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Depression is a heterogenous diagnostic construct; however, dynamic interactions between specific depressive symptoms across their qualitatively different profiles remain largely unknown. The study aimed to recognize the most prevalent profiles of depressive symptoms and assess their dynamics in young adults without a history of psychiatric treatment. Depressive symptoms were recorded using the Patient Health Questionnaire-9 (PHQ-9). The data were assessed for all theoretical and empirical combinations of depressive symptoms in participants with a positive screening for depression. The profiles identified in the majority of participants were analyzed using partial correlation and Bayesian networks. Data from 3583 individuals with a positive screening for depression were analyzed. Out of 382 theoretical profiles, 150 profiles (39.3%) were present in this dataset. The majority of participants (56.8%) showed 4 profiles of depressive symptoms including the profile with all depressive symptoms present, the profile without suicidal ideation, the profile without psychomotor impairment, and the profile without both psychomotor impairment and suicidal ideation. The profiles differed largely in terms of their dynamics and symptoms that are necessary to activate the whole network. The network characteristics within specific profiles did not differ significantly across the level of difficulties attributable to depressive symptoms. Our findings indicate that depression emerging in young adults shows a limited number of symptom profiles. However, dynamics of depressive symptoms differs largely between specific profiles regardless of functional impairment indicating the need to personalize therapeutic approaches. Future studies should further disentangle the heterogeneity of depressive symptoms, e.g., by dissecting the symptoms that are combined together by single PHQ-9 items (i.e., hypersomnia and insomnia; psychomotor agitation and retardation)., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Several studies have shown that social isolation and loneliness are associated with the occurrence of psychotic experiences. However, dynamics of these phenomena in people with subclinical experiences, commonly referred to as psychotic-like experiences (PLEs), remains largely unknown. Therefore, in this study we performed a temporal network analysis to model dynamic predictions between social isolation, loneliness, negative affect, social stress, and PLEs., Methods: A total of 77 drug-naïve individuals with PLEs from a transdiagnostic sample were enrolled. Data were obtained using the experience sampling method (ESM). The ESM questionnaires were delivered during 7 consecutive days (6 assessments per day). Therefore, 3234 data entries were analyzed., Results: Social isolation predicted next-moment emergence of PLEs through the effects on loneliness and negative affect. Also, PLEs appeared to predict next-moment loneliness, but not social isolation, through the effects on negative affect. Social stress did not predict any variables in the network. However, it was predicted by previous-moment PLEs and social isolation. Negative affect had the highest in-strength and out-strength centrality., Conclusions: Findings from the present study indicate that social isolation might predict the emergence of PLEs through the effects of momentary loneliness and negative affect. Also, loneliness might be bidirectionally associated with PLEs. Interventions targeting negative affect and social isolation might be beneficial in people with PLEs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest related to the present study., (Copyright © 2024. Published by Elsevier Inc.)

Background/objectives: The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with various mental disorders. One of the most commonly described parameters of HPA axis functioning is the cortisol awakening response (CAR). To date, few studies have been conducted on the relationship between personality disorders and CAR. The present study aimed to compare the CAR between individuals with personality disorders and healthy controls. Moreover, the study aimed to assess the association of CAR with cognitive biases and psychopathological symptoms in people with personality disorders., Methods: A total of 43 individuals with personality disorders and 45 healthy controls were enrolled. Participants completed questionnaires measuring the severity of depressive symptoms, anxiety, cognitive biases, and psychotic-like experiences. Cortisol levels were measured in four morning saliva samples: immediately after awakening, and after 15, 30, and 45 min., Results: A significantly lower CAR was found among individuals with personality disorders, even after adjustment for age, sex, and the level of education. However, the receiver operating characteristic (ROC) curve analysis showed a relatively low area under the curve (AUC = 0.362). Furthermore, a significant negative correlation was observed between the CAR and the level of external attribution bias among individuals with personality disorders. No significant associations of the CAR with psychopathological symptoms and other cognitive biases were observed., Conclusions: Findings from this study indicate that the HPA axis activity might be altered in personality disorders. However, the clinical utility of this observation needs further studies in larger samples. External attribution might be related to the HPA axis alterations in this population.

The aim of this study was to investigate the relationship between gut microbiota and major depressive disorder (MDD) and schizophrenia (SCZ) by comparing 36 inpatients with these conditions to 29 healthy controls (HC) matched for age, sex, and body mass index (BMI). Individuals with SCZ exhibited greater microbiota richness compared to HC (FDR P(Q)=0.028). Taxonomically, while no significant differences were observed between the microbiota of MDD and SCZ patients in a head-to-head comparison, both patient groups differed significantly when compared to HC. Interestingly, besides common patterns (such as a higher abundance of Erysipelotrichaceae UCG-003 and Streptococcus, and a lower abundance of Lachnospiraceae ND3007 group), unique patterns were exhibited only in MDD (with a higher abundance of Anaerostipes, Q=0.004) or SCZ (with a higher abundance of Sutterella, Q=0.001, and a lower abundance of Clostridium sensu stricto 1, Q=0.002). The Random Forest algorithm identified Ruminococcus torques group, Lachnospiraceae UCG-001, and Erysipelotrichaceae UCG-003 as highly discriminative features for both SCZ and MDD, while Suturella and Holdemania were unique features for SZC, and Lachnospiraceae genus CAG-56 and Anaerostipes for MDD. Additionally, between 50 % and 60 % of the differentially abundant taxa were found among the top 10 influential features in the RF models. In conclusion, while no significant differences were found between the microbiota of MDD and SCZ patients, distinct microbial patterns were found in each group when compared to HC. The study did not confirm universal microbial biomarkers reported in other studies but showed that the observed differences concern the bacteria associated with inflammation, the production of short chain fatty acids (SCFA), and the synthesis of metabolites linked to mental health (lactic acid, gamma-aminobutyric acid - GABA). The application of machine learning holds promise for further understanding the complex relationship between microbiota and these psychiatric disorders. The observed results should be treated with caution due to the limitations of this study (mainly sample size), therefore further researches under standardized environmental conditions with consistent analytical and bioinformatics approaches are warranted., Competing Interests: Declaration of Competing Interest Igor Łoniewski is probiotic company shareholders, Mariusz Kaczmarczyk and Konrad Podsiadło are employed by probiotic company, Karolina Skonieczna-Żydecka receives remuneration from probiotic company. The funding sources had no role in concept design, selection of articles, the decision to publish, or the preparation of the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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/objectives: Problematic online gaming and gambling tend to co-occur. The exact mechanisms underlying this phenomenon and the potential effects of gender differences remain unknown. This study aimed to identify the early clustering patterns of problematic online gaming and gambling in a community sample of young adults without a lifetime history of psychiatric treatment., Methods: Data were collected through an online survey and analyzed using partial correlations and Bayesian networks., Results: Altogether, 1441 individuals (aged 18-40 years, 51.4% females) participated in the survey. Both problematic online behaviors were weakly interrelated, suggesting that they serve as distinct constructs. Men's networks appeared to be more complex and had significantly higher global connectivity. Moreover, men and women differed with respect to the specific nodes that bridged both constructs. In men, the bridge nodes were "being criticized because of betting or being told about gambling problems", "loss of previous interests due to gaming", "deceiving other people because of gaming", and "health consequences of gambling". Among women, the bridge nodes were "feeling guilty because of gambling", "loss of previous interests because of gaming", "social consequences of gaming", and "continued gaming problems with other people". In men, the strongest edge was found between "borrowing money/selling anything to gamble" and "financial problems because of gambling", while in women, the strongest edge appeared between "betting more than afforded to be lost" and "tolerance symptoms of gambling"., Conclusions: The findings indicate that problematic online gaming and gambling tend to emerge in different ways among men and women. Therapeutic interventions should be planned considering gender differences.

