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Goal of the ongoing work is to understand the dynamic interactions of neuroimmune components in the transition from normal brain function to dysfunction at the molecular, cellular levels in patients with schizophrenia especially deficite type. We have recruited and examined n=195 Non-deficit and n= 309 Deficit schizophrenia patients. In this study, we tested whether schizophrenia patients at different stages of illness might present alterations in the levels of HERV-K methylation. No significant differences in HERV-K methylation levels between D-SCZ and ND-SCZ as well as HCs were found. Our results indicate lower HERV-K methylation levels at early stages of schizophrenia. This difference might normalize with subsequent exacerbations of schizophrenia, likely due to the effects of anti-psychotics. Additionally we have tested a hypothesis whether variation in immune-inflammatory genes (IL-6, TGF-ß, CTLA-4 and CD28) might be associated with susceptibility to deficit schizophrenia. Polymorphisms in immune-inflammatory response genes are believed to impact schizophrenia susceptibility. However, it remains unknown whether immunogenetic factors play a role in the etiology of deficit schizophrenia (D-SCZ). Therefore, we genotyped four polymorphisms in genes encoding two immune system regulatory proteins (CTLA-4 rs231775 and CD28 rs3116496), interleukin-6 (IL6 rs1800795) and transforming growth factor-ß (TGFB1 rs1800470) in 513 schizophrenia patients and 374 controls. The CD28 rs3116496-CC genotype and C-allele were significantly more frequent in the whole group of patients and D-SCZ patients compared to controls. Our results indicate that the CD28 rs3116496 polymorphism might impact the risk of schizophrenia, especially D-SCZ. Immune-inflammatory alterations hold a great promise for better understanding disease etiopathology. [ABSTRACT FROM AUTHOR]

Introduction There is a scarcity of prospective studies addressing the influence of the methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms on antipsychotic-induced metabolic changes in first-episode schizophrenia (FES) patients. Objectives We aimed at investigating metabolic side effects of second-generation antipsychotics (SGAs) with respect to the MTHFR gene polymorphisms in FES patients. Methods Polymorphisms in the MTHFR gene (C677T and A1298C) were investigated with respect to changes in body mass index (BMI) and waist circumference (WC) together with serum levels of glucose, lipids, homocysteine, vitamin B12 and folate after 12 weeks of treatment with SGAs in 135 FES patients. Results The 677TT genotype was associated with significantly higher BMI, WC and serum levels of triglycerides, as well as significantly lower folate levels at baseline. Additionally, the 677T allele was associated with significantly lower folate levels at baseline. The 677CC homozygotes had significantly higher increase in BMI and serum levels of triglycerides. The 677TT genotype predicted significantly higher increase in homocysteine levels and significantly higher decrease in folate levels. These associations were also significant in the allelic analysis. Only the patients with the 677T allele had significantly lower folate levels and significantly higher homocysteine levels at the follow-up. The 677T allele was also related to significantly lower increase in WC. The 1298CC homozygotes had significantly higher weight gain in the course of treatment with SGAs. Conclusions The MTHFR gene polymorphisms might predict antipsychotic-induced weight gain in FES patients. In addition, the MTHFR C677T polymorphism might be also predictive with respect to other metabolic adversities of SGAs. [ABSTRACT FROM AUTHOR]

Introduction The influence of the immune deregulation on the risk and psychopathology of schizophrenia is increasingly recognized in the literature. Aim To assess the association between serum IL-1RA on schizophrenia psychopathology. Methods We recruited 88 schizophrenia patients (38 males and 49 females, mean age 38.12 ± 12.67 years) and 88 healthy adult control subjects (68 males, 20 females, mean age 40.63 ± 7.99 years). Lifetime psychopathology was evaluated using Operational Criteria for Psychotic Illness (OPCRIT) checklist, while current psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS). Serum samples were stored in aliquots at –80 °C. Serum levels of IL1-RA were measured using Immunoassay (ELISA). Results There were statistically significant differences between schizophrenia patients and healthy controls (median ± interquartile range: 350,81 ± 227.04 and 888.74 ± 762.63, respectively [pg/ml]) ( U Mann–Whitney test, Z = –7.99, P < 0.0001). There were no differences in serum IL1-RA levels between male and female among patients with schizophrenia ( U Mann–Whitney test, Z = –0.22, P = 0.82) nor among healthy control subjects ( U Mann–Whitney test, Z = –0.17, P = 0.86). Among schizophrenia patients, there was a trend-level association between IL-1RA serum level with negative symptoms (Spearman correlation coefficient, r = –0.23, P = 0.056), positive symptoms (Spearman correlation coefficient r = –0.22, P = 0.066), and on a statistically significant level with general symptoms (Spearman correlation coefficient r = –0.28, P = 0.018). Conclusion Serum IL1-RA level is higher in schizophrenia patients in comparison to healthy controls and it is associated with schizophrenia psychopathology. [ABSTRACT FROM AUTHOR]

