PANSS Total Score Research Articles

The economic burden of schizophrenia spectrum disorders: clinical and functional correlates and predictors of direct costs. A retrospective longitudinal study

The economic burden of schizophrenia amounts for 1.5-3 % of healthcare expenses in developed countries, and ∼50 % derives from direct costs: 81 % of these are due to hospitalization, residential facilities and semi-residential facilities. Therefore, a better characterization of variables that influence direct costs represents a relevant issue.A total of 276 individuals with schizophrenia spectrum disorders receiving treatment from the Community Mental Health Centers of Brescia (Italy) were included in the study: for each participant socio-demographic, clinical and functional characteristics were assessed, and data related to the use of services in 2022 (then converted to costs) were collected. Regression analyses were performed to identify predictors of costs.A direct healthcare expenditure of 16477.23 (±32856.47) € per patient per year was identified. The main cost predictor was the PSP total score (p=0.005), followed by age of onset (p=0.020), and PANSS total score (p=0.033). Including PANSS sub-scales scores and PSP single items as potential predictors, the main predictor was the “socially useful activities” PSP item (p=0.002), followed by age of onset (p=0.011), and PANSS negative scale score (p=0.027).Our findings underline the need to implement rehabilitative intervention focused on the improvement of psychosocial functioning and negative symptoms, also to reduce healthcare expenses.

Association between treatment response and dose of blonanserin transdermal patch in patients with acute schizophrenia: A post hoc cluster analysis based on baseline psychiatric symptoms.

To explore the optimal dose of blonanserin transdermal patch (BNS-P) based on baseline psychiatric symptomatic characteristics during acute schizophrenia. A post hoc cluster analysis was conducted using data from a 6-week randomized, double-blind, placebo-controlled study of BNS-P (40 or 80 mg/day) in acute schizophrenia. We classified patients into three clusters based on baseline psychiatric symptoms. Efficacy was assessed using the change from baseline to week 6 in the PANSS total score. Safety was assessed by the incidence of adverse events. Among 577 patients, three clusters were identified, characterized by severe psychiatric (Cluster-S; n = 122), predominant negative (Cluster-N; n = 191), and predominant positive (Cluster-P; n = 264) symptoms. In Cluster-P, both BNS-P 40 and 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.036, effect size = 0.342; p < 0.001, effect size = 0.687, respectively). In Cluster-S and -N, only BNS-P 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.045, effect size = 0.497; p = 0.034, effect size = 0.393, respectively). The effect size was greater at 80 mg/day than at 40 mg/day across all clusters. The most common treatment-emergent adverse events were akathisia and skin-related adverse events in all clusters. BNS-P exhibited a dose-dependent antipsychotic effect in all clusters, particularly highlighting its efficacy in patients with predominant positive symptoms, even at lower doses. These findings provide novel and valuable insights for determining BNS-P dose tailoring to individual symptomatic characteristics in real-world practice.

Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia

Objective: To investigate the correlations of cognitive function with serum levels of homocysteine (Hcy), sex hormone binding globulin (SHBG), and leptin in patients with schizophrenia. Methods: This was retrospective study. This study included 58 patients with schizophrenia (SCZ) as observation group and 60 clinically healthy individuals as control group admitted to Xiangshan County Hospital of Traditional Chinese Medicine Medical and Health Group Third Hospital from March 2022 to June 2023. Serum levels of Hcy, SHBG, and leptin in the two groups were measured, and Pearson correlation analysis was conducted to investigate the correlations between the Hcy, SHBG, and leptin levels and the psychiatric symptoms and cognitive function in the observation group. Results: The Hcy and SHBG levels in the observation group were significantly higher than those in the control group (p&lt;0.05, respectively), and the leptin level was lower than that in the control group (p&lt;0.05). The observation group scored significantly lower than the control group for each dimension of the MCCB (p&lt;0.05, respectively). In the observation group, Hcy was positively correlated with negative symptoms and the PANSS total score (p&lt;0.05, respectively) and was negatively correlated with scores for the leptin was negatively correlated with negative symptoms and the PANSS total score (p&lt;0.05, respectively) and was positively correlated with scores for speed of processing (SOP), WMS-III, BVMT, and MSCEIT (p&lt;0.05, respectively). Conclusions: Increased levels of Hcy and SHBG and decreased leptin are strongly associated with the occurrence of cognitive impairment in SCZ cases. Therefore, clinical observation and monitoring of these markers can help identify changes in patient conditions. doi: https://doi.org/10.12669/pjms.40.10.8923 How to cite this: Xu Y, Qian X, Zhang M, Liang M. Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia. Pak J Med Sci. 2024;40(10):2319-2323. doi: https://doi.org/10.12669/pjms.40.10.8923 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Amphetamine-Induced Dopamine Release Predicts 1-Year Outcome in First-Episode Psychosis: A Naturalistic Observation