Felt presence (FP) is a phenomenon that might appear in individuals with mental and neurological disorders as well as those without any specific morbidity. Some studies have indicated that FP is closely related to psychotic symptomatology. Yet, the mechanisms underlying its occurrence remain largely unknown. The present study aimed to disentangle as to whether FP is associated with widely known risk factors of psychosis. Data from three independent samples of non-clinical young adults were analyzed. Self-reports were administered to assess psychopathological symptoms (samples 1 - 3), neurodevelopmental risk factors for psychosis (sample 1), social defeat components (sample 2), childhood trauma and loneliness (sample 3). A total of 4782 individuals were surveyed across all three samples. Unadjusted analyses showed that the following factors are associated with higher odds of FP: obstetric complications, childhood trauma, non-right handedness, a lower education level, unemployment, minority status, humiliation, perceived constraints, and loneliness. However, only minority status and a lower level of education were associated with higher odds of FP after adjustment for other psychopathological symptoms, age, and gender. Importantly, hallucination-like experiences across all recorded modalities and paranoia were associated with higher odds of FP in all samples. Depressive symptoms were weakly associated with FP in two samples. Findings from the present study suggest that the majority of known risk factors for psychosis contribute to the emergence of FP through the effects on psychotic experiences. Low educational attainment and minority status might be the only risk factors independently contributing to the emergence of FP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maciaszek, Senczyszyn, Rejek, Bielawski, Błoch and Misiak.)

