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.

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.

Impulsivity and inhibitory control in deficit and non-deficit schizophrenia.

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.

Does social isolation predict the emergence of psychotic-like experiences? Results from the experience sampling method study.

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.

The Impact of Childhood Trauma on the Negative Symptoms of Schizophrenia.

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.

Appetite-regulating hormones in bipolar disorder: A systematic review and meta-analysis.

Impaired hormonal regulation of appetite may contribute to higher cardiovascular risk in bipolar disorder (BD). We performed a systematic review and meta-analysis of studies investigating peripheral blood levels of appetite-regulating hormones in BD and controls. A total of 32 studies were included. Leptin and insulin levels were significantly elevated in patients with BD during euthymia, but not in other mood states. Greater differences in the number of male participants between patients with BD and healthy controls were associated with higher effect size estimates for the levels of insulin. There were significant positive correlations of effect size estimates for the levels of adiponectin with the percentage of individuals with type I BD and duration of BD. Our findings point to the mechanisms underlying high rates of cardiometabolic comorbidities in BD. Moreover, they suggest that investigating hormonal regulation of appetite might help to understand differences in the neurobiology of BD types.

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.

Associations of neurodevelopmental risk factors with psychosis proneness: Findings from a non-clinical sample of young adults.

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.

The Self-Evaluation of Negative Symptoms in Differentiating Deficit Schizophrenia: The Comparison of Sensitivity and Specificity with Other Tools.

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.

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.

Gut microbiota alterations in stable outpatients with schizophrenia: findings from a case-control study.

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.

A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals.

Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25-0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: -0.42-1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = -0.40, 95 %CI: -0.68 - -0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism.

The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites.

Growing evidence suggests that a dysregulation of the kynurenine pathway (KP) occurs in bipolar disorder (BD). This systematic review and meta-analysis aimed at assessing the possible differences in peripheral blood levels of KP metabolites between individuals with BD and healthy controls. We searched Medline, Embase, and PsycInfo electronic databases for articles indexed up to February 2020. We included any observational study comparing the peripheral blood levels of at least one KP metabolite between adults with BD and healthy controls. Random-effects meta-analyses were carried out generating pooled standardized mean differences (SMDs). Heterogeneity between studies was estimated using the I2 index. Meta-regression and sensitivity analyses were conducted. Sixteen studies met inclusion criteria and were included in our study. Meta-analyses showed that individuals with BD have lower peripheral blood levels of tryptophan (SMD = -0.29), kynurenine (SMD = -0.28), kynurenic acid (SMD = -0.30), and xanthurenic acid (SMD = -0.55), along with lower kynurenic acid to kynurenine (SMD = -0.60) and kynurenic acid to quinolinic acid (SMD = -0.37) ratios, than healthy controls. Individuals with a manic episode showed the greatest reductions in tryptophan levels (SMD = -0.51), whereas kynurenic acid levels were more reduced among subjects in a depressive phase (SMD = -0.70). Meta-regression and sensitivity analyses confirmed our results. The findings of the present meta-analysis support the hypothesis of an abnormality of the KP in BD. Considering the partial inconsistency of the findings and the small-to-medium magnitude of the estimated effect sizes, additional research assessing possible mediators or confounders is needed.

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

Clinical Correlates of the NR3C1 Gene Methylation at Various Stages of Psychosis.

BACKGROUND: Dysregulation of epigenetic processes might account for alterations of the hypothalamic-pituitary-adrenal axis observed in patients with schizophrenia. Therefore, in this study, we aimed to investigate methylation of the glucocorticoid receptor (NR3C1) gene in patients with schizophrenia-spectrum disorders, individuals at familial high risk of schizophrenia (FHR-P), and healthy controls with respect to clinical manifestation and a history of psychosocial stressors. METHODS: We recruited 40 first-episode psychosis patients, 45 acutely relapsed schizophrenia (SCZ-AR) patients, 39 FHR-P individuals, and 56 healthy controls. The level of methylation at 9 CpG sites of the NR3C1 gene was determined using pyrosequencing. RESULTS: The level of NR3C1 methylation was significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients compared with other subgroups of participants. Individuals with FHR-P and healthy controls had similar levels of NR3C1 methylation. A history of adverse childhood experiences was associated with significantly lower NR3C1 methylation in all subgroups of participants. Higher methylation of the NR3C1 gene was related to worse performance of attention and immediate memory as well as lower level of general functioning in patients with psychosis. CONCLUSIONS: Patients with schizophrenia-spectrum disorders show altered levels of NR3C1 methylation that are significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients. Higher methylation of the NR3C1 gene might be related to cognitive impairment observed in this clinical population. The association between a history of adverse childhood experiences and lower NR3C1 methylation is not specific to patients with psychosis. Longitudinal studies are needed to establish causal mechanisms underlying these observations.

Assessment of the association between non-suicidal self-injury disorder and suicidal behaviour disorder in females with conduct disorder.

