recovery of metabolic flexibility and resolution of low-level inflammation. However, 5.1 years of AP treatment resulted in weight gain and increased serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ, hexoses, acetylcarnitine, short-chain ACs (C3, C4) and long-chain ACs (C16:2, C18:1, C18:2). In conclusion, despite the improvement in psychotic symptoms, 5.1 years of AP treatment was accompanied by a pronounced metabolic-inflammatory imbalance, which was confirmed by the presence of enhanced pro-inflammatory activity and increased obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites.

Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation phage display method to explore the link between antibody immune response to previously encountered antigens and spike (S) glycoprotein. By profiling the antibody response in COVID-19 naïve individuals with a diverse clinical history (including cardiovascular, neurological, or oncological diseases), we identified 15 highly antigenic epitopes on spike protein that showed cross-reactivity with antigens of seasonal, persistent, latent or chronic infections from common human viruses. We observed varying degrees of cross-reactivity of different viral antigens with S in an epitope-specific manner. The data show that pre-existing SARS-CoV-2 S1 and S2 cross-reactive serum antibody is readily detectable in pre-pandemic cohort. In the severe COVID-19 cases, we found differential antibody response to the 15 defined antigenic and cross-reactive epitopes on spike. We also noted that despite the high mutation rates of Omicron (B.1.1.529) variants of SARS-CoV-2, some of the epitopes overlapped with the described mutations. Finally, we propose that the resolved epitopes on spike if targeted by re-called antibody response from SARS-CoV-2 infections or vaccinations can function in chronically ill COVID-19 naïve/unvaccinated individuals as immunogenic targets to boost antibodies augmenting the chronic conditions. Understanding the relationships between prior antigen exposure at the antibody epitope level and the immune response to subsequent infections with viruses from a different strain is paramount to guiding strategies to exit the COVID-19 pandemic., (© 2022. The Author(s).)

Background: To enhance patient aggression management efficacy and to reduce the use of coercive interventions in inpatient psychiatric care, it is important to know the attitudes of all involved parties towards the aggression and its management., Aims: This study aimed to explore attitudes of the psychiatrists, nurses and inpatients toward the causes and management of patient aggression in Estonian psychiatric clinics. A frequency of aggressive behaviour experienced by professionals, the relationships between the attitudes, participation in coercion, and a frequency of aggression, were also identified., Methods: To assess attitudes towards the causes and management of patient aggression, the Management of Aggression and Violence Attitude Scale was implemented., Results: The survey comprised of 63 psychiatrists, 197 nurses and 199 inpatients. The patients and the professionals had similar as well as different attitudes toward aggression and its management. Patients expected professionals to take a more personal approach when aggression occurs; in some cases, allowing the patients to deal with negative emotions on their own but, if necessary, isolating or restraining the violent people., Conclusions: There is a need of training programs that focus on dealing patient aggression to foster a culture of safe, patient-centred care and to reduce aggression in psychiatric clinics.

Alterations in the expanded endocannabinoid system (eECS) and cell membrane composition have been implicated in the pathophysiology of schizophrenia spectrum disorders. We enrolled 54 antipsychotic (AP)-naïve first-episode psychosis (FEP) patients and 58 controls and applied a targeted metabolomics approach followed by multivariate data analysis to investigate the profile changes in the serum levels of endocannabinoids: 2-arachidonoylglycerol (2-AG) and anandamide, endocannabinoids-like N -acylethanolamines (NAEs: linoleoylethanolamide, oleoylethanolamide, and palmitoylethanolamide), and their dominating lipid precursor's phosphatidylcholines. Biomolecule profiles were measured at the onset of first-episode psychosis (FEP) and 0.6 years and 5.1 years after the initiation of AP treatment. The results indicated that FEP might be characterized by elevated concentrations of NAEs and by decreased 2-AG levels. At this stage of the disease, the NAE-mediated upregulation of peroxisome proliferator-activated receptors (PPARs) manifested themselves in energy expenditure. A 5-year disease progression and AP treatment adverse effects led to a robust increase in 2-AG levels, which contributed to strengthened cannabinoid (CB1) receptor-mediated effects, which manifested in obesity. Dynamic 2-AG, NAEs, and their precursors in terms of phosphatidylcholines are relevant to the description of the metabolic shifts resulting from the altered eECS function during and after FEP.

The primary objective of this study was to evaluate how schizophrenia (SCH) spectrum disorders and applied antipsychotic (AP) treatment affect serum level of amino acids (AAs) and biogenic amines (BAs) in the early course of the disorder. We measured 21 different AAs and 10 BAs in a sample of antipsychotic (AP)-naïve first-episode psychosis (FEP) patients (n = 52) at baseline, after 0.6-year as well as after 5.1-year treatment compared to control subjects (CSs, n = 37). Serum levels of metabolites were determined with AbsoluteIDQ p180 kit using flow injection analysis tandem mass spectrometry and liquid chromatography technique. Elevated level of taurine and reduced level of proline and alpha-aminoadipic acid (alpha-AAA) were established as metabolites with significant change in AP-naïve FEP patients compared to CSs. The following 0.6-year treatment restored these alterations. However, further continuous 5.1-year AP treatment changed the metabolic profile substantially. Significantly elevated levels of asparagine, glutamine, methionine, ornithine and taurine, alongside with decreased levels of aspartate, glutamate and alpha-AAA were observed in the patient group compared to CSs. These biomolecule profile alterations provide further insights into the pathophysiology of SCH spectrum disorders and broaden our understanding of the impact of AP treatment in the early stages of the disease.

Alterations in complex lipids may be involved in pathophysiology of schizophrenia spectrum disorders. Previously, we demonstrated importance of detecting lipid metabolism dysregulation by acylcarnitine (ACs) profile analysis in patients with first-episode psychosis (FEP). The aim of this study was to adopt lipidomics to identify serum glycerophospholipids (GPLs) and sphingomyelins (SMs) for describing FEP status before and after 7-month antipsychotic treatment. Using mass spectrometry and liquid chromatography technique, we profiled 105 individual lipids [14 lysophosphatidylcholines (LysoPCs), 76 phosphatidylcholines (PCs) and 15 SMs] in serum samples from 53 antipsychotic-naïve FEP patients, 44 of them were studied longitudinally and from 37 control subjects (CSs). Among the identified and quantified metabolites one LysoPC was elevated, and contrary the levels of 16 PCs as well as the level of one SM were significantly (p ≤ 0.0005) reduced in antipsychotic-naïve FEP patients compared to CSs. Comparison of serum lipids profiles of FEP patients before and after 7-month antipsychotic treatment revealed that 11 GPLs (2 LysoPCs, 9 PCs), and 2 SMs were found to be significantly changed (p ≤ 0.0005) in which GPLs were up-regulated, and SMs were down-regulated. However, no significant differences were noted when treated patient's serum lipid profiles were compared with CSs. Our findings suggest that complex lipid profile abnormalities are specifically associated with FEP and these discrepancies reflect two different disease-related pathways. Our findings provide insight into lipidomic information that may be used for monitoring FEP status and impact of the treatment in the early stage of the schizophrenia spectrum disorder.