Abstract: Schizophrenia is a debilitating mental health disorder that imposes profound economic, societal, and personal burdens. The negative symptoms of schizophrenia ( i.e. , blunted affect, alogia, anhedonia, asociality, and avolition) are highly prevalent and pervasive in the psychotic disorder and pose significant resistance to available treatment options. Traumatic childhood experiences are strongly linked with the risk of developing schizophrenia. Most prior studies have primarily focused on positive symptoms of schizophrenia ( e.g. , hallucinations and delusions), whereas less attention has been given to negative symptoms. The current study investigated the relationship between childhood trauma ( i.e. , physical abuse, sexual abuse, and emotional abuse and neglect) and negative symptoms in a sample of schizophrenia outpatients and healthy controls ( n = 159 participants, including 99 patients with schizophrenia). The observations from the current study revealed that schizophrenia patients experienced a significantly greater degree of childhood trauma and negative symptoms than the control individuals. The results of the current study also indicated that more severe experiences of total childhood trauma ( i.e. , summation of all trauma types), physical abuse, and emotional neglect may increase the risk of schizophrenia patients reporting negative symptoms. However, childhood sexual and emotional abuse was found to have no impact on the degree of negative symptoms experienced by schizophrenia patients. Implications and limitations of the current study are discussed. In conclusion, we found that the severity of overall childhood trauma, physical abuse, and emotional neglect may play an important role in increasing the likelihood of schizophrenia patients reporting negative symptoms., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Adverse childhood experiences (ACEs) are a well-known risk factor of schizophrenia. Moreover, individuals with schizophrenia are likely to use maladaptive stress coping strategies. Although it has been reported that a history of ACEs might be associated with a pro-inflammatory phenotype in patients with schizophrenia, the interacting effect of coping styles on this association has not been tested so far. In the present study, we aimed to investigate the levels of immune-inflammatory markers in patients with schizophrenia and healthy controls (HCs), taking into consideration a history of ACEs and coping strategies. Participants included 119 patients with schizophrenia and 120 HCs. Serum levels of 26 immune-inflammatory markers were determined. A history of any categories of ACEs was significantly more frequent in patients with schizophrenia. Moreover, patients with schizophrenia were significantly more likely to use emotion-focused coping and less likely to use active coping strategies compared to HCs. The levels of interleukin(IL)-6, RANTES, and tumor necrosis factor-α (TNF-α), appeared to be elevated in patients with schizophrenia after adjustment for potential confounding factors in all tested models. Participants reporting a history of any ACEs had significantly higher levels of TNF-α and IL-6. No significant main and interactive effects of active strategies as the predominant coping on immune-inflammatory markers with altered levels in patients with schizophrenia were found. Findings from the present study indicate that ACEs are associated with elevated TNF-α and IL-6 levels regardless of schizophrenia diagnosis and predominant coping styles., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The etiology of schizophrenia (SCZ), an incredibly complex disorder, remains multifaceted. Literature suggests the involvement of oxidative stress (OS) in the pathophysiology of SCZ., Objectives: Determination of selected OS markers and brain-derived neurotrophic factor (BDNF) in patients with chronic SCZ and those in states predisposing to SCZ-first episode psychosis (FP) and ultra-high risk (UHR)., Materials and Methods: Determination of OS markers and BDNF levels by spectrophotometric methods and ELISA in 150 individuals (116 patients diagnosed with SCZ or in a predisposed state, divided into four subgroups according to the type of disorder: deficit schizophrenia, non-deficit schizophrenia, FP, UHR). The control group included 34 healthy volunteers., Results: Lower activities of analyzed antioxidant enzymes and GSH and TAC concentrations were found in all individuals in the study group compared to controls (p < 0.001). BDNF concentration was also lower in all groups compared to controls except in the UHR subgroup (p = 0.01). Correlations were observed between BDNF, R-GSSG, GST, GPx activity, and disease duration (p < 0.02). A small effect of smoking on selected OS markers was also noted (rho<0.06, p < 0.03)., Conclusions: OS may play an important role in the pathophysiology of SCZ before developing the complete clinical pattern of the disorder. The redox imbalance manifests itself with such severity in individuals with SCZ and in a state predisposing to the development of this psychiatric disease that natural antioxidant systems become insufficient to compensate against it completely. The discussed OS biomarkers may support the SCZ diagnosis and predict its progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Schizophrenia is associated with chronic subclinical inflammation and decreased integrity of the corpus callosum (CC). Our previous study showed associations between peripheral IL-6 levels and the integrity of the CC. Epigenetic studies show associations between methylation of the genes related to immunological processes and integrity of the CC., Aim: To investigate correlations between methylation status of IL-6 promotor and peripheral IL-6 levels and the integrity of the CC in schizophrenia., Material and Methods: The participants were 29 chronic schizophrenia patients (SCH) and 29 controls. Decreased integrity of the CC was understood as increased mean diffusivity (MD) and/or decreased fractional anisotropy (FA) in diffusion tensor imaging. Peripheral IL-6 concentrations were measured in serum samples and IL-6 promoter methylation status of 6 CpG sites was analyzed in peripheral leukocytes by pyrosequencing., Results: Moderate positive correlations were found between CpG1 methylation and the MD of proximal regions of the CC (CCR1-CCR3) and between CpG mean and MD of CCR1 in SCH. Weaker positive correlations were found for CpG mean with CCR2 and CCR3 and negative correlations were found for CpG1 and FA of CCR3 in SCH. Multivariate regression showed that methylation of CpG1, type of antipsychotic treatment, and their interaction were significant independent predictors of MD of CCR1 in SCH. Methylation of CpG2 was negatively correlated with serum IL-6 in SCH., Conclusions: The methylation level of the IL-6 promotor region in peripheral leukocytes is associated with the integrity of the CC in schizophrenia and this association may depend on the type of antipsychotic treatment. Further studies are necessary to explain the mechanisms of the observed associations., Competing Interests: Declaration of competing interest The authors of submitted manuscript entitled: Higher methylation of IL-6 promoter region is associated with decreased integrity of corpus callosum in schizophrenia declare that they do not have any competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The experience sampling method (ESM) is a structured diary technique, which is used to assess thoughts, mood and appraise subjective experiences in daily life. It has been recognized as a useful tool for understanding the characteristics, dynamics, and underlying mechanisms of prodromal symptoms of psychosis. The present systematic review aimed to provide a qualitative synthesis of findings provided by the ESM studies conducted in people with psychosis risk states. A systematic review of the MEDLINE, ERIC, Academic Search Ultimate, and Health Source: Nursing/Academic Edition databases, utilizing search terms related to the ESM and the risk of psychosis was conducted. Out of 1069 publication records identified, 77 studies met the inclusion criteria for the review. Data were synthesized around the following topics: 1) assessment of symptoms dynamics and social functioning; 2) assessment of the mechanisms contributing to the emergence of psychotic experiences and 3) assessment of stress sensitivity. The studies have shown that negative emotions are associated with subsequent development of paranoia. The tendency to draw hasty conclusions, aberrant salience, self-esteem, and emotion regulation were the most frequently reported mechanisms associated with the emergence of psychotic experiences. Studies using the ESM also provided evidence for the role of stress sensitivity, in the development of psychotic symptoms. The ESM has widely been applied to studies investigating psychosis risk states, using a variety of protocols. Findings from this systematic review might inform future studies and indicate potential targets for interventions., Competing Interests: Declaration of Competing interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: There is conflicting evidence on impulsivity and its potential relationship with inhibitory control in schizophrenia. This study therefore aimed to identify differences in impulsivity and cognitive and motor inhibition between patients with deficit (DS) and non-deficit (NDS) schizophrenia and healthy controls (HC). We also explored the relationships between impulsivity and different dimensions of inhibitory control in all studied groups., Methods: The sample comprised 28 DS patients, 45 NDS patients, and 39 age-matched HC. A neuropsychological battery was used., Results: DS patients scored lower in venturesomeness, while those with NDS scored higher in impulsiveness compared to HC. In addition, both groups of patients scored higher on measures of cognitive and motor inhibition, including those relatively independent of information processing speed (although the results were slightly different after adjusting for IQ and/or years of education). Correlations between impulsivity and cognitive inhibition emerged in DS patients, while links between impulsivity and motor inhibition were observed in HC., Conclusions: Our results suggest the presence of deficits in experimentally assessed inhibitory control in schizophrenia patients, with predominant impulsivity in the NDS population. In addition, impulsivity may affect the cognitive control of inhibition in deficit schizophrenia. Nevertheless, due to the preliminary nature of these findings, they require further empirical verification in future research., (© 2024. The Author(s).)