Abstract Background and Hypothesis The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia. Study Design Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29). Study Results A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits. Conclusions These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.

Violence in Relation to Cognitive Deficits and Symptom Severity in a Sample of Egyptian Patients with Schizophrenia

Abstract Background Patients with schizophrenia are significantly more likely to be violent than general population; and the consequences of this violence risk are often very serious for the patients, their caregivers and the entire community. This study assesses the risk of violence in patients with schizophrenia and its correlation with severity of symptoms and cognitive functions. Results There was a statistically significant difference between case and control groups regarding risk of violence assessed using HCR-20 scale; where 58% of the case group were found to have risk of violence compared to only 18 % in the control group, There was a significant correlation between this risk of violence and duration of untreated psychosis, no of episodes and history of substance use; also was significantly correlated with severity of symptoms assessed using PANSS and cognitive dysfunctions assessed using Wisconsin card sorting test subscales. Regarding logistic regression analysis for factors affecting violence risk; total PANSS score and history of substance use were significant independent factors that increase violence risk. Conclusions Violence risk in patient with schizophrenia is a cardinal factor that may affect life of the patients, their family and society; this risk can be affected by different factors including severity of symptoms, no of episodes, history of substance use and cognitive function of the patients as proven by the results of our study ;so our study recommends that proper comprehensive assessment of the violence risk in the routine psychiatric assessment is mandatory for rapid and better intervention.

D-serine and D-amino acid oxidase levels in patients with schizophrenia spectrum disorders in the first episode and 6-month follow-up

BackgroundD-serine and the D-amino acid oxidase (DAO) enzyme, which breaks down d-amino acids, may be involved in the pathophysiology of schizophrenia by affecting the N-methyl-D-aspartate (NMDA) receptor. The exact role of D-serine and DAO, as well as the consequences of increased DAO activity in patients with schizophrenia, remain unclear. We aimed to investigate D-serine and DAO levels in patients with first-episode schizophrenia spectrum disorders before treatment and after six months of treatment. MethodComparisons for the serum levels of D-serine and DAO were made between 81 healthy controls and 89 patients with first-episode schizophrenia spectrum disorders without a history of treatment. Further comparisons were made after 6 months for changes in these levels in the 41 patients in follow-up. The Positive and Negative Syndrome Scale (PANNS), Calgary Scale for Depression in Schizophrenia (CDSS), Montreal Cognitive Assessment Scale (MoCA), Global Assessment Scale (GAS), and Clinical Global Impression Scale (CGI) were used to evaluate the symptom severity and functionality. Secondary results included comparisons related to antipsychotic equivalent doses. ResultsBefore treatment, patients had significantly lower levels of D-serine, DAO, and D-serine/DAO ratio compared to healthy individuals (p < 0.001; p < 0.001; p = 0.004). DAO and D-serine levels of the patients were higher after six months of treatment (p = 0.025; p = 0.001). There was correlation of DAO levels with antipsychotic dosage and with PANSS negative and total subscale scores (rho = 0.421, p = 0.01; rho = 0.280, p = 0.008; rho = 0.371, p = 0.000). No correlation was found between serum D-serine level, DAO level, and the D-serine/DAO ratio with cognitive function. ConclusionsThe results suggest that D-serine and DAO may play a role that is sensitive to treatment effects in schizophrenia spectrum disorders. To gain a more comprehensive understanding of the impact antipsychotic drugs have on NMDA receptor dysfunction, there is a requirement for studies that directly evaluates the activity of the DAO enzyme.

Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation.

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.

Cariprazine as monotherapy in a case of First Episode of Psychosis (FEP)

IntroductionFirst-Episode Psychosis (FEP) is a variable condition, characterized by the emergence of new psychotic features for a period of at least 1 week. ( Marques et al.. European Psychiatry 2016; 33 S258) The treatment is antipsychotic medications, which are generally divided into two categories: first and second generation antipsychotics, and they are dopamine antagonists or dopamine partial agonists.ObjectivesThe purpose of this presentation is to assess the efficacy of monotherapy treatment with cariprazine of the First Episode of Psychosis (FEP) in a young patient.MethodsA 19-year old man was involuntarily admitted to the psychiatric intensive care unit because of aggressive and inappropriate behaviour towards his mother including threats to kill her and exhibiting his genitals. His medical history included short periods of depressed mood, as well as physical symptoms such as loss of hair and gastrointestinal symptoms, since he was 18 years old.When the patient was admitted he was cautious and anxious. During the interview he made reference to auditory hallucinations that commanded him to sexually stimulate himself in front of his mother and also persecutory delusions. Upon admission his total PANSS score was 127. The positive subscale score was 21. The patient was treated with monotherapy cariprazine, gradually increasing the dose from 1,5 mg to 6 mg per day . Furthermore, he was adjunctively treated with sertraline, gradually increasing the dose from 50 to 150 mg.ResultsAfter a period 24 days since admission the patient clinically improved and was discharged. His total PANSS score was 73 and the positive subscale was 9. He suffered no adverse effects from his treatment.ConclusionsThe use of cariprazine as a treatment for a FEP of a young male significantly improved his PANSS score after a 24-day treatment and also his disorganised behaviour. Of note, rapid tranquilization was avoided. According to the literature this is considered satisfactory response to treatment (Leucht et al. Schizophr Res. 2005; 79:231-8.). Nevertheless further investigation on the efficacy of the particular medication is necessary as its use is relatively recent in the treatment of psychosis. (Garnock et al. CNS Drugs. 2017; 31:513-525)Disclosure of InterestNone Declared

The polymorphism ZNF804A rs1344706 is differentially associated with negative symptoms domains in schizophrenia

IntroductionNegative symptoms (NS) are an important clinical characteristic of schizophrenia. In recent years, clinical research on NS has focused on their clinical heterogeneity. Based on two-factor analysis, it has been proposed to divide NS into abulia-apathy (AA) and expressive deficit (ED) domains. A number of studies have shown that these domains have different effects on the clinical features of schizophrenia, which suggests different pathophysiological mechanisms of their development. Neurobiological differences between AA and DE have been identified in neuroimaging and immunological studies but there is less research on the genetic background of NS.ObjectivesTo search for an association between the rs1344706 polymorphism of the zinc finger protein gene (ZNF804A) and the AA and ED subdomains. The rs1344706 polymorphism is one of the best-supported risk variants for schizophrenia. The risk genotype AA has been shown to be associated with clinical presentations of the disease.MethodsThe study included 1116 (741 (66.3% women) patients with schizophrenia. The diagnosis was made according to ICD-10 criteria (item F20). The average age of the patients was 38.4 (13.6) years, age at disease onset was 26.1 (10.6) years. NS were assessed with the PANSS. The PANSS-derived AA domain consisted of Emotional withdrawal (PANSS item N2), Apathetic social withdrawal (N4), Active social avoidance (G16). The DE domain included Blunted affect (N1), Poor rapport (N3), Lack of spontaneity (N6), Mannerism and posturing (G5), Motor retardation (G7), Disturbance of volition (G13). Genotyping of the ZNF804A rs1344706 polymorphism was carried out using HRM-PCR. ANOVA with genotype and sex as independent variables, and age at the time of disease manifestation and its duration as covariates was used. Post hoc tests were performed using Bonferroni correction.ResultsA significant effect of the rs1344706 polymorphism on the severity of symptoms in the AA domain was revealed (F=5.88, df=2, p=0.002). In carriers of the CC genotype, the severity of symptoms was significantly lower than in carriers of the AA genotype and the AC genotype (8.4(3.5), 9.4(7.4) and 8.8(3.5) points, respectively). This effect was independent of sex and was not mediated by age at onset or duration of disease. There was no effect of the rs1344706 polymorphism on the severity of symptoms in the ED domain.ConclusionsThe association of the ZNF804A rs1344706 (A/C) polymorphism with NS of schizophrenia has not been reported so far though some studies have found the effect of this polymorphism on PANSS positive symptoms and PANSS total score. The finding of the association with NS can be explained by the fact that the NS heterogeneity was taken into account in the present study.Disclosure of InterestNone Declared

