Negative Symptom Scale Research Articles

Decreased serum VEGF and NRG1β1 levels in male patients with chronic schizophrenia: VEGF correlation with clinical symptoms and cognitive deficits

BackgroundVascular endothelial growth factor (VEGF) and neuregulin1 (NRG1) are multifunctional trophic factors reported to be dysregulated in schizophrenia. However, the relationships between serum concentrations and schizophrenia symptoms have differed markedly across studies, possibly because schizophrenia is a highly heterogenous disorder. The aim of this study was to investigate the associations of serum VEGF and NRG1 with clinical symptoms and cognitive deficits specifically in male patients with chronic schizophrenia. MethodsThe study included 79 male patients with chronic schizophrenia and 79 matched healthy individuals. Serum VEGF, NRG1β1, S100B, S100A8, and neuropilin1 were measured using the Luminex liquid suspension chip detection method, psychopathological symptom severity using the Positive and Negative Symptom Scale (PANSS), and cognitive dysfunction using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). ResultsSerum VEGF and NRG1β1 concentrations were significantly lower in male chronic schizophrenic patients than healthy controls (P < 0.05), while serum S100B, S100A8, and neuropilin1 concentrations did not differ between groups (P > 0.05). Serum VEGF concentration was negatively correlated with PANSS negative subscore (beta = −0.220, t = −2.07, P = 0.042), general psychopathology subscore (beta = -0.269, t = −2.55, P = 0.013), and total score (beta = -0.234, t = −2.12, P = 0.038), and positively correlated with RBANS language score (beta = 0.218, t = 2.03, P = 0.045). Alternatively, serum NRG1β1 concentration was not correlated with clinical symptoms or cognitive deficits (all P > 0.05). ConclusionDysregulation of VEGF and NRG1β1 signaling may contribute to the pathogenesis of chronic schizophrenia in males. Moreover, abnormal VEGF signaling may contribute directly or through intermediary processes to neuropsychiatric and cognitive symptom expression.

Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom–Dominant Psychosis

Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge. To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis. This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023. Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD. Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002). The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

Prevalence of metabolic syndrome and its associated factors in first-treatment drug-naïve schizophrenia patients: A large-scale cross-sectional study.

Metabolic syndrome (MetS), a condition that includes several risk factors specific for cardiovascular disease, is commonly detected among patients with schizophrenia (SCZ). This study elucidated the factors contributing to the development and severity of MetS in first-treatment drug-naïve (FTDN) patients with SCZ. The study enrolled 668 individuals with FTDN SCZ, aged 18-49 years, who had no exposure to antipsychotic medications and been hospitalized between February 2017 and June 2022 at the largest psychiatric specialty institution in central China. Patient sociodemographic and general clinical data were collected, and their psychopathology scores and illness severity were assessed using the Positive and Negative Symptom Scale (PANSS) and Clinical Global Impression Scale-Severity of Illness (CGI-SI), respectively. MetS score was calculated to determine the disease severity. The prevalence of MetS among this study population was 10.93%. Binary logistic regression analysis revealed onset age, female sex, total cholesterol, and red blood and white blood cell counts as risk factors for MetS, and deemed free tetraiodothyronine (FT4) and CGI-SI score as protective factors. Multiple linear regression analysis result confirmed older SCZ onset age as a risk factor for elevated MetS score. This study determined the prevalence of MetS in patients with FTDN SCZ and revealed the factors that influence the occurrence and severity of the disease. These findings will allow development of specific prevention and treatment strategies in clinical practice.

A 12-month longitudinal naturalistic follow-up of cariprazine in schizophrenia.

Cariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world literature data are lacking, particularly when exploring its efficacy in the long term. The present study examined the effects of cariprazine treatment on specific psychopathological domains with a particular focus on outcomes and side effects in real-life experience, after a long-term treatment. The present 12-month longitudinal naturalistic study included a sample of subjects with a DSM-5-TR diagnosis of schizophrenia, recruited in the outpatients' psychiatric services of university and community hospitals in Italy, naturally treated with cariprazine. The assessments included: a sociodemographic data sheet, the Structured Clinical Interview for the DSM-5 (SCID-5), the Positive and Negative Symptom Scale (PANSS) and the St. Hans Rating Scale (SHRS). The PANSS was also administered after 6 (T1) and 12 (T2) months of treatment with cariprazine while the SHRS at T1. The total sample consisted of 31 patients, 15 males and 16 females. A significant decrease of the PANSS' subscales, Marder factors and total mean scores emerged at both T1 and T2 with respect to T0. Extrapyramidal symptoms occurred in a minority of patients and in mild or mild/moderate forms: no patient showed moderate forms of psychic/motor akathisia or dystonia, three subjects showed moderate parkinsonism. This study confirms a good efficacy profile of cariprazine in both positive and negative symptoms in patients with Schizophrenia, combined with a good tolerability profile in extrapyramidal symptoms.

Targeted metabolomics-based understanding of the sleep disturbances in drug-naïve patients with schizophrenia

BackgroundSleep disturbances are a common occurrence in patients with schizophrenia, yet the underlying pathogenesis remain poorly understood. Here, we performed a targeted metabolomics-based approach to explore the potential biological mechanisms contributing to sleep disturbances in schizophrenia.MethodsPlasma samples from 59 drug-naïve patients with schizophrenia and 36 healthy controls were subjected to liquid chromatography-mass spectrometry (LC-MS) targeted metabolomics analysis, allowing for the quantification and profiling of 271 metabolites. Sleep quality and clinical symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Positive and Negative Symptom Scale (PANSS), respectively. Partial correlation analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) model were used to identify metabolites specifically associated with sleep disturbances in drug-naïve schizophrenia.Results16 characteristic metabolites were observed significantly associated with sleep disturbances in drug-naïve patients with schizophrenia. Furthermore, the glycerophospholipid metabolism (Impact: 0.138, p<0.001), the butanoate metabolism (Impact: 0.032, p=0.008), and the sphingolipid metabolism (Impact: 0.270, p=0.104) were identified as metabolic pathways associated with sleep disturbances in drug-naïve patients with schizophrenia.ConclusionsOur study identified 16 characteristic metabolites (mainly lipids) and 3 metabolic pathways related to sleep disturbances in drug-naïve schizophrenia. The detection of these distinct metabolites provide valuable insights into the underlying biological mechanisms associated with sleep disturbances in schizophrenia.

Classification of Neurocognition in Japanese Patients with Schizophrenia: A Cluster Analysis

Objectives. Cognitive functions in almost all domains are lower in patients with schizophrenia than those in healthy controls, with the severity of impairment differing between domains. Treatments are being developed to improve cognitive impairment in patients with schizophrenia. However, the pattern of cognitive impairment must be clarified to facilitate treatment. Therefore, this study aimed to classify the patterns of cognitive impairment in individuals and provide treatment suggestions. Methods. Patients with schizophrenia were recruited from two psychiatric hospitals in Japan. Demographic and psychopathological symptoms were assessed using the Positive and Negative Symptoms Scale for Schizophrenia and neurocognitive functions, using the CogHealth battery. The following domains were assessed: processing speed, visual attention, working memory, visual learning, and spatial attention. The scores were standardised and assigned as the same-aged average score. Hierarchical cluster analysis using Ward’s method was performed based on CogHealth scores. Subsequently, one-way analysis of variance (ANOVA) and Tukey’s multiple comparisons were performed to compare the variables in each cluster. Results. In total, 133 participants were classified into four clusters: Cluster 1 (n = 16), with severe cognitive impairment and psychiatric symptoms and the longest stay; Cluster 2 (n = 44), with moderate cognitive impairment and psychiatric symptoms; Cluster 3 (n = 42), with preserved cognitive function, except for spatial perception, and mild psychiatric symptoms; and Cluster 4 (n = 31), with only memory and spatial perception impairment and mild psychiatric symptoms. Implications. The clusters indicate that impairment may occur in all or selective domains. Selective domain impairments may be in spatial perception or in spatial perception and memory. Therefore, it is recommended that treatments for cognitive dysfunction are developed into four subsets considering an individual’s cognitive features.