We aimed to investigate as to whether psychotic-like experiences (PLEs) predict the perceived intent to seek treatment. Our secondary aim was to explore which PLEs predict the perceived need to seek treatment using a network analysis. The study was based on a community sample of individuals with a negative history of psychiatric treatment. At baseline, they completed questionnaires recording the presence of PLEs, depressive, and anxiety symptoms. After 6-7 months, they were reassessed with respect to the perceived intent to seek treatment. A total of 1100 individuals were assessed at baseline (aged 27.1 ± 5.1 years, 48.6 % males). The follow-up assessment was completed by 581 individuals (52.8 %). Higher baseline levels of PLEs were associated with a greater intent to seek treatment at the follow-up before (Beta = 0.289, p < 0.001) and after adjustment for sociodemographic characteristics, depressive and anxiety symptoms (Beta = 0.128, p = 0.004). A network analysis demonstrated that the intent to seek treatment was connected to five nodes of PLEs including "déjà vu experiences" (weight = 0.046), "problems in differentiating reality and imagination" (weight = 0.103), "a lack of control over own ideas or thoughts" (weight = 0.077), "being distracted by distant sounds" (weight = 0.105), and "paranoid thoughts" (weight = 0.145). Findings from the present study indicate that PLEs might contribute to help-seeking behaviors regardless of co-occurring depressive and anxiety symptoms. However, specific PLEs may differ with respect to their effects on the perceived intent to seek treatment., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Previous research has shown that moral judgments are affected by social cognitive abilities, such as theory of mind (ToM). This study examines how information about an actor's beliefs and the consequences of their actions affect the moral evaluation of the character's behavior in social events. Our research builds upon previous studies, which have shown that these factors contribute differently to moral judgments made by both adults and young children., Objectives: This study aimed to explore how participants with schizophrenia and healthy controls read stories about social situations in the context of moral judgments., Material and Methods: The study used the research procedure that included 4 variants of 16 scenarios describing social situations, and thus comprising 64 stories. After each story, participants evaluated their confidence level on a 4-point scale. To assess delusional beliefs, the Polish adaptation of the Peters Delusion Inventory (PDI) questionnaire and the Paranoia Checklist (PCh) were used. Respondents completed these questionnaires after completing the scenario test procedure., Results: In social situations, patients with paranoid schizophrenia were found to evaluate actions of protagonists who attempted to harm another person more leniently than when it was an accident. Conversely, healthy individuals judged those actors who expressed intentions to hurt another person significantly more harshly than in an accident situation. Metacognition measures show that paranoid schizophrenia patients make moral judgments with high confidence, despite being based on an incorrect reading of the other person's intentions., Conclusions: The study indicates that ToM has a significant impact on the moral judgment of others. Decreased moral cognition can result from both positive and negative symptoms. Deficits related to metacognition can also sustain such cognitive distortions.

The present study had the following aims: 1) to compare gut microbiota composition in patients with schizophrenia and controls and 2) to investigate the association of differentially abundant bacterial taxa with markers of inflammation, intestinal permeability, lipid metabolism, and glucose homeostasis as well as clinical manifestation. A total of 115 patients with schizophrenia during remission of positive and disorganization symptoms, and 119 controls were enrolled. Altogether, 32 peripheral blood markers were assessed. A higher abundance of Eisenbergiella, Family XIII AD3011 group, Eggerthella, Hungatella, Lactobacillus, Olsenella, Coprobacillus, Methanobrevibacter, Ligilactobacillus, Eubacterium fissicatena group, and Clostridium innocuum group in patients with schizophrenia was found. The abundance of Paraprevotella and Bacteroides was decreased in patients with schizophrenia. Differentially abundant genera were associated with altered levels of immune-inflammatory markers, zonulin, lipid profile components, and insulin resistance. Moreover, several correlations of differentially abundant genera with cognitive impairment, higher severity of negative symptoms, and worse social functioning were observed. The association of Methanobrevibacter abundance with the level of negative symptoms, cognition, and social functioning appeared to be mediated by the levels of interleukin-6 and RANTES. In turn, the association of Hungatella with the performance of attention was mediated by the levels of zonulin. The findings indicate that compositional alterations of gut microbiota observed in patients with schizophrenia correspond with clinical manifestation, intestinal permeability, subclinical inflammation, lipid profile alterations, and impaired glucose homeostasis. Subclinical inflammation and impaired gut permeability might mediate the association of gut microbiota alterations with psychopathological symptoms and cognitive impairment., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Psychotic-like experiences (PLEs) have been associated with poor sleep quality and increased suicide risk. However, the association between PLEs, insomnia and suicide risk has not been thoroughly investigated in prior studies. In this study, we aimed to explore as to whether insomnia moderates the association between PLEs and suicidal ideation. The study was performed in 4203 young adults (aged 18-35 years, 63.8% females). Data were collected using self-reports. Moderation analysis demonstrated that PLEs are associated with higher levels of the current suicidal ideation only in participants with greater severity of insomnia (B = 0.003, p < 0.001). This analysis included age, gender, education, occupation and depressive symptoms as covariates. Moreover, the network analysis demonstrated that nodes representing PLEs are connected to the node of current suicidal ideation only in participants with greater severity of insomnia. The nodes of PLEs connected to the current suicidal ideation node captured PLEs representing deja vu experiences, auditory hallucination-like experiences and paranoia (edge weights between 0.011 and 0.083). Furthermore, nodes representing PLEs were the three most central nodes in the network analysis of individuals with higher levels of insomnia (strength centrality between 0.96 and 1.10). In turn, the three most central nodes were represented by depressive symptoms in the network analysis of individuals with lower levels of insomnia (strength centrality between 0.67 and 0.79). Findings from this study indicate that insomnia might be an important risk factor of suicide in people with PLEs, especially those reporting deja vu experiences, auditory hallucination-like experiences and paranoia., (© 2023. The Author(s).)

Background: The intricate correlation between environmental exposures and mental health outcomes is increasingly acknowledged in psychiatric research. This study investigated the relationship between cumulative environmental risk factors, as represented by the exposome score (ES), and various domains of psychopathology within a non-clinical sample using a network analysis., Methods: We recruited 1100 participants (aged 18-35 years, 51.4% females) via a computer-assisted web interview, assessing psychopathological symptoms using standardized questionnaires. Environmental exposures, including season of birth, obstetric complications, advanced paternal age, childhood trauma, cannabis use, and urban upbringing, were self-reported to calculate the ES., Results: A network analysis revealed significant associations of the ES with psychotic-like experiences (PLEs) (weight = 0.113), manic (weight = 0.072), and attention-deficit/hyperactivity disorder symptoms (weight = 0.062). These connections did not differ significantly with respect to their weights. Depressive symptoms had the highest centrality and predictability. The mean predictability across all nodes included in the network was 0.344., Conclusions: These findings underscore the transdiagnostic nature of environmental exposures, aligning with previous research indicating broad associations between the ES and various facets of psychopathology. Our results suggest that the ES may not specifically correlate with PLEs but may indicate the risk of a broader psychopathology.

