Positive And Negative Syndrome Scale Negative Scores Research Articles

Pentoxifylline adjunct to risperidone for negative symptoms of stable schizophrenia: A randomized, double-blind, placebo-controlled trial

Abstract Background Negative symptoms of schizophrenia represent an unmet therapeutic need for many patients on whom pentoxifylline may be effective in terms of its dopaminergic, anti-inflammatory, and cerebral blood flow-increasing properties. This study aimed to evaluate pentoxifylline as a therapeutic agent for improving negative symptoms of schizophrenia. Methods Chronic schizophrenia outpatients experiencing significant negative symptoms were randomly allocated to receive pentoxifylline 400 mg or matched placebo q12hr for eight weeks. All patients were clinically stable as they had received risperidone for at least two months, which was continued. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Extrapyramidal Symptom Rating Scale (ESRS), and side effect checklist. Results The patients’ baseline characteristics were comparable between the groups. There was a significant time-treatment interaction effect on PANSS negative subscale scores (ηP2=0.075), with the pentoxifylline group showing significantly greater reductions until weeks 4 (Cohen’s d=0.512) and 8 (Cohen’s d=0.622). Also, this group showed a significantly better response by week 8. Other PANSS scores, HDRS scores, ESRS scores, and side effect frequencies were comparable between the groups. Pentoxifylline showed a non-significant higher remission of 37.1% compared to 14.7% in the placebo group. Conclusions Pentoxifylline was beneficial for the primary negative symptoms of chronic schizophrenia safely and tolerably.

Plasma microRNAs Associate Positive, Negative, and Cognitive Symptoms with Inflammation in Schizophrenia.

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.

Crocus sativus (saffron) adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled trial.

Current treatments for schizophrenia encounter resistance, limited efficacy, and limiting complications, necessitating novel approaches. The effects of saffron on negative symptoms were investigated as it has shown neuroprotective and antipsychotic properties. Fifty-six clinically stable chronic schizophrenic outpatients were equally assigned to saffron 15 mg q12hr or placebo groups while continuing risperidone. The Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia-related symptoms in weeks 4 and 8. Also, the patients were assessed for the Hamilton depression rating scale (HDRS) and adverse effects. The baseline characteristics of the groups were comparable (Ps > 0.05). There were significant time-treatment interaction effects on negative ( = 0.137), general psychopathology ( = 0.193), and total ( = 0.113) PANSS scores. Affirmatively, their reductions were significantly greater in the saffron group until weeks 4 (Cohen's ds = 0.922, 0.898, and 0.759, respectively) and 8 (Cohen's ds = 0.850, 1.047, and 0.705, respectively). Regarding the negative symptoms, a better 25% response rate was obtained in the saffron group until the endpoint (P = 0.003). The HDRS scores, extrapyramidal symptom rating scale scores, and side effect frequencies were comparable between the groups (Ps > 0.05). Saffron was beneficial for primary negative symptoms of chronic schizophrenia in a safe and tolerable manner. It also outperformed placebo in improving general psychopathology and total symptoms.

Longitudinal evaluation of the early auditory gamma-band response and its modulation by attention in first-episode psychosis.

Executive control over low-level information processing is impaired proximal to psychosis onset with evidence of recovery over the first year of illness. However, previous studies demonstrating diminished perceptual modulation via attention are complicated by simultaneously impaired perceptual responses. The present study examined the early auditory gamma-band response (EAGBR), a marker of early cortical processing that appears preserved in first-episode psychosis (FEP), and its modulation by attention in a longitudinal FEP sample. Magnetoencephalography was recorded from 25 FEP and 32 healthy controls (HC) during active and passive listening conditions in an auditory oddball task at baseline and follow-up (4-12 months) sessions. EAGBR inter-trial phase coherence (ITPC) and evoked power were measured from responses to standard tones. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). There was no group difference in EAGBR power or ITPC. While EAGBR ITPC increased with attention in HC, this modulation was impaired among FEP. Diminished EAGBR modulation in FEP persisted at longitudinal follow-up. However, among FEP, recovery of EAGBR modulation was associated with reduced PANSS negative scores. FEP exhibit impaired executive control over the flow of information at the earliest stages of sensory processing within auditory cortex. In contrast to previous work, this deficit was observed despite an intact measure of sensory processing, mitigating potential confounds. Recovery of sensory gain modulation over time was associated with reductions in negative symptoms, highlighting a source of potential resiliency against some of the most debilitating and treatment refractory symptoms in early psychosis.