Effects of transcranial direct current stimulation (tDCS) on positive and negative symptoms in patients with schizophrenia

Effects of transcranial direct current stimulation (tDCS) on positive and negative symptoms in patients with schizophrenia

Aberrant salience mediates the interplay between emotional abuse and positive symptoms in schizophrenia

IntroductionChildhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. MethodsWe approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. ResultsThe final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (β = 0.39; p < .001) and from ASI total score to PANSS positive (β = 0.17; p = .019). Finally, a statistically significant indirect association was found from emotional abuse to PANSS positive mediated by ASI total score (β = 0.06; p = .041; CI 95% [0.01, 0.13]). ConclusionEmotional abuse has an AS-mediated effect on positive psychotic symptomatology. AS evaluation could allow a better characterization of psychosis as well as explain the presence of positive symptoms in adults with SSDs who experienced CTA.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Pharmacogenetic intervention improves treatment outcomes in Chinese adult men with schizophrenia

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions–Severity of Illness scale (CGI-SI) and Clinical Global Impressions–Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96–11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders.In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia.

Effort-cost decision-making associated with negative symptoms in schizophrenia and bipolar disorder

Motivational deficits and reduced goal-directed behavior for external rewards have long been considered an important features of negative symptoms in patients with schizophrenia (SCZ). Negative symptoms have also a high prevalence in bipolar disorder (BP). We used a transdiagnostic approach in order to examine association between negative symptoms and effort allocation for monetary rewards. 41 patients with SCZ and 34 patients with BP were enrolled in the study along with 41 healthy controls (HC). Effort-Expenditure for Rewards Task (EEfRT) was used to measure subjects' effort allocation for monetary rewards. Generalized estimating equation models were used to analyze EEfRT choice behavior. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). SCZ and BP groups expended lower effort to obtain a monetary rewards compared to HC. Severity of negative symptoms was negatively correlated with EEfRT performance in both diagnostic groups. Each diagnostic group showed lower effort allocation for monetary rewards compared to HC suggesting reduced motivation for monetary rewards. In addition, our results suggest that abnormal effort-based decision-making might be a transdiagnostic factor underlying negative symptoms.

Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia

BackgroundGlutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels.MethodsEnzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB).ResultThe levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction.ConclusionOur findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

Clinical and cognitive factors associated to insight in first psychotic episodes

IntroductionInsight is a field of interest in psychosis, due to its influence on the course and prognosis of the desease and as well as adherence to treatment.ObjectivesThe present work aims to evaluate the influence of cognitive and psychopathological variables on awareness of illness in first psychotic episodes.MethodsIt is a cross-sectional study of a sample of 26 patients with diagnosis of a first psychotic episode admitted in a Brief Hospitalization Unit, who have been evaluated using the Positive and Negative Symptom Scale (PANSS), the Screening for Cognitive Impairment (SCIP) and the Scale of Non-awareness of Mental Disorder (SUMD).ResultsA positive correlation was found between SUMD and negative PANSS (the worse insight, the greater negative psychopathology) and between the level of cognitive performance and the awareness of having negative symptoms (affective blunting, anhedonia and associability) and their attribution to the desease.ConclusionsThis findings suggest the importance of addressing awareness of negative symptoms from the first episodes in psychoeducational family therapy and rehabilitation programs, taking into account that this process is hindered by the cognitive dysfunctions.Disclosure of InterestNone Declared

Validation of the rating scales for negative symptoms: new strategies

AbstractNegative symptoms of schizophrenia are linked with poor functioning and quality of life. Therefore, appropriate measurement tools to assess negative symptoms are needed. The NIMH-MATRICS Consensus defined five domains for negative symptoms. We used the COSMIN guidelines for systematic reviews to evaluate the quality of psychometric data of negative symptom scales as Clinician-Rated Outcome Measure (ClinROM). COSMIN assesses risk of bias, so called updated criteria of measurement properties, a modified GRADE approach and a final judgement on the rating scale. In the lecture the process will be described using the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms (CAINS) as examples.Disclosure of InterestNone Declared