Previous studies investigating cortisol levels in people with depression or depressive symptoms have provided mixed findings. It has been suggested that the difficulty to generalize findings across studies in this field might be related to interindividual variability in experiencing depressive symptoms in terms of clinical and social contexts. Therefore, in the present study we aimed to test the association of morning cortisol levels and depressive symptoms in a non-clinical sample of young men taking into consideration the level of perceived loneliness. We hypothesized that the level of loneliness might moderate the association between morning cortisol levels and depressive symptoms. A total of 102 participants (aged 29.9 ± 5.0 years) completed questionnaires measuring the levels of depressive and anxiety symptoms, perceived stress, and loneliness. Cortisol levels were determined in four morning samples of saliva. There were significant positive correlations of the cortisol awakening response (CAR) and the mean increase in cortisol levels during the measurement period (MnInc) with the levels of depressive symptoms and loneliness. Moreover, a significant association of the depressive symptoms by loneliness interaction with the CAR and the MnInc was found. Specifically, the correlation of depressive symptoms with the CAR and the MnInc appeared to be significant and negative at high levels of loneliness. No significant association between depressive symptoms and the CAR was observed in men with low levels of loneliness. There were no significant associations of depressive symptoms, loneliness and the depressive symptoms by loneliness interaction with cortisol levels at awakening. In conclusion, findings from the present study indicate the importance of social contexts in understanding the association between altered activity of the hypothalamic-pituitary-adrenal axis and depressive symptoms in men., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Several studies have reported that psychotic-like experiences are associated with low levels of resilience and increased suicide risk. However, it remains unknown as to whether resilience mediates or moderates the association between psychotic-like experiences and suicide risk. Therefore, in this study, we aimed to explore the moderating and mediating effect of resilience in the association between psychotic-like experiences and suicide risk., Methods: A total of 1100 non-clinical, young adults (aged 18 - 35 years) with a negative history of psychiatric treatment were enrolled. Participants were recruited by the snowball sampling methodology through advertisements posted in the online platform. They were followed-up for about 7 months. Variables of interest were recorded using self-reports. Psychopathological assessment was conducted using the Prodromal Questionnaire-16, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Traumatic Experience Checklist, the Childhood Experience of Care and Abuse Questionnaire, the Cannabis Problems Questionnaire, the Connor-Davidson Resilience Scale-10, and the Mini-International Neuropsychiatric Interview. The STROBE statement guidelines were followed., Results: The moderation analysis revealed that higher levels of psychotic-like experiences and related distress at baseline were associated with significantly higher suicide risk at the follow-up after adjustment for baseline sociodemographic characteristics, depressive and anxiety symptoms, a history of childhood trauma, and problematic cannabis use. The interaction between follow-up resilience and distress related to baseline psychotic-like experiences was significantly and negatively associated with suicide risk at the follow-up. Specifically, the correlation between the level of distress related to psychotic-like experiences and suicide risk was significant and positive only in participants with lower levels of resilience. This interaction did not reach statistical significance for the baseline level of psychotic-like experiences. No significant mediating effect of the follow-up resilience level in the association between baseline psychotic-like experiences and the follow-up suicide risk was found., Conclusions: Findings from the present study indicate that resilience might protect against suicide risk in people with psychotic-like experiences. These findings could be applied in the formulation of early intervention strategies aimed at mitigating the risk of suicide. Future studies need to explore the effects of interventions targeting resilience for individuals with psychotic-like experiences., (© 2024. The Author(s).)