Deficits in prosodic speech-in-noise recognition in schizophrenia patients and its association with psychiatric symptoms

BackgroundUncertainty in speech perception and emotional disturbances are intertwined with psychiatric symptoms. How prosody embedded in target speech affects speech-in-noise recognition (SR) and is related to psychiatric symptoms in patients with schizophrenia (SCHs) remains unclear. This study aimed to examine the neural substrates of prosodic SR deficits and their associations with psychiatric symptom dimensions in patients with schizophrenia.MethodsFifty-four SCHs and 59 healthy control participants (HCs) completed the SR task (participants were required to identify the contents of the target pseudo-sentences expressed in neutral, happy, sad, angry, fearful, and disgusted prosody by actors), positive and negative syndrome scale (PANSS) assessment, and magnetic resonance imaging scanning. We examined the deficits of the six prosodic SRs in schizophrenia patients and their associations with brain gray matter volume (GMV) and psychiatric symptoms.ResultsNegative emotional (sad, angry, fearful, and disgusted) prosodies of the target sentences worsened SR across groups. Both participant groups had equal SR between the neutral and happy prosody conditions. Compared to the anger and disgusted conditions, SCHs and HCs had better SR under sad and fearful conditions. Better prosodic SR was associated with shorter duration and lower local shimmer of target sentences. A partial least squares (PLS) component of GMV (covering 47 brain regions with group differences) was associated with six prosodic SRs. The happy SR was associated with the PANSS total, negative, and general scores, adjusting for covariates.ConclusionsNegative emotional prosodies of the target sentences dampened the recognition of the target sentences. The prosodic SR abnormalities in SCHs were associated with not only brain GMV reductions in the regions involved in the processing of sensorimotor, speech, and emotion but also with negative and general psychiatric symptoms. These findings suggest the possibility of improving negative symptoms by improving a happy SR in schizophrenia patients based on neuroplasticity.

"Short" Versus "Long" Duration of Untreated Psychosis in People with First-Episode Psychosis: A Systematic Review and Meta-Analysis of Baseline Status and Follow-Up Outcomes.

Duration of untreated psychosis (DUP) has been linked to worse mental health outcomes in psychotic disorders. We meta-analytically studied the relationship between "long" vs. "short" DUP and mental health outcomes. This PRISMA/MOOSE-compliant meta-analysis searched for nonoverlapping individual studies from database inception until November 01, 2023, reporting data from author-defined "short"/"long" DUP (according to author's definition) in patients with first-episode psychosis (FEP). We compared differences between "short"/"long" DUP groups at baseline and/or follow-up in continuous and binary outcomes. We conducted random-effects meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO: CRD42023479321). From 16,055 citations, 34 studies were included (n = 6,425, age = 27.5 ± 7.1 years, males = 60.4%, white = 70.2%, DUP: mean = 60.8 ± 43.8 weeks, median = 52.5, interquartile range = 31.3, 68.0 weeks, follow-up = 19.2 ± 35.0 months). The definition of "short"/"long" varies significantly between the studies. Compared to "short" DUP (mean = 10.2 ± 11.2 weeks), "long" DUP (mean = 58.8 ± 76.4 weeks) was associated with higher baseline Positive and Negative Syndrome Scale (PANSS) negative (k = 14, ES = 0.45, 95%CI = 0.16, 0.74) and Scale for the Assessment of Negative Symptoms (k = 7, ES = 0.29, 95%CI = 0.11, 0.47) scores, lower remission (k = 7, OR = 0.40, 95%CI = 0.24, 0.67) and more suicide attempts (k = 4, OR = 2.01, 95%CI = 1.36, 2.96). At follow-up, compared to "short" DUP, "long" DUP was associated with lower Global Assessment of Functioning (k = 4, ES = -0.63, 95%CI = -0.83, -0.43) and higher PANSS negative subscale scores (k = 5, ES = 0.66, 95%CI = 0.05, 1.27). In FEP, longer DUP is related to greater baseline negative symptoms, less remission, and more suicide attempts, as well as greater postbaseline negative symptom severity and functional disability. To what degree longer DUP contributes to poorer outcomes or whether DUP only correlates with these outcomes requires further study. A greater consensus on the definition of long DUP is needed to make comparisons between studies more feasible.