Subgroups of patients with late onset schizophrenia-like psychoses revealed by the analysis of glutathione-dependent enzymes and inflammation markers

IntroductionWhile chronic inflammation and enhanced imbalance of pro- and antioxidant, including glutathione-dependent, systems contribute substantially to pathogenesis of mental disorders in old age, extent of oxidative stress and degree of inflammatory processes severity are varying among patients with late onset schizophrenia.ObjectivesRevealing various phenotypes in patients with late onset schizophrenia basing on measurement of activity levels for blood glutathione-dependent enzymes and inflammation markers and analysis of their links with clinical features of the patients.MethodsOf 59 studied women patients 34 were with late onset (after 40 years) and 25 with very late onset (after 60 years) schizophrenia or schizophrenia-like psychoses (F20; F22.8; F25; F23; F06.2 by ICD-10). 34 mentally healthy women elder than 50 years comprised controls. Glutathione reductase (GR), glutathione-S-transferase (GST), neutrophil elastase (NE), and α1-roteinase inhibitor (α1-PI) activities were measured in blood. PANSS, CDSS and CGI-S were used to assess the severity of psychotic symptoms, depression and treatment effectiveness.ResultsIn the whole group of patients, GR was lower (p&lt;0.05), and α1-PI was higher (p&lt;0.0001) than in control group. Clustering the patients by their biochemical and immunological signs revealed two clusters (C1, n=34, and C2, n=25) significantly differing by GST (p&lt;0.0001), NE (p&lt;0.0001), and α1-PI (p&lt;0.001) activities. As compared with controls, GST and α1-PI were higher (p&lt;0.05 and p&lt;0.0001), and NE was lower (p&lt;0.05) in C1. As compared with controls, GR activity was lower (p&lt;0.05), NE activity was higher (p&lt;0.001), and α1-PI activity was much higher (p&lt;0.001) in C2. Patients of C1 and C2 did not differ in age, diagnosis, severity of the disease, but differed in clinical features of the course of the disease: significantly more patients with very late onset schizophrenia (76%) were met in C1 (χ2=13.41, p&lt;0.001). Also, different clinical-biological correlations were found in these clusters. Particularly, negative correlations of baseline NE activity with PANSS general psychopathology subscale scores (R=-0.39, p&lt;0.05) and with total PANSS scores (R=-0.39, p&lt;0.05) were found in C1. Positive correlation of GST activity with PANSS positive subscale score was found in C2 (R=0.43, p&lt;0.05).ConclusionsThe revealed clusters differ in the extent of the glutathione antioxidant system impairment and in levels of the immune response markers. The revealing of the patient subgroups on the basis of biological markers reflecting impairments in metabolic and immune systems can represent interest in the search for individual treatment approaches.Disclosure of InterestNone Declared

Cariprazine efficacy in a 40-year untreated case of a woman with predominantly negative symptoms of psychosis: A case report