It has been reported that cumulative measures of risk factors for psychosis might help to predict its development. However, it remains unknown as to whether these measures are also associated with the extended psychosis phenotype that refers to a continuum of features bridging subclinical symptoms with clinically relevant outcomes. In this study, we aimed to investigate the association of the exposome score (ES) with psychosis risk in a non-clinical population. A total of 1100 non-clinical adults (aged 18-35 years, 51.4% females) with a negative history of psychiatric treatment were recruited. The Prodromal Questionnaire-16 (PQ-16) was used to screen for psychosis risk. Self-reports were used to record environmental exposures. The ES was significantly higher in participants with the positive PQ-16 screening. Specifically, the prevalence of obstetric complications, non-right handedness, all categories of childhood trauma, and problematic cannabis use was significantly higher in this group of participants. A network analysis demonstrated that the ES was directly connected not only to items representing psychotic experiences ("paranoid thoughts", "a lack of control over own ideas or thoughts", "thought echo", and "being distracted by distant sounds") but also those covering depressive or anxiety symptoms ("uninterested in things used to enjoy" and "feeling anxious when meeting people for the first time"). In conclusion, the ES is associated with the extended psychosis phenotype, suggesting its potential to identify individuals who may benefit from further psychosis risk assessment. The ES appears to contribute to non-specific psychopathology, which may, in some cases, progress to psychosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs)., Methods: A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled. Gut microbiota was analyzed using the 16 rRNA amplicon sequencing. Additionally, the levels of C-reactive protein (CRP), glucose and lipid metabolism markers were determined in the peripheral blood samples., Results: Altogether 14 genera showed differential abundance in patients with D-SCZ compared to ND-SCZ and HCs, including Candidatus Soleaferrea, Eubacterium, Fusobacterium, Lachnospiraceae UCG-002, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Libanicoccus, Limosilactobacillus, Mogibacterium, Peptococcus, Prevotella, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Slackia after adjustment for potential confounding factors. Observed alterations were significantly associated with cognitive performance in both groups of patients. Moreover, several significant correlations of differentially abundant genera with the levels of CRP, lipid profile parameters, glucose and insulin were found across all subgroups of participants., Conclusion: Findings from the present study indicate that individuals with D-SCZ show a distinct profile of gut microbiota alterations that is associated with cognitive performance, metabolic parameters and subclinical inflammation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest related to the subject of this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The role of anterior pituitary hormones - i.e., adrenocorticotropic hormone (ACTH), luteinizing and follicle stimulating hormones (LH and FSH), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) - in early schizophrenia and psychoses unclear. We thus performed a systematic review and meta-analysis on the blood concentrations of ACTH, LH and FSH, GH, PRL, and TSH in drug-naïve people with first-episode psychosis (FEP) as compared with healthy controls., Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed until September 2022. Data quality was appraised. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Between-study heterogeneity was estimated using the I 2 statistic. Sensitivity and meta-regression analyses were performed., Results: Twenty-six studies were included. Drug-naïve people with FEP, compared to healthy subjects, had higher blood concentrations of ACTH (k = 7; N = 548; SMD = 0.62; 95%CI: 0.29 to 0.94; p < 0.001; I 2 = 60.9%) and PRL (k = 17; N = 1757; SMD = 0.85; 95%CI: 0.56 to 1.14; p < 0.001; I 2 = 85.5%) as well as lower levels of TSH (k = 6; N = 677; SMD = -0.34; 95%CI: -0.54 to -0.14; p = 0.001; I 2 = 29.1%). Meta-regressions did not show any moderating effect of age (p = 0.78), sex (p = 0.21), or symptom severity (p = 0.87) on PRL concentrations in drug-naïve FEP. Available data were not sufficient to perform meta-analyses on FSH, LH, and GH., Conclusions: Drug-naïve people with FEP have altered ACTH, PRL, and TSH blood concentrations, supporting the hypothesis that an abnormal anterior pituitary hormone secretion may be involved in the onset of schizophrenia and psychoses. Further research is needed to elucidate the role of pituitary hormones in FEP., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Background: It has been shown that various aspects of clinical manifestation of schizophrenia are strongly related to social functioning. However, it remains unknown as to whether similar factors predict social functioning at various stages of psychosis. Therefore, the present study aimed to compare the effects of interconnections between various domains of psychopathology and neurocognition on social functioning in people during acute phase of psychosis and those during remission of positive and disorganization symptoms using a network analysis., Methods: Two independent samples of individuals with schizophrenia spectrum disorders were enrolled (89 inpatients during acute phase and 90 outpatients during remission of positive and disorganization symptoms). Clinical assessment covered the levels of functioning, positive, negative and depressive symptoms. Cognition was recorded using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Data were analyzed by means of the network analysis. Two separate networks of clinical symptoms, social functioning, and cognition (i.e., in patients during acute phase of psychosis and remitted outpatients with schizophrenia) were analyzed and compared with respect to the measures of centrality (betweenness, closeness, strength, and expected influence) and edge weights., Results: In both networks, the majority of centrality metrics (expected influence, strength, and closeness) had the highest values for the RBANS scores of attention (the sum of scores from two tasks, i.e., digit span and coding) and immediate memory. In both networks, social functioning was directly connected to positive, negative and depressive symptoms as well as the RBANS scores of attention and language. Additionally, in remitted patients, social functioning was directly connected to the RBANS score of immediate memory., Conclusions: Findings from the present study indicate the central role of cognitive deficits, especially those related to attention, processing speed, working and immediate memory in shaping functional impairments regardless of schizophrenia phase. Therapeutic interventions that aim to improve functional capacity need to target these domains of neurocognitive performance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Psychotic-like experiences (PLEs) are increasingly being recognized as subclinical phenomena that might predict the development of various mental disorders that are not limited to the psychosis spectrum. Accumulating evidence suggests that attention-deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) are highly comorbid mental disorders. However, their interactive effect on the occurrence of PLEs has not been investigated so far. Therefore, in the present study we aimed to investigate the effect of interaction between ADHD and PTSD symptoms on the level of psychotic-like experiences (PLEs) in the non-clinical sample., Methods: The study included 3,000 individuals aged 18-35 years with a negative history of psychiatric treatment. The symptoms of ADHD and PTSD were assessed using self-reports., Results: There was a significant association of the interaction between ADHD and PTSD with the level of reporting PLEs. This association remained significant after adjustment for age, gender, the level of education, the current vocational situation, lifetime history of problematic substance use, and depressive symptoms. Post-hoc tests demonstrated significantly higher levels of reporting PLEs in participants with positive screening for both ADHD and PTSD compared to other subgroups of participants. Also, individuals with positive screening for one vulnerability (either ADHD or PTSD) reported significantly higher levels of reporting PLEs compared to those with a negative screening for ADHD and PTSD. In turn, no significant differences between individuals reporting one vulnerability, i.e., between those with positive screening for ADHD and those with positive screening for PTSD, were observed., Conclusion: Findings from the present study imply that both PTSD and ADHD symptoms the interaction effect on the level of reporting PLEs that might be of importance for early intervention strategies. However, observed associations require replication in clinical samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gelner, Karska, Gawęda, Samochowiec and Misiak.)