Introduction Accumulating evidence indicates concordant epigenetic dysregulation in the brain and peripheral blood leukocytes in schizophrenia. It has also been found that stressful and traumatic events may alter DNA methylation; however, such studies have not been performed in schizophrenia patients. Objectives This study aimed at comparing LINE-1 methylation in first-episode schizophrenia (FES) patients and healthy control (HC) subjects with respect to the history of trauma. Methods We recruited 40 FES patients and 49 HC subjects matched for age, gender and body mass index (BMI). The early trauma self-report – short form (ETISR-SF) was administered to assess traumatic events. In addition to assessment of LINE-1 methylation, serum levels of homocysteine, folate and vitamin B12 were measured in all subjects. Results There was no significant difference in LINE-1 methylation between FES patients and HC subjects. However, LINE-1 methylation was significantly lower in FES patients with positive history of trauma when compared with FES patients and HC subjects with negative history of trauma (58.08±3.27% vs. 61.28±4.12%, p = 0.022 and 58.08±3.27% vs. 61.12±4.73%, p = 0.038, respectively). There was no significant difference in LINE-1 methylation between FES patients and HC subjects with negative history of trauma. There was a negative correlation between total trauma score and LINE-1 methylation (r = −0.390, p = 0.012). After controlling for confounding variables (age, gender, treatment duration, pack-year index, metabolic parameters), LINE-1 methylation was associated with total trauma score (p = 0.011). Conclusions Traumatic events might be associated with lower global DNA methylation in FES patients. [ABSTRACT FROM AUTHOR]

Introduction Humans learn how to behave both through rules and instructions (explicit learning) as well as through environmental experiences (implicit learning). It has been shown that instructions can powerfully control people's choices, often leading to a confirmation bias. Aim To explore confirmation bias with respect to cognitive functioning in healthy adult participants. Methods We recruited 25 healthy adult control subjects (9 males, 16 females, age 31.40 ± 6.08 years). Participants completed Repeatable Battery of Neuropsychological Status (RBANSS) as well as Instructed Version of Probabilistic Selection Task (IPST) (Doll et al., 2009). Results Based on the performance on IPST into two groups: a group with higher and lower susceptibility to confirmation bias. We found no difference between these groups with respect to any of the cognitive domains measured with RBANSS (immediate memory, visuospatial abilities, language, attention and delayed memory) ( U Mann-Whitney test, P > 0.05). Conclusion In healthy adults, susceptibility to confirmation bias is independent of cognitive functioning (immediate and delayed memory, visuospatial abilities, language and attention). [ABSTRACT FROM AUTHOR]

Social disability in persons diagnosed with mental disorder is one of the factors preventing them from achieving the broadly defined well-being, even when appropriate and effective treatment is applied. Improvement in the field of social disability is therefore one of the main challenges for the mental health and social welfare policy makers. The second version of the Groningen Social Disabilities Schedule (GSDS-II) is widely used in the assessment of social disability, however the relationship between its degree and many of the clinical and demographic factors have not been investigated thoroughly enough. The objective of the study is to assess the degree of social disability using GSDS-II as well as to analyze the relationship between the degree of social disability and clinical, social and demographic factors, in patients with a mental disorder diagnosis of F20–F48 according to ICD-10, aged 18–65, in a day ward and an inpatient ward settings. The paper presents the data gathered from a preliminary sample of 20 patients of both genders diagnosed with mental disorders who gave their informed consent to participate in the study, thus comprising 10% of the targeted total study sample. Our study, performed on a larger, targeted sample, will provide a better insight into the social functioning of persons with a burden of mental disorder. A precise presentation of the social disability shall improve the model of care offered to these persons. Any possible parallel studies in other countries, employing analogical methodology, could allow for a cross-national and cross-cultural comparison of the received outcomes. [ABSTRACT FROM AUTHOR]