IntroductionSeveral studies have demonstrated the unfavorable and neurotoxic effects of untreated psychosis (UP) on the brain. An estimated 10 to 12 cc of brain tissue could be potentially damaged due to neuroinflammation and oxidative stress when a first episode of psychosis goes untreated. Other studies have found a correlation between the duration of untreated psychosis (DUP) and treatment resistance or nonresponse. Evidence-based schizophrenia treatment mainly relies upon the use of first and second-generation antipsychotics, without solid evidence that the former is superior to the latter regarding the treatment of negative symptoms. Both groups, however, can come with a risk of side effects. Cariprazine, a third-generation antipsychotic, represents a safe and effective treatment, targeting both the positive and negative symptoms of schizophrenia.ObjectivesTo report a clinical case of a woman with an extreme DUP with predominantly negative symptoms of schizophrenia and highlight the favorable outcome cariprazine monotherapy had on her global functioning.Methods We report a clinical case of a 58-year-old woman with a history of a 40-year UP successfully treated with 4,5mg of cariprazine. The woman was brought involuntarily for psychiatric assessment at the emergency department with a clinical image of catatonic stupor and predominantly negative symptoms of psychosis. Her total PANSS score at admission was 129. The negative subscale score was 49. She was initially treated with 3mg cariprazine and 10mg olanzapine and was gradually left on 4,5mg cariprazine monotherapy with an adjunctive 30mg mirtazapine.ResultsThe patient was dismissed after 47 days of hospitalization. Cariprazine was effective in targeting both the cognitive and affective symptoms of long-standing UP. In the long-term, cariprazine also improved remnant delusional ideas of somatic and persecutory types, enhancing the patient’s social life, ensuring her support network, and assisting her integration into the community. The patient did not report any side effects, and her blood test results were within the normal range.Conclusions Not all cases of schizophrenia are dramatic at presentation - some can have a chronic and insidious course predominated by negative symptoms. UP can lead to disastrous consequences for the patient’s biopsychosocial well-being, leading to future treatment resistance and disability. Although such cases of untreated psychosis seem to be from the past, we should be conscious of their existence and treat them with a patient-personalized and symptom-centered approach. Cariprazine was successful and effective in treating this patient with a remarkable course of UP.Disclosure of InterestNone Declared

Serum d-serine and d-amino acid oxidase (DAO) levels in schizophrenia and related psychotic disorders: a 6-month follow-up study

IntroductionD-serine and the DAO enzyme may impact the NMDA receptor and contribute to schizophrenia, but the exact role and outcomes are not fully understood due to the complexity of the disorder.ObjectivesWe analyzed serum levels of d-serine and DAO in untreated individuals with schizophrenia during acute psychotic episodes. We correlated these factors with clinical characteristics and compared results to a healthy control group. We also examined any differences after six months of treatment.MethodsThe study involved 89 patients with schizophrenia or related psychotic disorders who were hospitalized due to psychotic episodes. Also, the study had 81 healthy participants matched in terms of gender, age, and smoking status with the patient group. PANSS, CGI, GAS, CDSS, and MoCA were applied to determine the severity of the disease. Serum d-serine and DAO levels were measured by ELISA kits.ResultsDuring an acute psychotic episode, patients had significantly lower levels of D-serine, DAO, and D-serine/DAO ratio compared to healthy individuals (Z=6.52, p&lt;0.001; Z=4.54, p&lt;0.001; Z=2.90, p=0.004). Although DAO and D-serine levels increased with symptom regression after six months of treatment, the D-serine and D-serine/DAO ratios were significantly lower in patients than in healthy individuals(Z=3.52, p&lt;0.001; Z=3.44, p&lt;0,001). There was no correlation between the change in D-serine level and the change in scale scores. However, there was a negative correlation between the change in DAO level and the change in PANSS total (r=-0.681, p=0.000), anxiety scores (r=-0.336, p=0.032), and Calgary depression score (r=-0.547, p=0.000). There was a positive correlation between the change in D-serine/DAO ratio and the change in the Calgary depression scale score (r=0.353, p=0.024) in addition to PANSS positive (r=0.395, p=0.011) and total scores (r=0.585, p=0.000). Antipsychotic doses negatively correlated with the changes in DAO level (r=0.421, p=0.01). It was found that the female patients had significantly lower levels of DAO than the female healthy subjects (Z=-5.061, p&lt;0.001). No correlation was found between serum D-serine level, DAO level, and the D-serine/DAO ratio with cognitive function. D-serine level negatively correlated with age(r=-0.265, p=0.012) and age at onset of the disease (r=-0.227, p=0.032).ConclusionsThe findings support the view that D-serine and DAO may play a role in the pathophysiology of schizophrenia and related psychotic disorders. To better understand the relationship between D-serine metabolism and symptom clusters in psychosis and the effects of antipsychotic drugs on NMDAR dysfunction, further studies that directly measure DAO enzyme activity and examine cognitive symptoms in more detail are needed.Disclosure of InterestNone Declared