Effects of 6-week olanzapine treatment on serum IL-2, IL-4, IL-8, IL-10, and TNF-α levels in drug-naive individuals with first-episode schizophrenia

BackgroundSchizophrenia is a complex neuropsychiatric disorder. Growing evidence indicates that the activation of the inflammatory response system with interleukin (IL)-2, IL-4, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of schizophrenia,. However, clinical data on cytokine levels in patients with schizophrenia treated with antipsychotics are inconsistent or inconclusive. In this study, we have examined inflammatory factors’ alterations and their relationship to changes in clinical symptoms before and after olanzapine treatment of drug-naive patients with first-episode schizophrenia.MethodsWe recruited 142 hospitalized patients with first-episode schizophrenia as a study group; blood samples were collected, and the patients were assessed for clinical symptoms at baseline and after 6 weeks of olanzapine treatment. One hundred individuals with no history of mental illness were also recruited as healthy controls. Blood samples were collected, and the serum levels of IL-2, IL-4, IL-8, IL-10, and TNF-α were determined using an enzyme cycling assay. The severity of clinical symptoms was assessed according to the Positive and Negative Syndrome Scale (PANSS).ResultsIndividuals with schizophrenia had lower IL-8 levels and higher IL-10 levels than healthy controls (P < 0.001). Positive correlations were detected between serum IL-2 and IL-10 concentrations and each subscale of the PANSS (all P < 0.05). Moreover, a negative correlation existed between the serum IL-8 concentration and the PANSS negative score (r = − 0.172, P = 0.040). After 6 weeks of treatment, serum IL-8 levels in the patient group were lower than at baseline (P < 0.001), whereas serum IL-10 and TNF-α levels were higher than at baseline (all P < 0.05). Therefore, serum IL-10 can be determined as an independent risk factor for outcome in patients with first-episode schizophrenia (P = 0.02, OR = 2.327). Furthermore, serum IL-2, IL-10, and TNF-α levels were significantly lower, whereas the serum IL-8 level was significantly higher (P < 0.001) in the healthy control group than in the “response” and “no-response” treatment groups respectively.ConclusionsOur results indicate that serum IL-2, IL-8, IL-10, and TNF-α levels may be involved in the pathophysiological mechanisms of schizophrenia and correlate with the effects of olanzapine.

Sex-specific associations between 10-year cardiovascular risk, clinical symptoms and cognitive impairments in schizophrenia.