Introduction Humans learn how to behave both through rules and instructions as well as through environmental experiences. It has been shown that instructions can powerfully control people's choices, often leading to a confirmation bias. Aim To compare learning parameters in reinforcement learning task with and without instructions. Methods We recruited 52 healthy adult control subjects (21 males, 31 females, age 30 ± 6.5 years). Participants completed Repeatable Battery of Neuropsychological Status (RBANSS). Twenty-seven participants completed additionally Probabilistic Selection Task (PST) while twenty-five participants completed Instructional Probabilistic Selection Task (IPST). To analyze learning parameters, we used Q-learning model with 3 parameters: learning rate due to positive and negative reinforcements as well as exploration-exploitation parameter. Results Both groups did not differ with respect to cognitive functioning measured with RBANSS (immediate and delayed memory, visuospatial abilities, language and attention); however, participants who completed PST had trend-level statistically faster learning rates due to positive ( P = 0.099) and negative reinforcements (0.057) in comparison to participants who completed IPST. Both groups did not differ with respect to exploration-exploitation parameter (0.409). Conclusion In healthy adults, interference of confirmation bias can influence learning speed independent of cognitive functioning (immediate and delayed memory, visuospatial abilities, language and attention). [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a chronic severe psychiatric disorder with multiple environmental and genetic determinants. Several reports indicate the possible role of immune system dysregulation in the pathogenesis of schizophrenia. An accumulating body of evidence indicates an association of schizophrenia and its psychopathology with altered cytokine production. The variation of the level of cytokines might be partly due to their functional gene polymorphism. Purpose: The study was carried out to investigate the association of schizophrenia with the following cytokine polymorphisms: IL-2 (-330T/G), IL-6 (-174G/C), IFN-gamma (+874 T/A), TGF-beta (+869 T/C and +915 G/C). Material and methods: We included 130 patients diagnosed with schizophrenia and 184 controls in our study. The patients were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic Illness (OPCRIT) checklist. The patients having history of traumatic brain injury, neurologic disorders, substance abuse or immune related diseases were excluded from the study by detailed medical examination. Results: The polymorphisms were in HWE both in the cases’ and controls’ groups. In single marker analysis, we did not find an association for the tested polymorphisms. Conclusion: Our data do not support the role of IL-2, IL-6, IFN-gamma and TGF-beta gene polymorphisms in the predisposition to schizophrenia in the Polish population. [Copyright &y& Elsevier]

Background: Neuregulin-1 (NRG1) may be an important factor in pathogenesis of schizophrenia due to its role in neurodevelopmental processes: myelination, neurotransmitter receptor expression and synaptic plasticity. NRG1 has been also implied to play role in cognitive impairments, which are considered to be endophenotypes of schizophrenia, i.e. subclinical, heritable and independent of clinical state traits associated with genetic susceptibility. Surprisingly, a recent meta-analysis (Dickinson, 2007) demonstrated that reliable and easy to administer Digit Symbol Coding Task (DSCT) discriminate people with schizophrenia from comparison individuals better than the more widely studied neuropsychological instruments. Purpose: The study was carried out to investigate the association of a polymorphisms of the NRG1 gene (rs62510682) and schizophrenia with respect to performance on DSCT. Material and methods: We included 103 patients diagnosed with schizophrenia according to ICD-10 criteria and 578 controls in our study. The patients were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic Illness (OPCRIT) checklist. DSCT was administered to 80 patients. Results: The polymorphisms were in HWE both in the cases’ and controls’ groups. In single marker analysis, we did not find an association for the SNP tested. However; we have found that T allel carriers (TT and/or GT genotype) performed worse than G allel carriers (p=0.4) suggesting weaker cognitive processing efficiency. Conclusion: Our data do not support the role of the NRG1 gene polymorphism (rs62510682) in the predisposition to schizophrenia; however, the studied SNP might be considered to be a risk factor for cognitive impairment in schizophrenia. [Copyright &y& Elsevier]