It has been shown that narcissistic grandiosity and psychotic-like experiences (PLEs) may share the common psychological mechanisms, including impairments of metacognition, social cognition, cognitive biases, emotion regulation through fantasizing and dissociation. However, it remains unknown as to whether these mechanisms are associated with the occurrence of PLEs in people with narcissistic grandiosity. Therefore, in the present study, we approached a network analysis in order to investigate pathways from narcissistic grandiosity to PLEs taking into consideration the mediating effect of common psychological mechanisms. The study was based on a non-clinical sample of 1647 individuals, aged 18-35 years. Data were collected through self-reports administered in the online survey. There were no direct connections between narcissistic grandiosity and PLEs. However, four pathways connecting narcissistic grandiosity and PLEs through the effect of one mediating psychological mechanism were identified. These mechanisms covered external attribution biases, the need to control thoughts, social cognition, and emotion regulation through fantasizing. Among them, the shortest pathway led through the effects of external attribution biases. Age, gender, education and lifetime history of psychiatric treatment were included as covariates in a network analysis. Findings from this study indicate that higher levels of external attributions, the need to control thoughts, impairments of social cognition, and emotion regulation strategies based on fantasizing might be associated with the development of PLEs in people showing narcissistic grandiosity. These observations indicate potential targets for therapeutic approaches that aim to reduce the risk of developing comorbid psychopathology in people with grandiose narcissism traits., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Several studies have reported the association of psychotic-like experiences (PLEs) with non-suicidal self-injury (NSSI). It has been hypothesized that both constructs might share overlapping backgrounds. This study aimed to investigate the relationships between childhood trauma, depression, PLEs and lifetime characteristics of NSSI., Methods: Participants included individuals aged 18-35 years who had a negative history of psychiatric treatment. They were surveyed through the computer-assisted web interview. A network analysis was performed., Results: A total of 4203 non-clinical adults (63.8 % females) were enrolled. The characteristics of NSSI and a history of childhood sexual abuse were the most central nodes in the network. A history of childhood sexual abuse was the only category of childhood trauma that was directly connected to the characteristics of NSSI (i.e., longer lifetime duration of NSSI). The shortest pathways from other categories of childhood trauma (emotional abuse, emotional neglect and bullying) were connected to the lifetime characteristics through the effects of sexual abuse. However, other pathways were also possible and converged on nodes representing persecutory thoughts, déjàvu experiences, psychomotor retardation/agitation and suicidal ideation. These psychopathological symptoms were the only nodes directly connected to the characteristics of NSSI (i.e., lifetime duration and a history of severe NSSI)., Limitations: The main limitations include the use of a non-clinical sample and cross-sectional design., Conclusions: Our findings do not support the hypothesis that PLEs and NSSI might be associated due to shared correlates. In other words, the associations of childhood trauma and PLEs with NSSI might be independent., Competing Interests: Declaration of competing interest The authors declare no conflict of interest related to the subject of this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Schizophrenia is a multi-systemic disorder that is associated with lipid profile disturbances, altered glucose homeostasis and subclinical inflammation. It has been proposed that dysfunction of the gut-brain axis might underlie these alterations. Short-chain fatty acids (SCFAs) are considered to play a pivotal role in the gut-brain axis. In this study, we aimed to compare fecal levels of SCFAs in patients with schizophrenia and healthy controls (HCs), taking into consideration their relationship with common peripheral blood alterations observed in schizophrenia. The study included 100 stable outpatients with schizophrenia and 55 HCs. The levels of SCFAs (acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and lactic acid) in fecal samples were measured. Also, lipid profile together with the levels of C-reactive protein, glucose and insulin were determined. The levels of isovaleric acid were significantly higher in patients with schizophrenia after co-varying for age, sex, and the adherence to the Mediterranean diet. Moreover, there were significant positive correlations of the levels of valeric acid, isovaleric acid and CRP in patients with schizophrenia. In this group of participants, higher levels of isovaleric acid were associated with significantly lower scores of delayed memory after adjustment for potential covariates and interactions with CRP levels. Our results indicate that individuals with schizophrenia show altered levels of isovaleric acid that might be associated with impairments of delayed memory. The association with cognitive impairments might be independent of interactions with immune-inflammatory processes. Longitudinal and experimental studies are needed to test causal mechanisms of observed correlations., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Specific mechanisms underlying gut microbiota alterations in schizophrenia remain unknown. We aimed to compare gut microbiota between patients with schizophrenia and controls, taking into consideration exposure stress across lifespan, dietary habits, metabolic parameters and clinical manifestation. A total of 142 participants, including 89 patients with schizophrenia and 52 controls, were recruited. Gut microbiota were analyzed using the 16 S rRNA sequencing. Additionally, biochemical parameters related to glucose homeostasis, lipid profile and inflammation were assessed. Increased abundance of Lactobacillus and Limosilactobacillus as well as decreased abundance of Faecalibacterium and Paraprevotella were found in patients with schizophrenia. The machine learning analysis demonstrated that between-group differences in gut microbiota were associated with psychosocial stress (a history of childhood trauma, greater cumulative exposure to stress across lifespan and higher level of perceived stress), poor nutrition (lower consumption of vegetables and fish products), lipid profile alterations (lower levels of high-density lipoproteins) and cognitive impairment (worse performance of attention). Our findings indicate that gut microbiota alterations in patients with schizophrenia, including increased abundance of lactic acid bacteria (Lactobacillus and Limosilactobacillus) and decreased abundance of bacteria producing short-chain fatty acids (Faecalibacterium and Paraprevotella) might be associated with exposure to stress, poor dietary habits, lipid profile alterations and cognitive impairment., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.

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.

The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic in 2020 caused a rapid worsening of global mental health. Patients with severe mental disorders, including schizophrenia, are at higher risk of being infected. The neuroinvasive potential of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed. The aim of this article was to present a narrative and comprehensive review of multidimensional associations between schizophrenia and COVID-19 with special emphasis on common biological pathways. Online searches were performed in the PubMed database and covered the publication period until September 17, 2022. Search terms included "psychosis", "schizophrenia", "inflammation" and "COVID-19". Viewed as a neuroinflammatory state, schizophrenia shares several neurobiological mechanisms with the COVID-19. Environmental stress, common comorbidities of schizophrenia and adverse effects of antipsychotic treatment are associated with the higher severity and mortality of the COVID-19. Additionally, more frequent relapses of psychosis have been observed, and might be related to lower treatment adherence. In the context of clinical manifestation, higher level of negative symptoms has been identified among patients with schizophrenia during the pandemic. Improvements in mental health care policy and treatment adjustment are necessary to protect people with schizophrenia who are the population that is particularly vulnerable to the consequences of the COVID-19 pandemic. Future research will show if prenatal infection with the SARS-CoV-2 increases a risk of psychosis., (Copyright © 2023 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.)

There is evidence that subclinical inflammation and increased gut permeability might be involved in the pathophysiology of schizophrenia. Less is known about these phenomena in patients with the deficit subtype of schizophrenia (D-SCZ) characterized by primary and enduring negative symptoms. Therefore, in the present study we aimed to compare the levels of zonulin (the marker of gut permeability) and immune-inflammatory markers in patients with D-SCZ, those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). A total of 119 outpatients with schizophrenia and 120 HCs were enrolled. The levels of 26 immune-inflammatory markers and zonulin were determined in serum samples. The following between-group differences were significant after adjustment for multiple testing and the effects of potential confounding factors: 1) higher levels of interleukin(IL)- 1β and C-reactive protein (CRP) in patients with D-SCZ compared to those with ND-SCZ and HCs; 2) higher levels of tumor necrosis factor-α and RANTES in both groups of patients with schizophrenia compared to HCs and 3) higher levels of IL-17 in patients with D-SCZ compared to HCs. No significant between-group differences in zonulin levels were found. Higher levels of IL-1β and CRP were associated with worse performance of attention after adjustment for age, education and chlorpromazine equivalents. Also, higher levels of IL-1β were correlated with greater severity of negative symptoms after adjustment for potential confounding factors. In conclusion, individuals with D-SCZ are more likely to show subclinical inflammation. However, findings from the present study do not support the hypothesis that this phenomenon is secondary to increased gut permeability., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Depression is considered one of the most prevalent and burdensome mental disorders. Only 50-60% of patients respond to first-line treatment. Individuals with depression might benefit from personalized treatment, tailored to the individual needs of the patient. In this study, we aimed to explore the baseline characteristics of depressive symptoms associated with a good response to duloxetine treatment using a network analysis. Additionally, the relationship between baseline psychopathological symptoms and treatment tolerability was assessed., Methods: The sample of 88 drug-free patients with active depressive episode, who started monotherapy with increasing doses of duloxetine were evaluated. The Hamilton Depression Rating Scale (HAM-D) was used to assess depression severity and the UKU side effect rating scale to monitor adverse drug reactions (ADRs). A network analysis that explored interactions of specific baseline depression symptoms, treatment efficacy and tolerability was performed., Results: The node representing duloxetine treatment efficacy was directly connected to the nodes representing the first HAM-D item ("depressed mood") (edge weight = 0.191) and duloxetine dose (edge weight = 0.144). The node representing ADRs was directly connected to only one node representing the baseline score of the HAM-D anxiety (psychic) item (edge weight = 0.263)., Discussion: Our findings indicate that individuals with depression presenting greater levels of depressed mood and lower levels of anxiety symptoms might better respond to the treatment with duloxetine in terms of efficacy and tolerability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maciaszek, Pawłowski, Hadryś and Misiak.)

