Search Results (62)

Supplementation with probiotics seems to confer protective effects in individuals with schizophrenia (SZ), although available results are inconclusive. The aim of this study was to systematically review existing randomized clinical trials (RCTs) to critically assess the effect of probiotics on psychiatric symptoms, anthropometric indicators, lipid profiles, glycemic indices, inflammation, and oxidative stress in adults with SZ. A systematic search was conducted in four databases from inception until January 2025. Six RCTs were included in the quantitative analysis that demonstrated beneficial effects of probiotics on SZ severity determined via the Positive and Negative Syndrome Scale (PANSS), with significant reductions in PANSS (MD = −0.50, p = 0.001), PANSS Negative (MD = −0.31, p = 0.050), and PANSS General scores (MD = −0.33, p = 0.036), alongside reductions in body weight (MD = −0.92, p = 0.000), body mass index (MD = −0.53, p = 0.016), and total cholesterol (SMD = −0.34, p = 0.005). Furthermore, probiotic interventions reduced baseline glucose (SMD = −0.59, p = 0.000), insulin (MD = −0.68, p = 0.000), and measures of insulin sensitivity/resistance and significantly improved biomarkers of inflammation and oxidative stress. To summarize, this meta-analysis suggests that probiotics may confer beneficial effects in patients with SZ through improving psychiatric symptoms as well as markers of body weight, lipid and glucose metabolism, inflammation, and oxidative stress. Full article

Background/Objectives: We aimed to evaluate asprosin and peptide tyrosine–tyrosine (PYY) levels in schizophrenia patients and the relationships between these levels and clinical severity, as well as whether these two hormones have a role in determining the disease and/or the phases of the disease. Methods: This study included 50 patients with schizophrenia in the remission phase, 50 in the acute phase, and 50 controls. The Positive and Negative Syndrome Scale (PANSS) was filled out for patients. The patients’ biochemical parameters and asprosin and PYY levels were measured. Results: Levels of asprosin and PYY were significantly different in all three groups (p < 0.001, p < 0.001). In the remission phase group, asprosin levels had a negative effect on PANSS general symptomatology scores (p: 0.002, p < 0.001). In the acute phase group, while PYY levels showed a negative effect on PANSS general symptomatology scores (p: 0.031), asprosin levels had a negative effect on all subscales of PANSS (p < 0.001). In the acute phase, a one-unit decrease in asprosin levels was associated with a 93% increase in PANSS total scores. The results of the receiver operating characteristic (ROC) analysis to distinguish the acute phase showed that PYY could not be used for diagnosis (p: 0.066), but asprosin was associated with the acute phase of schizophrenia (p < 0.001) and both asprosin and PYY were associated with the disease (p < 0.001, p < 0.001). Conclusions: We think that both asprosin and PYY can be used as potential biomarkers to identify schizophrenia, and only asprosin to identify the phases of the disease. PYY and asprosin levels may be markers that can be used to determine clinical severity. Full article

Background/Objectives: Schizophrenia is a clinically heterogeneous complex disorder with a substantial polygenic basis. The discovery of phenotypes indexing genetic differences advances research into the schizophrenia etiology but has proven to be challenging. The study aimed to further clarify the relationships of schizophrenia polygenic risk scores (SZ-PRSs) with a comprehensive array of schizophrenia antecedents and presentations using a culturally and ethnically homogeneous sample of schizophrenia spectrum patients. Methods: The top and bottom deciles (n = 172) of the SZ-PRS distribution in a group of 861 patients were compared on information derived from medical records using logistic regression. Results: High SZ-PRSs were associated with female sex, family history of a wide range of neuropsychiatric conditions, moderately poor premorbid social and cognitive adjustment in childhood, the schizophrenia diagnosis, and positive and “abnormal” psychomotor symptoms. The low-SZ-PRS group demonstrated an accumulation of both individuals with milder forms of SZ spectrum disorders and those with severe premorbid abnormalities in the social, cognitive, and neurological domains. Conclusions: The results highlight moderately poor premorbid social and cognitive adjustment as characteristic manifestations of the polygenic component of the schizophrenia etiology and provide the first piece of PRS-based evidence for the long-standing idea of a higher liability threshold in women. The presence of milder and severe cases in the bottom SZ-PRS decile, suggesting its etiological heterogeneity, might be an important source of the inconsistency in the previous research on SZ-PRSs’ relationship with schizophrenia phenotypes and should be considered in future studies. Full article