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of psychosis and subthreshold psychotic symptoms commonly referred to as psychotic-like experiences (PLEs). The exact mechanisms linking the HPA axis responses with the emergence of PLEs remain unknown. The present study aimed to explore real-life associations between stress, negative affect, salivary cortisol levels (a proxy of the HPA axis activity) as well as PLEs together with their underlying cognitive biases (i.e., threat anticipation and aberrant salience). The study was based on the experience sampling method scheduled over 7 consecutive days in the sample of 77 drug-naïve, young adults (18-35 years). The saliva samples were collected with each prompt to measure cortisol levels. A temporal network analysis was used to explore the directed associations of tested variables. Altogether, 3234 data entries were analyzed. Data analysis revealed that salivary cortisol levels did not directly predict next-moment fluctuations of PLEs. However, higher salivary cortisol levels were associated with higher next-moment levels of PLEs through the effects on threat anticipation and negative affect. In turn, PLEs appeared to predict cortisol levels through the effects on negative affect and event-related stress. Negative affect and threat anticipation were the most central nodes in the network. There might be bidirectional associations between the HPA axis responses and PLEs. Threat anticipation and negative affect might be the most important mediators of these associations. Interventions targeting these mediators might hold promise for disrupting the connection between the HPA axis dysregulation and PLEs.

Background: The European Psychiatric Association (EPA) is an organization that speaks on behalf of its individual members and members of National Psychiatric Associations (NPAs). The aim of this study to identify and investigate current contents of ethical codes and practices in the countries belonging to EPA., Methods: The study is an expert survey sent out to 44 representatives of 30 NPAs covering the following topics: the existence of national bodies dealing with ethical issues in psychiatry, the availability of documents relevant to ethical issues, the types of ethical issues addressed at the national level, and the current and envisaged ethical debates., Results: Out of 44 experts invited to participate in the study, 31 NPAs from 30 countries responded (response rate 70.45%). In the majority of countries, the general mission statement serves as the main document covering ethical issues in psychiatry. Most frequently, internal documents were reported to address medical malpractice, workplace bullying, plagiarism, academic fraud, sexual abuse, and discrimination/racism. Furthermore, internal documents cover the ethical assessment of potentially controversial procedures, including psychosurgery, euthanasia, and pregnancy termination. The most important topics for debate at the level of NPAs/EPA were associated with violations of clinical practice standards and human rights., Conclusions: NPAs are active in the field of professional ethics, defining ethical standards related to interactions among professionals and services provided by mental health care professionals. Future collaboration of NPAs, under the umbrella of the EPA, could allow to develop a database of local ethical documents that would be translated into English and accessible to all EPA members.

The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries.

Background: Psychotic-like experiences (PLEs) are associated with a variety of psychopathological symptoms. However, it remains unknown which dimensions of psychopathology are most closely related to the occurrence of PLEs. In this study, we aimed to analyze the association of PLEs with various domains of psychopathology., Methods: A total of 1100 nonclinical adults (aged 18-35 years, 51.4% females) with a negative history of psychiatric treatment were surveyed. Assessment of psychopathology was performed using self-reports. Symptoms associated with PLEs were explored as continuous variables and based on clinically relevant thresholds using two separate network analyses., Results: In both network analyses, PLEs were directly connected to obsessive-compulsive disorder (OCD) symptoms, manic symptoms, depressive symptoms, and attention-deficit/hyperactivity disorder (ADHD) symptoms. Anxiety symptoms were associated with PLEs only in the network based on threshold scores. Importantly, edge weight for the connection of PLEs and OCD symptoms was significantly higher compared to edge weights of all other direct connections of PLEs with psychopathology in both networks. Edge weight for the connection between PLEs and manic symptoms was significantly higher compared to edge weights for direct connections of PLEs with depressive and ADHD symptoms in the network based on continuous scores of psychopathological symptoms. Edge weights of direct connections of PLEs with depressive, anxiety, and ADHD symptoms did not differ significantly in both networks., Conclusions: Our findings indicate that PLEs are associated with multiple domains of psychopathology. However, these phenomena are most strongly associated with OCD symptoms regardless of their severity threshold.