485 Investigating the Impact of Inflammation on White Matter Tracts using Diffusion Tensor Imaging that may Contribute to Motivational Deficits and Negative Symptoms in Patients with Schizophrenia

OBJECTIVES/GOALS: Previous research has linked inflammation to changes in brain reward circuitry and subsequent negative symptoms in patients with schizophrenia. This project aims to understand brain-immune interactions using diffusion tensor imaging (DTI) to investigate the impact of inflammatory markers on white matter (WM) tracts. METHODS/STUDY POPULATION: Patients with schizophrenia, ages 18 to 45, were recruited at Grady Hospital in Atlanta, GA. All subjects were stable outpatients and underwent extensive medical screening to rule out medical causes of acute inflammation. DTI data was collected from 39 participants on a 3-Tesla Siemens scanner. Blood was collected between 9-11AM for later assay of serum inflammatory markers. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). A diffusion tensor imaging model will be fitted with the data to generate well-known diffusion tensor measures (fractional anisotropy and mean diffusivity). Linear regression will be used to analyze the relationship between DTI measures and inflammation (C-Reactive Protein, CRP), controlling for possible confounders. RESULTS/ANTICIPATED RESULTS: The hypothesis of this proposal is that decreased microstructural integrity in WM tracts between the nucleus accumbens (NAc) and insula will be associated with increased inflammation, which in turn are associated with increased negative symptoms. Negative symptoms include deficits in motivation/pleasure as well as diminished expressivity, and are strongly associated with poor functional outcomes. Based on previous data from this sample demonstrating relationships between CRP and negative symptoms as well as CRP and fMRI functional connectivity between the NAc and insula, we anticipate results that demonstrate similar relationships with WM microstructural integrity, such as functional anisotropy and mean diffusivity. DISCUSSION/SIGNIFICANCE: Given the lack of treatment options for negative symptoms, this research will provide key data to further our understanding of the potential role of inflammation on neural circuits that underlie these symptoms, including WM integrity. This research also has the potential to inform future anti-inflammatory therapies for patients with schizophrenia.

Comparing the latent state–trait structure of the PANSS in cariprazine-medicated and placebo-controlled patients with acute schizophrenia

After over a hundred years of research, the question whether the symptoms of schizophrenia are rather trait-like (being a relatively stable quality of individuals) or state-like (being substance to change) is still unanswered. To assess the trait and the state component in patients with acute schizophrenia, one group receiving antipsychotic treatment, the other not. Data from four phase II/III, 6-week, randomized, double-blind, placebo-controlled trials of similar design that included patients with acute exacerbation of schizophrenia were pooled. In every trial, one treatment group received a third-generation antipsychotic, cariprazine, and the other group placebo. To assess symptoms of schizophrenia, the Positive and Negative Symptom Scale (PANSS) was applied. Further analyses were conducted using the five subscales as proposed by Wallwork and colleagues. A latent state–trait (LST) model was developed to estimate the trait and state components of the total variance of the observed scores. All symptom dimensions behaved more in a trait-like manner. The proportions of all sources of variability changed over the course of the observational period, with a bent around weeks 3 and 4. Visually inspected, no major differences were found between the two treatment groups regarding the LST structure of symptom dimensions. This high proportion of inter-individual stability may represent an inherent part of symptomatology that behaves independently from treatment status.

Automated linguistic analysis in speech samples of Turkish-speaking patients with schizophrenia-spectrum disorders

Modern natural language processing (NLP) methods provide ways to objectively quantify language disturbances for potential use in diagnostic classification. We performed computerized language analysis in speech samples of 82 Turkish-speaking subjects, including 44 patients with schizophrenia spectrum disorders (SSD) and 38 healthy controls (HC). Exploratory analysis of speech samples involved 16 sentence-level semantic similarity features using SBERT (Sentence Bidirectional Encoder Representation from Text) as well as 8 generic and 8 part-of-speech (POS) features. The random forest classifier using SBERT-derived semantic similarity features achieved a mean accuracy of 85.6 % for the classification of SSD and HC. When semantic similarity features were combined with generic and POS features, the classifier's mean accuracy reached to 86.8 %. Our analysis reflected increased sentence-level semantic similarity scores in SSD. Generic and POS analyses revealed an increase in the use of verbs, proper nouns and pronouns in SSD while our results showed a decrease in the utilization of conjunctions, determiners, and both average and maximum sentence length in SSD compared to HC. Quantitative language features were correlated with the expressive deficit domain of BNSS (Brief Negative Symptom Scale) as well as with the duration of illness. These findings from Turkish-speaking interviews contribute to the growing evidence-based NLP-derived assessments in non-English-speaking patients.