Schizophrenia (SCZ) shortens life expectancy, with cardiovascular disease (CVD) as the leading cause of death. The links between psychiatric symptoms, cognitive function and CVD are unclear, and sex differences in this relationship are understudied. This study examined the relationship between clinical characteristics and 10-year cardiovascular risk in males and females with SCZ. This study included 802 patients with chronic SCZ. Fasting venous blood samples were collected from all patients to measure relevant glycolipid metabolic indices. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Framingham risk score (FRS) was used to estimate the 10-year CVD risk. The mean 10-year cardiovascular risk for all patients was 11.76 ± 8.99%. Among patients with SCZ, 52.8% exhibited an intermediate-high 10-year cardiovascular risk. Multivariate linear regression analysis showed that FRS increased with higher body mass index, blood pressure, glucose, total cholesterol and triglyceride levels, while it was inversely related to high density lipoprotein levels. The general psychopathological scores were negatively associated with FRS (male: B = -0.086, P = 0.013; female: B = -0.056, P = 0.039). Negative symptom (B = -0.088, P = 0.024) and total PANSS scores (B = -0.042, P = 0.013) showed a negative association with FRS only in males. Additionally, in patients over 60years old, general psychopathology (B = -0.168, P = 0.001) and PANSS total scores (B = -0.057, P = 0.041) were associated with reduced FRS, while immediate memory (B = 0.073, P = 0.025) was associated with higher FRS. Patients with SCZ have an elevated risk of developing CVD, with males showing a higher 10-year cardiovascular risk than females. Significant sex differences exist in the relationship between the FRS and psychiatric symptoms, with negative symptoms being negatively related to FRS only in males.

Peripersonal Space Plasticity in Relation to Psychopathology and Anomalous Subjective Experiences in Individuals With Early-Onset and Adult-Onset Schizophrenia.

Individuals with schizophrenia present anomalies in the extension and plasticity of the peripersonal space (PPS), the section of space surrounding the body, shaped through motor experiences. A weak multisensory integration in PPS would contribute to an impairment of self-embodiment processing, a core feature of the disorder linked to specific subjective experiences. In this exploratory study, we aimed at: (1) testing an association between PPS features, psychopathology, and subjective experiences in schizophrenia; (2) describing the PPS profile in individuals with early-onset schizophrenia. Twenty-seven individuals with schizophrenia underwent a task measuring the PPS size and boundaries demarcation before and after a motor training with a tool. The Positive And Negative Syndrome Scale (PANSS), the Examination of Anomalous Self Experience scale (EASE) and the Autism Rating Scale (ARS) were used to assess psychopathology. Subsequently, participants were divided into two subgroups, early and adult-onset schizophrenia. The two groups were compared in regard to their PPS and psychopathological profiles. PPS patterns were associated with psychopathology, particularly positively with PANSS negative scale score, and negatively with subjective experiences of existential reorientation (EASE Domain 5 scores) and of social encounters (ARS scores). Only PPS parameters and ARS scores differentiated between early and adult-onset participants. Our results, although preliminary and exploratory, can suggest a link between PPS patterns, negative symptoms, and disturbances of the subjective experience, particularly in the intersubjective domain, in schizophrenia. Moreover, they seem to suggest that specific PPS profiles and schizophrenic autism traits could be markers of early-onset schizophrenia.

The potential predictive value and relationship of blood-based inflammatory markers with the clinical symptoms of Han Chinese patients with first-episode adolescent-onset schizophrenia.

Inflammation is associated with the pathophysiology of schizophrenia. The blood markers for systemic inflammation include neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR), system inflammation response index (SIRI), and platelet-lymphocyte ratio (PLR). However, these inflammation markers and their relationships with clinical phenotypes among Han Chinese patients with first-episode adolescent-onset schizophrenia (AOS) is unclear. This investigation aimed to elucidate the impact of inflammation on Han Chinese AOS patients as well as the association of blood-based inflammation markers with clinical symptoms. Altogether, 203 Han Chinese individuals participated in this study, 102 first-episode AOS patients and 101 healthy controls. The assessment of inflammatory indices was based on complete blood cell count. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS). In Han Chinese first-episode AOS patients, levels of SIRI, PLR, SII, and NLR were significantly increased (p < 0.001), while LMR decreased (p < 0.001) compared to healthy controls. Furthermore, multivariate logistic regression showed that LMR, NLR, SII, and SIRI (all p < 0.05) were independently associated with AOS. Moreover, Receiver operating characteristics assessment indicated that NLR, SIRI, LMR, and SII could effectively distinguish AOS patients from healthy controls. Their areas under the curves were 0.734, 0.701, 0.715, and 0.730 (all p < 0.001). In addition, Correlation analysis revealed that LMR was negatively correlated with the PANSS total, negative, and cognitive factor scores (all p < 0.05); NLR was positively correlated with the cognitive factor score (p < 0.01); SII was negatively correlated with the positive factor score and positively with the negative and cognitive factor scores (all p < 0.05); SIRI was positively correlated with the PANSS total and cognitive factor scores (all p < 0.01). This research established the involvement of peripheral blood inflammatory markers (LMR, NLR, SII, and SIRI) with the clinical manifestations and pathophysiology of schizophrenia, and these can serve as screening tools or potential indices of the inflammatory state and AOS symptoms severity.

Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.

Several lines of evidence indicate that an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) gene may be involved in the pathogenesis of schizophrenia and cognitive impairment. However, the relationship between ACE I/D polymorphism and cognitive impairment in patients with schizophrenia remains unclear. The aim of this study was to examine whether ACE gene I/D polymorphism contributed to cognitive impairment in Chinese patients with schizophrenia, and whether the association between clinical symptoms and cognitive impairment depended on different ACE genotypes. The ACE I/D polymorphism was genotyped in 928 schizophrenia patients and 325 healthy controls using a case-control design. The severity of psychopathological symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant differences in genotype and allele frequencies of the ACE I/D polymorphism between patients and healthy controls (both P < 0.01). After controlling for demographic characteristics, patients who are homozygous carriers of D and I performed worse on the RBANS attention index than heterozygous carriers (P = 0.009). In addition, attention index score was negatively correlated with PANSS negative symptom score in patients of all genotypes (all P < 0.05), and positively correlated with positive symptom score only in the I/I genotype (P = 0.005). These findings suggest that ACE I/D gene variants play a role in susceptibility to schizophrenia, specific cognitive impairment and the association between clinical symptoms and cognitive impairment in schizophrenia patients.

Correlation Between Severity of Schizophrenia with Certain Trace Elements and TNF-α Gene Expression and Its Circulatory Level in the Population of Western India.

This cross-sectional study aimed to assess serum trace element (TE) concentrations, TNF-α gene expression, protein levels in schizophrenia (SZ) patients, and their correlation with disease severity measured by Positive and Negative Syndrome Scale (PANSS) scores. Forty SZ cases and 40 healthy controls aged 18-60 were recruited. Forty (n = 40) cases who meet ICD-10 criteria for SZ and 40 (n = 40) healthy individuals (controls) between 18 and 60years of age were recruited in the study. Sandwich enzyme-linked immunosorbent assay (ELISA) and RT-qPCR (quantitative real-time PCR) were used to estimate pro-inflammatory cytokine TNF-α protein and gene expression. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) and graphite furnace atomic absorption spectroscopy (GFAAS) were used to assess serum levels of trace elements (TEs): Fe, Zn, Cu, Mg, and Se. Compared to healthy controls, cases had significantly higher levels of TNF-α protein, as well as Fe, Cu, and Se (p < 0.05). Cu correlated positively with TNF-α protein level (rho = 0.234; p = 0.048) and gene expression (rho = 0.333; p = 0.041) and with PANSS negative (rho = 0.531), general (rho = 0.643), and total (rho = 0.541) scores. Additionally, Zn negatively correlated with serum Mg (rho = - 0.426, p < 0.01) and positively with serum Se (rho = 0.343, p < 0.05). In conclusion, elevated Cu levels could potentially contribute to the development of SZ. Elevated Cu levels in cases and their correlation with the TNF-α gene and protein and PANSS score indicate Cu's potential role in exacerbating SZ severity through inflammatory cytokines. This suggests the involvement of metals and cytokines in the pathophysiology of SZ.

A comparison of clinical characteristics and course predictors in early- and childhood-onset schizophrenia.

The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis. Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course. Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families.

Cariprazine in the management of emotionally unstable personality disorder in female patients: a case series.

Emotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited. To evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent. Demographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months. Eight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3-6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up. This is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.

