Greater methylation of the IL-6 promoter region is associated with decreased integrity of the corpus callosum in schizophrenia.

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 CpGmean and MD of CCR1 in SCH. Weaker positive correlations were found for CpGmean 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.

The experience sampling methodology in psychosis risk states: A systematic review.

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.

Coping styles do not interact with the association between childhood trauma history and the immune-inflammatory phenotype of schizophrenia: Findings from a cross-sectional study.

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.

Blindness of intentions and metacognitive deficits during moral judgements in schizophrenia.

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 Associations of Exposome Score with Various Domains of Psychopathology: A Network Analysis in a Non-Clinical Sample.

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.

Psychotic-like experiences predict the perceived intent to seek treatment: A network perspective.

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.

Resilience buffers the association between psychotic-like experiences and suicide risk: a prospective study from a non-clinical sample.

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.

Associations of gut microbiota alterations with clinical, metabolic, and immune-inflammatory characteristics of chronic schizophrenia.

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.

Modelling the effects of the exposome score within the extended psychosis phenotype.

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.

The association between depression and the cortisol awakening response is moderated by loneliness in men from a non-clinical sample.

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.

Insomnia moderates the association between psychotic-like experiences and suicidal ideation in a non-clinical population: a network analysis.

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.

Ethical dilemmas in contemporary psychiatry: Findings from a survey of National Psychiatric Associations in Europe.

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.

Blood concentrations of anterior pituitary hormones in drug-naïve people with first-episode psychosis: A systematic review and meta-analysis.

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 I2 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; I2 = 60.9%) and PRL (k = 17; N = 1757; SMD = 0.85; 95%CI: 0.56 to 1.14; p < 0.001; I2 = 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; I2 = 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.

Effects of the interaction between PTSD and ADHD symptoms on the level of reporting psychotic-like experiences: findings from a non-clinical population.

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.

Assessment of interrelationships between cognitive performance, symptomatic manifestation and social functioning in the acute and clinical stability phase of schizophrenia: insights from a network analysis.

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.

The Impact of the CYP2D6 and CYP1A2 Gene Polymorphisms on Response to Duloxetine in Patients with Major Depression.

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.

Understanding pathways from narcissistic grandiosity to psychotic-like experiences: Insights from the network analysis.

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.

Altered levels of fecal short-chain fatty acids are associated with subclinical inflammation and worse cognitive performance in patients with schizophrenia.

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.

Schizophrenia and the COVID-19 pandemic: A narrative review from the biomedical perspective.

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.