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.

Psychotic disorders often develop as the continuum of subclinical symptoms that include hallucination-like and delusion-like experiences, and are commonly referred to as psychotic-like experiences (PLEs). To date, a number of neurodevelopmental risk factors of psychosis have been detected, yet their mutual interplay remains unknown. Therefore, we aimed to investigate the additive association of childhood trauma history, reading disabilities and symptoms of attention-deficit/hyperactivity disorder (ADHD) with psychosis proneness. A total of 3000 young adults (58.3% females, aged 18-35 years) with a negative history of psychiatric treatment were recruited to the cross-sectional study through computer-assisted web interview. Self-reports were administered to measure childhood trauma history, ADHD symptoms and reading disabilities. Linear regression analyses revealed significant main associations of childhood trauma history and reading disabilities with higher levels of PLEs. There were no significant main associations of ADHD with the level of PLEs. However, the associations of all possible interactions between neurodevelopmental risk factors with the level of PLEs were significant. Our findings suggest that childhood trauma history and reading disabilities may additively increase a risk of psychosis. The present findings bring new implications for early intervention strategies in psychosis and posit the rationale of recording the accumulation of neurodevelopmental vulnerabilities in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Schizophrenia is a neurodevelopmental disorder with genetic and environmental factors involved in its aetiology. Genetic liability contributing to the development of schizophrenia is a subject of extensive research activity, as reliable data regarding its aetiology would enable the improvement of its therapy and the development of new methods of treatment. A multitude of studies in this field focus on genetic variants, such as copy number variations (CNVs) or single-nucleotide variants (SNVs). Certain genetic disorders caused by CNVs including 22q11.2 microdeletion syndrome, Burnside-Butler syndrome (15q11.2 BP1-BP2 microdeletion) or 1q21.1 microduplication/microdeletion syndrome are associated with a higher risk of developing schizophrenia. In this article, we provide a unifying framework linking these CNVs and their associated genetic disorders with schizophrenia and its various neural and behavioural abnormalities., (© 2022. The Author(s).)

This study compared cognitive domains between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), analyzing relationships between psychopathological dimensions and cognitive domains. A total of 29 DS patients, 45 NDS patients, and 39 HC subjects participated. Cognitive domains were measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale. Clinical groups performed poorer than HC groups in regards to speed of processing, attention/vigilance, working memory, verbal and visual learning and memory, reasoning and problem solving, and social cognition. DS patients scored poorer than NDS patients in terms of all cognitive domains and the overall score, except for reasoning and problem solving. Positive, negative, disorganization, and resistance symptoms were related to cognitive functions only in NDS patients. Our findings suggest that the MCCB battery is sensitive to detecting cognitive dysfunctions in both deficit and non-deficit schizophrenia., Competing Interests: The authors declare no conflict of interest.

This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits.

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.

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.

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH 4 ), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs)., Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I 2 statistic., Results: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I 2  = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I 2  = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH 4 ., Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Psychometric properties of the Self-evaluation of Negative Symptoms (SNS) in subjects with the deficit subtype of schizophrenia (SCZ-D) have not been investigated so far. This study had the following aims: (1) to assess psychometric properties of SNS in subjects with SCZ-D and (2) to explore the usefulness of SNS, in comparison with other clinical characteristics, in screening for SCZ-D., Methods: Participants were 82 stable outpatients with schizophrenia, including 40 individuals with SCZ-D and 42 individuals with the non-deficit subtype (SCZ-ND)., Results: Internal consistency was acceptable-to-good in both groups. Factor analysis revealed two dimensions (apathy and emotional). There were significant positive correlations of the SNS total score with the subscore of negative symptoms from the Positive and Negative Syndrome Scale (PANSS) and significant negative correlations with scores of the Social and Occupational Functioning Assessment Scale (SOFAS) in both groups, indicating good convergent validity. The following measures were found to be appropriate screening tools for differentiating SCZ-D and SCZ-ND (p < 0.001): the SNS total score (area under the curve [AUC]: 0.849, cut-off ≥16, sensitivity: 80.0%, specificity: 78.6%), the PANSS subscore of negative symptoms (AUC: 0.868, cut-off ≥11, sensitivity: 90.0%, specificity: 78.6%), and the SOFAS (AUC: 0.779, cut-off ≤59, sensitivity: 69.2%, specificity: 82.5%). Also, adding the SOFAS (cut-off ≤59) to the SNS (cut-off: ≥16) further improved sensitivity and specificity (AUC: 0.898, p < 0.001, sensitivity = 87.5%, specificity = 82.2%). Cognitive performance and age of psychosis onset were not found to be suitable measures for differentiating SCZ-D and SCZ-ND., Conclusion: The present findings indicate that the SNS has good psychometric properties in subjects with SCZ-D and those with SCZ-ND. Moreover, the SNS, the PANSS, and the SOFAS might be used as screening tools for SCZ-D., (© 2023 S. Karger AG, Basel.)

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.