A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis Using Normative Models.

Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

Short-term antipsychotic treatment reduces functional connectivity of the striatum in first-episode drug-naïve early-onset schizophrenia

BackgroundThe striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. MethodsWe recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. ResultsCompared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. ConclusionsDecreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia.

Mapping Brain Synergy Dysfunction in Schizophrenia: Understanding Individual Differences and Underlying Molecular Mechanisms.

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean-field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

Statins as an adjuvant therapy for patients with schizophrenia: An up-to-date systematic review and meta-analysis

BackgroundEvidence suggests that inflammatory processes play a role in the pathophysiology of schizophrenia. Statins exert anti-inflammatory and antioxidant effects and may be effective in improving the symptoms of schizophrenia. This study explored whether statins, as an adjunctive therapy, can alleviate the symptoms of schizophrenia. MethodsPubMed, EMBASE, and the Cochrane Library were searched for articles published up to March 2023. The risk-of-bias tool for randomized trials was used to assess study quality. Two researchers independently assessed the risks of bias and extracted data. Pooled data on Positive and Negative Syndrome Scale (PANSS) scores were analyzed. A random-effects model was employed to calculate pooled effect sizes. Statistical heterogeneity across studies was assessed using the I2 statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software. ResultsNine trials enrolling 533 patients in total were included. Add-on statin therapy was found to be associated with a significantly better total PANSS score [standardized mean difference (SMD) = −0.42, 95% confidence interval (CI) −0.75 to −0.09, I2 = 72%; P = 0.01] and PANSS negative subscale score (SMD = −0.26, 95% CI −0.45 to −0.07, I2 = 0%; P = 0.009) in comparison with placebo. However, add-on statin therapy did not appear to improve scores for the PANSS positive and general subscales at the study-defined endpoint (6–24 weeks). ConclusionsOur meta-analysis indicates that adjunctive statin therapy may confer benefits in ameliorating PANSS negative and total scores. It needs more solid data to confirm the results are related to clinical improvement and functioning.

Quality of Life and C-Reactive Protein in Patients with Schizophrenia: A Cross-Sectional Study.

The connection between chronic inflammation and the quality of life (QOL) in individuals diagnosed with schizophrenia lacks clarity. This study aimed to achieve 2 primary objectives: (1) assess the QOL among outpatients with schizophrenia and (2) explore the potential correlation between reduced QOL and heightened levels of C-reactive protein (CRP) in patients with schizophrenia. The research included 129 outpatients diagnosed with schizophrenia who were receiving care at the psychiatry department of the University Hospital Mohamed VI in Marrakech, Morocco. Disease severity was evaluated using the Positive and Negative Syndrome Scale (PANSS), while the QOL was measured using the Moroccan Arabic version of The Schizophrenia Quality of Life questionnaire. Patients were categorized into 2 groups based on their CRP levels: normal CRP (≤5.0 mg/L) and high CRP (>5.0 mg/L). A comparative analysis of sociodemographic, clinical, biological, and quality of life factors was conducted between the 2 groups (normal CRP and high CRP). The group with elevated CRP levels exhibited higher scores in various PANSS categories, including PANSS total score (P ≤ .01), PANSS positive score (P ≤ .01), PANSS negative score (P ≤ .01), and PANSS general score (P ≤ .01). After adjusting for sociodemographic and clinical variables, individuals with elevated CRP levels demonstrated lower QOL compared to those with normal CRP levels (OR = 0.57, 95% CI = 0.46-0.68). Significant associations were noted between male gender (OR = 0.047, 95% CI = 0.01-0.26), earlier onset of the condition (OR = 0.54, 95% CI = 0.33-0.82), current tobacco smoking (OR = 0.015, 95% CI = 0.00-0.08), and heightened CRP levels. Our study suggests that higher CRP is associated with lower QOL levels in schizophrenia.

Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia

A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. To evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia. EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups. Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity. ClinicalTrials.gov Identifier: NCT04738123.