Background and Objectives: Growing evidence suggested that abnormal lipid metabolism (ALM) was associated with an increased severity of depressive symptoms, but no previous studies have examined the differences in comorbid ALM in major depressive disorder (MDD) patients of different ages of onset. We aim to compare the differences in the prevalence and clinical correlates of ALM between early-onset and late-onset patients with first-episode and drug-naive (FEDN) MDD patients. Methods: Using a cross-sectional design, we recruited a total of 1718 FEDN MDD outpatients in this study. We used the 17-item Hamilton Rating Scale for Depression (HAMD-17), The Hamilton Anxiety Rating Scale (HAMA), the Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity Scale (CGI-S) to assess their depression, anxiety, and psychotic symptoms and clinical severity, respectively. Results: There were 349 patients (20.3%) in the early-onset subgroup and 1369 (79.7%) in the late-onset subgroup. In this study, 65.1% (1188/1718) of patients were diagnosed with ALM. The prevalence of ALM in the late-onset group (81.5%, 1116/1369) was significantly higher than that in the early-onset group (20.6%, 72/349) (p = 0.36, OR = 1.147, 95%CI = 0.855–1.537). The HAMD total score (OR = 1.34, 95% CI = 1.18–1.53, p < 0.001) was the only risk factor for ALM in early-onset MDD patients. In late-onset MDD patients, the HAMD total score (OR = 1.19, 95% CI = 1.11–1.28, p < 0.001), TSH (OR = 1.25, 95% CI = 1.16–1.36, p < 0.001), CGI (OR = 1.7, 95% CI = 1.31–2.19, p < 0.001), and anxiety (OR = 2.22, 95% CI = 1.23–4.02, p = 0.008) were risk factors for ALM. Conclusion and Scientific Significance: Our results suggest that there are significant differences in the prevalence and clinical factors of comorbid ALM between early-onset and late-onset FEND MDD patients. Full article

Schizophrenia is a complex and heterogenous psychiatric disorder characterized by positive, negative, and cognitive symptoms. Our previous study identified three subgroups of schizophrenia patients based on plasma microRNA (miRNA) profiles. The present study aims to (1) verify the reproducibility of the miRNA-based patient stratification and (2) explore the pathophysiological pathways linked to the symptoms using plasma miRNAs. We measured levels of 376 miRNAs in plasma samples of schizophrenia patients and obtained their Positive and Negative Syndrome Scale (PANSS) scores and the Brief Assessment of Cognition in Schizophrenia (BACS) scores. The plasma miRNA profiles identified similar subgroups of patients as in the previous study, suggesting miRNA-based patient stratification is potentially reproducible. Our multivariate analysis identified optimal combinations of miRNAs to estimate the PANSS positive and negative subscales and BACS composite scores. Those miRNAs consistently enriched ‘inflammation’ and ‘NFκB1′ according to miRNA set enrichment analysis. Our literature-based text mining and survey confirmed that those miRNAs were associated with IL-1β, IL-6, and TNFα, suggesting that exacerbated positive, negative, and cognitive symptoms are associated with high inflammation. In conclusion, miRNAs are a potential biomarker to identify patient subgroups reflecting pathophysiological conditions and to investigate symptom-related molecular mechanisms in schizophrenia. Full article

Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. Methods: The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). Results: Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 (p = 0.012), IL-12 (p = 0.049) and anti-inflammatory IL-10 (p = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. Conclusions: These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients. Full article

Background: Research on the interaction between antipsychotic treatment and cognitive dysfunction in schizophrenia spectrum disorders (SSDs) is extensive, yet the role of genetic polymorphisms in catechol-O-methyltransferase (COMT) and neuregulin 1 (NRG1) remains underexplored. Methods: This study evaluates the impact of COMT (rs4680) and NRG1 (rs3924999 and rs35753505) polymorphisms on cognitive functions in SSD patients. A cross-sectional study was conducted with fifty-four patients, assessed using the Positive and Negative Syndrome Scale (PANSS) and the CNS Vital Signs battery. Results: Significant cognitive function differences were observed across SSD diagnostic categories (p < 0.001). The NRG1 rs35753505 TT genotype was significantly associated with better verbal memory performance compared to the CC genotype (p = 0.03), while no significant differences were observed for other genotypes. The NRG1 rs3924999 AA genotype showed superior reasoning performance compared to AG and GG genotypes (p = 0.01), with AG and GG associated with lower scores (p = 0.01 and p = 0.02, respectively). Additionally, the COMT Val158Met genotype significantly influenced processing speed, with patients at the first episode of psychosis showing higher scores than chronic patients (p = 0.01). Conclusions: These findings suggest that NRG1 and COMT polymorphisms may influence cognitive domains in schizophrenia spectrum disorders, potentially informing personalized treatment and cognitive rehabilitation strategies. Full article