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia.

Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between DRD2, HTR2A, SLC6A4, CYP1A2, and ABCB1 polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting SLC6A4, HTR2A, and the *1F/*1F polymorphism for the CYP1A2 gene.

Five-week music therapy improves overall symptoms in schizophrenia by modulating theta and gamma oscillations.

Some clinical studies have shown that music therapy as an adjunctive therapy can improve overall symptoms in patients with schizophrenia. However, the neural mechanisms of this improvement remain unclear due to insufficient neuroimaging evidence. In this work, 17 patients with schizophrenia accepted a five-week music therapy (music group) that integrated listening, singing, and composing, and required patients to cooperate in a group to complete music therapy tasks. Meanwhile, 15 patients with schizophrenia received a five-week visual art intervention as the control group including handicraft and painting activities. We collected the Manchester Scale (MS) and Positive and Negative Symptom Scale (PANSS) scores and electroencephalography (EEG) data before and after intervention in two groups. Behavioral results showed that both interventions mentioned above can effectively help patients with schizophrenia relieve their overall symptoms, while a trend-level effect was observed in favor of music therapy. The EEG results indicated that music therapy can improve abnormal neural oscillations in schizophrenia which is reflected by a decrease in theta oscillation in the parietal lobe and an increase in gamma oscillation in the prefrontal lobe. In addition, correlation analysis showed that in the music group, both reductions in theta oscillations in the parietal lobe and increases in gamma oscillations in the prefrontal lobe were positively correlated with the improvement of overall symptoms. These findings help us to better understand the neural mechanisms by which music therapy improves overall symptoms in schizophrenia and provide more evidence for the application of music therapy in other psychiatric disorders.

Antipsychotic Effects of Celecoxib Add-On Haloperidol in Schizophrenia: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Background: Previous studies have indicated abnormalities in the immune system, such as central nervous system inflammation and high levels of activating cytokines in the cerebrospinal fluid of schizophrenic patients. Celecoxib, a modulator of proinflammatory cytokines, as an adjunctive therapy add-on risperidone (a well-established atypical antipsychotic) and amisulpiride (a benzamide antipsychotic), had improved these patients significantly. Objectives: A trial was conducted to evaluate the therapeutic effects of celecoxib add-on haloperidol, a classic antipsychotic that has been reported to have an immunomodulatory effect and mainly affects positive psychotic symptoms in schizophrenia. Methods: In a prospective, double-blind study, after a washout period, 49 patients with schizophrenia were randomly assigned to either 15 - 30 mg/day haloperidol plus 400 mg/day of celecoxib or the same dose of haloperidol plus placebo for 5 weeks. Psychopathology was evaluated via the Positive and Negative Symptoms Scale (PANSS). The data were reported as mean ± standard deviation and frequency. An Independent t-test was carried out when comparing the data of these two groups for each week. The proportion comparison was carried out using the chi-square test. In terms of age, gender, marital and educational state, and duration or severity of disease or psychopathology and subtypes of schizophrenia, there were no significant differences. Results: Over 5 weeks, there was significantly greater improvement in the celecoxib group in scores on the total PANSS and on positive symptoms and general psychopathology subscales ([t = 2.89, P = 0.006], [t = 2.37, P = 0.022], and [t = 3.34, P = 0.002] respectively). Conclusions: Celecoxib is an efficient adjuvant agent in the treatment of patients with schizophrenia. Significant superiority of management with a modulator of proinflammatory cytokine, which balances immune responses over haloperidol alone, reconfirms the immune dysfunction and inflammation hypothesis of schizophrenia.