Objective: The pathogenesis of schizophrenia is multidimensional and intensively studied. The gut-brain axis disturbances might play a significant role in the development of schizophrenia., Methods: We compared the gut microbiota of 53 individuals with schizophrenia and 58 healthy controls, using the 16S rRNA sequencing method. Individuals with schizophrenia were assessed using the following scales: the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Social and Occupational Functioning Assessment Scale and the Repeatable Battery for the Assessment of Neuropsychological Status., Results: No significant between-group differences in α-diversity measures were observed. Increased abundance of Lactobacillales (order level), Bacilli (class level) and Actinobacteriota (phylum level) were found in individuals with schizophrenia regardless of potential confounding factors, and using two independent analytical approaches (the distance-based redundancy analysis and the generalised linear model analysis). Additionally, significant correlations between various bacterial taxa (the Bacteroidia class, the Actinobacteriota phylum, the Bacteroidota phylum, the Coriobacteriales order and the Coriobacteria class) and clinical manifestation (the severity of negative symptoms, performance of language abilities, social and occupational functioning) were observed., Conclusions: The present study indicates that gut microbiota alterations are present in European patients with schizophrenia. The abundance of certain bacterial taxa might be associated with the severity of negative symptoms, cognitive performance and general functioning. Nonetheless, additional studies are needed before the translation of our results into clinical practice.

Background: Accumulating evidence indicates that a variety of distal and proximal factors might impact a risk of suicide. However, the association between both groups of factors remains unknown. Therefore, in the present study, we aimed to investigate the interplay between distal and proximal correlates of the current suicidal ideation., Methods: A total of 3,000 individuals (aged 18-35 years, 41.7% males), who had reported a negative history of psychiatric treatment, were enrolled through an online computer-assisted web interview. Self-reports were administered to measure: (a) distal factors: a history of childhood trauma (CT), reading disabilities (RDs), symptoms of attention-deficit/hyperactivity disorder (ADHD), lifetime history of non-suicidal self-injury (NSSI), lifetime problematic substance use as well as family history of schizophrenia and mood disorders; (b) proximal factors: depressive symptoms, psychotic-like experiences (PLEs), and insomnia; and (c) sociodemographic characteristics., Results: Suicidal ideation was directly associated with unemployment, being single, higher level of RD, lifetime history of NSSI as well as higher severity of PLEs, depression, and insomnia. The association of distal factors with suicidal ideation was fully (a history of CT and symptoms of ADHD) or partially (a history of NSSI and RD) mediated by proximal factors (PLEs, depression, and insomnia)., Conclusions: Main findings from this study posit the role of distal factors related to neurodevelopmental disorders, CT and NSSI in shaping suicide risk. Their effects might be partially or fully mediated by depression, PLEs, and insomnia.

Background: The balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD., Methods: We searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD., Results: We included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances., Conclusions: An imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

Background: There is a growing number of studies showing interactions between genetic polymorphisms associated with dopaminergic neurotransmission and traumatic life events (TLEs) on a risk of psychotic-like experiences (PLEs). Anomalous self-experiences (ASEs) have been associated both with TLEs as well as with PLEs. However, it remains unknown what is the role of ASEs in the complexity of gene-environment interactions on the emergence of PLEs., Patients and Methods: We included 445 young adults-university students from three big cities in Poland. We used the Traumatic Events Checklist to assess TLEs, the Inventory of Psychotic-Like anomalous self-experiences in order to measure ASEs, and the Prodromal Questionnaire (PQ16) to record the level of PLEs. The following gene polymorphisms, related to dopaminergic neurotransmission, were determined: the catechol-O-methyltransferase (COMT) rs4680 polymorphism, the dopamine D2 receptor (DRD2) rs6277 polymorphism, and the dopamine transporter 1 (DAT1) rs28363170 polymorphism., Results: There was a significant effect of the interaction between the DAT1 polymorphism, a severity of ASEs, and a history of TLEs on the level of PLEs. Among the DAT1 10R/10R homozygotes with low level of ASEs, a severity of PLEs was significantly higher in individuals with a history of any TLEs. Higher scores of the PQ16 were associated with a greater severity of ASEs both in the DAT1 9R allele carriers and the DAT1 10R/10R homozygotes., Conclusion: Our findings imply that genetic liability related to aberrant dopamine transport might impact the association between TLEs and PLEs in subjects with high levels of ASEs.