Schizophrenia poses significant challenges for individuals and caregivers, often leading to recurrent hospitalizations. Limited information on patients with schizophrenia and multiple hospitalizations in Romania is available in the scientific literature. Our study aimed to evaluate the characteristics of patients with schizophrenia with multiple hospitalizations in a single center in Cluj-Napoca, analyzing if specific patterns exist between patients with two or more hospitalizations or between men and women. We conducted a retrospective study on patients diagnosed with schizophrenia according to the 10th revision of the International Classification of Diseases (ICD 10), hospitalized at the County Emergency Hospital of Cluj-Napoca, Romania, between 2018 and 2022. Data on demographics, somatic comorbidities, symptom severity using the positive and negative syndrome scale (PANSS) or the brief psychiatric rating scale (BPRS), antipsychotic medication, and adverse effects were collected. We evaluated 62 patients, aged from 23 to 57 years, with 157 hospitalizations (ranging from two to seven per patient). No familial history of schizophrenia (56.5%) or bipolar disorder (71%) was reported by most patients. Forty-eight patients were male, and 45 had two hospitalizations. Age, sex, living place and conditions, season of birth, and marital status were similar in patients with two or more than two hospitalizations (p-values > 0.10). Significant differences were observed between patients with two or more than two hospitalizations regarding smoking (63.3% vs. 79.1%, p-value = 0.0029) and symptoms of fear at admission (40.0% vs. 65.7%, p-value = 0.0015). We observed lower scores in the overall PANSS and BPRS scores at discharge compared to admission (p-values < 0.001), regardless of the group (two or more than two hospitalizations, men vs. women). Men and women showed differences in hospitalization stays (median 17.25 vs. 15 days, p-value < 0.001) and BPRS scores at admission (p-value = 0.012) and discharge (p-value = 0.016). Fewer First-Generation Antipsychotics were prescribed for those with two admissions, and nearly half reported adverse effects, notably tachycardia (29%), with similar occurrence within groups. Our results showed that the candidate for multiple hospitalizations is a male, with a mean age of 37 years, unmarried, and living with someone in urban settings, more likely a smoker who exhibits fear symptoms. Full article

(1) Background: Schizophrenia is a chronic and progressive neuropsychiatric illness. Apart from positive and negative symptoms, 98% of the population diagnosed with schizophrenia have impaired cognitive functioning, which significantly influences the quality of life. The correlation between lipids and cognitive functioning has been well established. Our study aimed to investigate correlations between cognitive functions, the severity of schizophrenia symptoms, and lipid profiles. (2) Methods: Fifty-two women diagnosed with schizophrenia participated in this study. Cognitive functioning was measured using the Wisconsin Card Sorting Test (WCST). The Positive and Negative Symptom Scale (PANSS) was used. The serum lipid profile, including low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and triglycerides was measured. (3) Results: Better cognitive functions were associated with normal HDL levels, while low HDL levels correlated with worse WSCT scores. Only the PANSS negative subscale showed a correlation with HDL levels. Correlations with chronicity of schizophrenia and the patient’s age with poorer cognitive functions, but not with symptom severity, were detected. Early/late age at onset did not influence WSCT scores. (4) Conclusions: Our results suggest high HDL levels might be a protective factor against cognitive impairment. The influences of age and illness duration also play a vital role in cognitive performance. Full article

Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients. Full article

Pharmacogenetic markers are current targets for the personalized treatment of psychosis. Limited data exist on COMT and NRG1 polymorphisms in relation to risperidone treatment. This study focuses on the impact of COMT rs4680 and NRG1 (rs35753505, rs3924999) polymorphisms on risperidone treatment in schizophrenia spectrum disorders (SSDs). This study included 103 subjects with SSD treated with risperidone monotherapy. COMT rs4680, NRG1 rs35753505, and rs3924999 were analyzed by RT-PCR. Participants were evaluated via the Positive and Negative Syndrome Scale (PANSS) after six weeks. Socio-demographic and clinical characteristics were collected. COMT rs4680 genotypes significantly differed in PANSS N scores at admission: AG>AA genotypes (p = 0.03). After six weeks of risperidone, PANSS G improvement was AA>GG (p = 0.05). The PANSS total score was as follows: AA>AG (p = 0.04), AA>GG (p = 0.02). NRG1 rs35753504 genotypes significantly differed across educational levels, with CC>CT (p = 0.02), and regarding the number of episodes, TT>CC, CT>CC (p = 0.01). The PANSS total score after six weeks of treatment showed a better improvement for TT<CT genotypes (p = 0.01). NRG1 rs3924999 genotypes revealed GG<AG (p = 0.02) for PANSS G scores after six weeks, with AG and GG requiring higher doses (p = 0.007, p = 0.02). Overall, our study suggests that the genetic polymorphisms COMT rs4680, NRG1 rs35753505, and rs3924999 significantly impact the treatment response to risperidone in patients with SSD. Full article

Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes (p = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers. Full article

Background: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. Methods: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). Conclusions: This study provides initial evidence supporting brexpiprazole’s efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed. Full article

Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched ‘Immune Response’ according to miRNA set enrichment analysis and were reported to negatively regulate IL-1β, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched ‘Cytokine-cytokine receptor interaction’ according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia. Full article

Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = −2.341, p = 0.021). A safety analysis indicated lurasidone’s good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone’s efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population. Full article