Different patterns of MRI structural alterations in schizophrenia spectrum disorders with delusions of influence vs persecution

IntroductionThere is strong evidence that delusions are associated with cortical and subcortical structural alterations. However, whether these abnormalities differ in different types of delusions within schizophrenia spectrum disorders remains unclear.ObjectivesWe aimed at exploring structural neural patterns underlying influence/persecutory delusions across diagnostic categories within the schizophrenia-spectrum disorders.MethodsTwenty six right-handed patients with delusional disorder (n=7) and schizophrenia (n=19), presenting with delusions were divided in two clinical subgroups. The first one was presented with persecutory delusions (n=12, 20.2-55.4 years, mean age 36.0±11.6, 2 females) and the second with delusions of influence (n=14, 21.2-47.6 years, mean age 36.7±8.4, 2 females). The control group consist of 26 matched healthy controls (20.2-53.6 years, mean age 36.3±9.9, 4 females). All participants underwent structural MRI at 3T scanner. MRI images were processed via FreeSurfer 6.0 to quantify cortical thickness (CTh) and volumes for subcortical and brainstem (midbrain, pons, superior cerebellar peduncle and medulla) structures.ResultsCompared to healthy controls, patients with delusions of influence showed decreased gray matter thickness in 17 cortical regions (Figure, A), and decreased volumes of thalamus bilaterally (left: F(1,35)=9.0, p=0.005; Cohen’s d=−0.8; right: F(1,35)=8.0, p=0.008; Cohen’s d=−0.8), left hippocampus (F(1,35)=8.8, p=0.005; Cohen’s d=−0.8), midbrain (F(1,35)=11.0, p=0.002; Cohen’s d=−0.9) and pons (F(1,35)=8.2, p=0.007; Cohen’s d=−0.8). Conversely, patients with delusions of persecution showed decreased thickness only in 4 cortical regions of the right hemisphere (figure, B) and no alterations in subcortical volumes compared to healthy controls.No differences in cortical or subcortical measures between two clinical subgroups survived corrections for multiple comparisons. No correlations between structural alterations and total PANSS or BABS scores were found in either clinical groups.Figure. Clusters of decreased cortical thickness according to atlas of Desikan et al. (2006) in delusions of influence (A) and delusions of persecution (B) subgroups compared to healthy controls.Image:Conclusions The findings suggest that patients with delusions of influence have more pronounced cortical, subcortical and brainstem structural deficit as compared to patients with delusions of persecution. However, the limited sample size and the lack of correlations with clinical scores do not allow to conclude definitely whether the revealed structural abnormalities underlies delusions of influence, which should be elucidated via further research.This study was supported by RFBR grant 21-515-12007Disclosure of InterestNone Declared