Background: Childhood traumatic events are risk factors for psychotic-like experiences (PLEs). However, the mechanisms explaining how trauma may contribute to the development of PLEs are not fully understood. In our study, we investigated whether cannabis use and cognitive biases mediate the relationship between early trauma and PLEs., Methods: A total sample of 6,772 young adults (age 26.6 ± 4.7, 2,181 male and 3,433 female) was recruited from the general population to participate in an online survey. We excluded 1,158 individuals due to a self-reported lifetime diagnosis of any mental disorder. The online survey included selected items from the following questionnaires: Traumatic Experience Checklist (TEC, 3 items), Childhood Experience of Care and Abuse Questionnaire (CECA.Q, 3 items), Cannabis Problems Questionnaire (CPQ, 10 items), Davos Assessment of Cognitive Biases Scale (DACOBS-18, 9 items), and Prodromal Questionnaire-16 (PQ-16). Mediation analyses were performed with respect to different categories of traumatic experiences (emotional, physical and sexual abuse as well as emotional neglect)., Results: Our results showed significant associations of any time of childhood trauma with higher scores of cannabis use (CPQ), cognitive biases (DACOBS), and PLEs (PQ-16) (p < 0.001). We found a direct effect of childhood trauma on PLEs as well as significant indirect effect mediated through cannabis use and cognitive biases. All models tested for the effects of specific childhood adversities revealed similar results. The percentage of variance in PQ-16 scores explained by serial mediation models varied between 32.8 and 34.2% depending on childhood trauma category., Conclusion: Cannabis use and cognitive biases play an important mediating role in the relationship between childhood traumatic events and the development of PLEs in a nonclinical young adult population.

Introduction: Non-pharmacological interventions preferably precede pharmacological interventions in acute agitation. Reviews of pharmacological interventions remain descriptive or compare only one compound with several other compounds. The goal of this study is to compute a systematic review and meta-analysis of the effect on restoring calmness after a pharmacological intervention, so a more precise recommendation is possible., Method: A search in Pubmed and Embase was done to isolate RCT's considering pharmacological interventions in acute agitation. The outcome is reaching calmness within maximum of 2 h, assessed by the psychometric scales of PANSS-EC, CGI or ACES. Also the percentages of adverse effects was assessed., Results: Fifty-three papers were included for a systematic review and meta-analysis. Most frequent studied drug is olanzapine. Changes on PANNS-EC and ACES at 2 h showed the strongest changes for haloperidol plus promethazine, risperidon, olanzapine, droperidol and aripiprazole. However, incomplete data showed that the effect of risperidon is overestimated. Adverse effects are most prominent for haloperidol and haloperidol plus lorazepam., Conclusion: Olanzapine, haloperidol plus promethazine or droperidol are most effective and safe for use as rapid tranquilisation. Midazolam sedates most quickly. But due to increased saturation problems, midazolam is restricted to use within an emergency department of a general hospital., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Radicalization is a process, by which individuals adopt extreme political, social and religious ideation that leads to mass violence acts. It has been hypothesized that mental health characteristics might be associated with a risk of radicalization. However, a qualitative synthesis of studies investigating the relationship between mental health and radicalization has not been performed so far. Therefore, we aimed to perform a systematic review of studies examining the association between mental health characteristics and the risk of radicalization. Two reviewers performed an independent search of online databases from their inception until 8 th April 2018 and 12 publications met eligibility criteria. There were several methodological limitations across the majority of eligible publications, including doubtful sample representativeness, use of diagnostic procedures without personal assessment of mental health status or lack of standardized tools for assessment of mental health. Representative cross-sectional studies revealed that depressive symptoms might be associated with radicalization proneness. However, it remains unknown whether depressive symptoms are associated with resilience or vulnerability to radicalization. Another finding from our systematic review is that several personality traits might predispose to develop extreme ideation. Finally, there is some evidence that lone-actors might represent a specific subgroup of subjects with extreme beliefs which can be characterized by high prevalence of psychotic and/or mood disorders. In conclusion, this systematic review indicates that caution should be taken on how the association between 'mental health' and 'radicalization' is being claimed, because of limited evidence so far, and a number of methodological limitations of studies addressing this issue., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)