BACKGROUND: Non-suicidal self-injury (NSSI) and aggression have been demonstrated to serve as risk factors of suicidal behaviours (SB). Non-suicidal self-injury disorder (NSSID) and Suicidal Behaviour Disorder (SBD) are among new diagnostic categories for further studies in the DSM-5 classification. METHODS: We recruited 196 girls (aged 15.5 ± 1.2 years) diagnosed with conduct disorder (CD). All of them were assessed with respect of non-suicidal self-injury acts, suicidal attempts, psychopathology, self-esteem and general functioning. RESULTS: Age of NSSI onset was significantly lower compared to age of first suicidal attempt. SBD was present in 50.0% of patients with NSSID and the prevalence of NSSID in individuals with SBD was estimated at 52.2%. A diagnosis of NSSID, with at least 8 days of engagement in self-injuries during the preceding year, significantly predicted the risk of SBD. This effect appeared to be independent of depressive symptomatology. LIMITATIONS: Our results cannot be generalized over the whole population of individuals diagnosed with CD because of a lack of male patients, as well as individuals with the most severe and mildest forms of CD. Causal inferences cannot be established due to a cross-sectional study design. CONCLUSIONS: The NSSID with at least 8 days of engagement in self-injuries during the preceding year serves as a predictor of SBD independently of the effects of depressive symptoms. Longitudinal studies are required to confirm our findings.

A pro-inflammatory phenotype is associated with behavioural traits in children with Prader-Willi syndrome.

Several lines of evidence indicate that immune-inflammatory alterations are widely observed in various mental disorders. Genetic syndromes with high risk of psychiatric disorders may constitute a model for studies investigating this phenomenon. One of such genetically determined neurodevelopmental disorders is the Prader-Willi syndrome (PWS). Therefore, we aimed to profile a broad panel of immune-inflammatory markers in patients with PWS, taking into account co-morbid psychopathology. Participants were 20 children with PWS, and 20 healthy children matched for age, sex and body mass index. Behavioural symptoms and co-occurring psychopathological symptoms were assessed using the Child Behaviour Checklist (CBCL). We found significantly elevated levels of interleukin (IL)-1ß and IL-13 in patients with PWS. There were significant positive correlations between the levels of IL-1ß and scores of the following externalizing and internalizing CBCL domains: withdrawn/depressed, social problems, thought problems, attention problems, delinquent and aggressive behaviour in PWS children. Moreover, higher levels of IL-13 were associated with more severe psychopathology in terms of social and attention problems as well as delinquent and aggressive behaviour. Our findings imply that subclinical inflammation, observed as elevated IL-1ß and IL-13 levels, appears only in PWS patients and is correlated to several psychopathological symptoms.

Chemokine alterations in bipolar disorder: A systematic review and meta-analysis.

We aimed to perform a systematic review and meta-analysis of studies examining the levels of chemokines in peripheral blood of patients with bipolar disorder (BD) and healthy controls. Meta-analysis was based on random-effects models with Hedges' g as the effect size estimate. We included 13 eligible studies (1221 BD patients and 663 controls). The following chemokines were analysed: interleukin-8 (IL-8), monocyte-chemoattractant protein-1 (MCP-1), eotaxin-1, eotaxin-2 and interferon-γ-induced protein 10 (IP-10). The levels of IL-8 (N = 8, g = 0.26, 95%CI: 0.11-0.41, p < 0.001), MCP-1 (N = 8, g = 0.40, 95%CI: 0.18-0.63), eotaxin-1 (N = 3, g = 0.55, 95%CI: 0.21-0.89, p = 0.001) and IP-10 (N = 4, g = 0.95, 95%CI: 0.67-1.22, p < 0.001) were significantly higher in BD patients as compared with controls. Subgroup analyses revealed that elevated levels of IL-8 (N = 5, g = 0.75, 95%CI: 0.42-1.07, p < 0.001) and MCP-1 (N = 4, g = 0.57, 95%CI: 0.28-0.86, p < 0.001) appeared only in BD patients during their depressive phase. Illness duration was associated with significantly lower levels of IL-8 in meta-regression analysis. In turn, elevated levels of IP-10 were present during euthymia (N = 2, g = 0.76, 95%CI: 0.43-1.10, p < 0.001) but not depression (N = 2, g = 1.81, 95%CI: -0.16 to 3.77, p = 0.072). The analysis of eotaxin-1 levels was mainly based on studies of euthymic BD patients (N = 3). Our results suggest that chemokine alterations in BD might be related to mood state. Elevated levels of IL-8 and MCP-1 might be specific to depression. Available evidence indicates that increased levels of eotaxin-1 and IP-10 appear in euthymia; however, more studies are needed to address these alterations in other mood states.

Association between DRD2 and ANKK1 polymorphisms with the deficit syndrome in schizophrenia.

BACKGROUND: The clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia. METHODS: Three SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity. CONCLUSIONS: The results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.

Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study.

We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1ß, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients. These differences, except for the difference in eotaxin-1 levels, appeared to be significant after co-varying for the dosage of antipsychotics. There were no significant differences in the levels of immune markers between first-episode schizophrenia (FES) patients and controls. Our meta-analysis revealed elevated levels of MCP-1 in first-episode psychosis (FEP) patients and MES individuals. Other chemokine alterations (elevated levels of IL-8, eotaxin-1 and MIP-1ß) were present only in MES patients. Our results indicate that dysregulation of immune response in schizophrenia develops with illness progression or appears as a long-term medication effect. Chemokine alterations are another example of aberrant immune response in schizophrenia patients. Elevated levels of MCP-1 might represent trait markers since these alterations were found in FEP and MES patients. Other chemokine alterations might be the markers of disease progression or might represent medication effects.