Relapse prevention with cariprazine in patients with early-stage schizophrenia

IntroductionRelapse is defined as the return of psychotic symptoms after a period of improvement/stability. Relapse is often associated with the disruptive re-hospitalization of patients. Importantly, relapse history is a strong predictor of subsequent relapses and poorer outcomes. Therefore, relapse prevention in the beginning of the disorder is especially important. Cariprazine, a novel D3-D2 partial agonist, has been effective in preventing relapse compared to placebo in stabilized patients with schizophrenia.ObjectivesTo present the efficacy of cariprazine in preventing relapse in patients with early-stage schizophrenia.MethodsPost-hoc analysis of data from a ˜96 weeks, multicentre, randomized, double-blind, placebo-controlled, parallel-group study in adults with schizophrenia. The study was composed of two parts: a 20-week open-label treatment phase and a double-blind treatment phase up to 72 weeks. During the open-label phase, patients were stabilized with cariprazine 3.0-9.0 mg/day. Then, they were randomized to continue cariprazine (fixed dosing: 3.0, 6.0, or 9.0 mg/day) or receive placebo. Relapse was defined as a deterioration of symptom scores as measured by the Positive Negative Syndrome Scale (PANSS), admission to a psychiatric hospital, exhibiting aggressive behaviour, or risk of suicide. In the present analysis, patients with a schizophrenia diagnosis history of 0-5 years were defined as early-stage patients. Baseline characteristics, and risk ratios (after the double-blind phase) with number-needed-to-treat (NNT) were calculated.ResultsOf 200 patients, 71 (35.5%) met the early-stage criteria: 32 patients in the cariprazine (CAR) and 39 in the placebo (PBO) arm. The mean age was 31.6 years in both groups with an average illness duration of 2.51+/-1.03 years in the CAR and 2.75+/-1.24 years in the PBO arm. 47% of patients in the CAR arm and 77% in the PBO arm were men. The average number of previous hospitalisations was comparable in the two groups (CAR: 2.3; PBO: 2.6), as was the severity of illness: mean PANSS Total score: 89.2 (CAR), 90.4 (PBO). Patients in both groups were highly compliant (pill-count: CAR: 98.2%; PBO: 99.5%). The main reported adverse effects were headache (CAR: 11.3%, PBO: 7.0%), insomnia (CAR: 5.6%, PBO: 4.2%), and increased triglycerides (CAR: 5.6%, PBO: 1.4%), discontinuation due to adverse event was 3.1% in the CAR and 2.6% in the PBO group. Altogether, 9.4% of patients relapsed in the cariprazine group compared to 48.7% on placebo (risk ratio=0.19 (95% confidence interval (CI): 6.3-59.2%, p=0.0041;NNT: 2.5 (95%CI: 1.7-5.1).ConclusionsIn this post-hoc analysis of patients within the first five years of schizophrenia, the relative risk of relapse was 81% reduced with cariprazine with prevention of one additional relapse after each third patient exposed to cariprazine vs placebo. Cariprazine seems to be a good treatment option for early-stage patients for preventing relapse.Disclosure of InterestC. Correll Consultant of: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellularTherapies, Jamjoom Pharma, Janssen/J&amp;J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, Vertex, and Viatris., Z. Dombi Employee of: Gedeon Richter Plc., P. Herman Employee of: Gedeon Richter Plc., Á. Barabássy Employee of: Gedeon Richter Plc.

Influencing Factors of Prepulse Inhibition Deficit in Patients with Schizophrenia and Observations on the Efficacy of Traditional Chinese Medicine

This study aims to analyze the abnormal expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with schizophrenia, investigate the influencing factors of prepulse inhibition deficit in patients and observe the efficacy of traditional Chinese medicine. A total of 106 patients with schizophrenia who underwent treatment at our hospital from January 2020 to December 2022 were included, along with 45 healthy individuals who received routine check-ups as control subjects. The significantly expressed lncRNAs were validated and analyzed using ROC curve analysis, and logistic regression analysis was used to identify the factors influencing prepulse inhibition deficit. Find 125 lncRNAs were found to be differentially expressed lncRNAs in the PBMCs of patients with schizophrenia, including 62 upregulated and 63 downregulated lncRNAs. And smoking amount, and relapse frequency were influencing factors for prepulse inhibition deficit in patients with schizophrenia. Animal experiments were conducted using hematoxylin eosin staining to observe the number and morphology of neurons in the hippocampal CA3 area and prefrontal cortex of rats, and the effects of natural Chinese medicine Poria cocos on the nervous system were analyzed. Find the acidic polysaccharides from Poria cocos, a natural traditional Chinese medicine, can promote the regeneration of neuronal cells, reduce excessive autophagy of neurons in the CA3 area of the hippocampus and prefrontal cortex of rats, promote neuronal cell proliferation, and improve neuronal cell morphology. Traditional Chinese medicine has good effects in psychopathology, positive and negative symptoms, and PANSS total score. Disruption of lncRNA expression may be one of the biological factors contributing to the pathogenesis of schizophrenia and is closely related to its mechanism. Prepulse inhibition, reflecting sensory gating function, is an important factor affecting perceptual and cognitive functions in patients with schizophrenia. Gender, smoking amount, and relapse frequency may influence prepulse inhibition deficit in these patients. Traditional Chinese medicine shows potential in improving prepulse inhibition deficit. The acidic polysaccharides from Poria cocos, a natural traditional Chinese medicine, can promote the regeneration of neuronal cells, effectively improve the damage to the structure and function of neurons in the hippocampal CA3 area and prefrontal cortex. When used in combination with other traditional Chinese medicines, it could offer new approaches for treating schizophrenia.

Evaluation of the Relationship between Disability and Disease Severity, Cognitive Functions, and Insight in Patients with Schizophrenia.

: This study aims to examine the clinical characteristics, cognitive functions, and levels of insight, which are thought to be related to disability in schizophrenia patients, and to determine which variable will guide the clinician to predict the disability. : Participants were 102 individuals with schizophrenia aged 18-60. All participants completed the social functioning scale and the Beck cognitive insight scale. To determine the severity of disability, World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale was conducted. Positive and negative syndrome scale, Calgary depression scale for schizophrenia, trail making tests and Stroop test were performed. : The regression analysis indicated that high income, increased education level, and fewer hospitalization variables had significant negative effects (p ＜ 0.05) on the WHODAS overall score, explaining 20.8% of the variance. The duration of trail-making test form A, PANSS total score, and Stroop 3 duration variables had significant positive effects (p ＜ 0.05) on the WHODAS score, explaining 49.3% of the total variance. Increased levels of education, higher income, and higher cognitive insight were found to be associated with less disability. Increased severity of disease and some deterioration in the mental field were found to be related to high disability. : In this research, the predictors of disability in individuals with schizophrenia, level of education, and income are among the predictors of disability, and disease severity seems to be more related to the impairment of cognitive functions. Interventions and treatments that support the psychosocial functionality should be planned rather than symptom-oriented treatment approaches.

The neutrophil-to-Lymphocyte ratio is associated with clinical symptoms in first-episode medication-naïve patients with schizophrenia

Innate immunity has been shown to be associated with schizophrenia (Sch). This study explored the relationship between symptoms and neutrophil-to-lymphocyte ratio (NLR) (a marker of innate immunity) in patients with Sch. Ninety-seven first-episode medication-naïve (FEMN) patients with Sch and 65 healthy controls were recruited in this study. We measured the complete blood count and assessed the clinical symptoms using the PANSS scales. We found higher NEU counts and NLR in patients with Sch compared with control subjects. Male patients showed a higher NEU count than female patients. In addition, FEMN patients with higher NLR and NEU values showed higher PANSS-p, PANSS-g, and PANSS-total scores (all p < 0.05). Regression analysis revealed that NLR was a predictor for PANSS total scores in patients with Sch. Higher NLR value was observed in patients with Sch and the significant associations between NLR and psychotic symptoms indicate that an imbalance in inflammation and innate immune system may be involved in the pathophysiology of Sch.

Population Pharmacodynamic Models of Risperidone on PANSS Total Scores and Prolactin Levels in Schizophrenia.

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.

A randomized, prospective, active-controlled study comparing intramuscular long-acting paliperidone palmitate versus oral antipsychotics in patients with schizophrenia at risk of violent behavior

ObjectivePaliperidone palmitate (PP) is an effective long-acting antipsychotic injection, but its impact on the behavior of schizophrenia patients with dangerous tendencies requires further investigation. This study aims to explore the effects of long-term antipsychotic treatment on this population in the community. MethodsThis 49-week, randomized controlled trial was conducted across 21 communities in Wuhan and enrolled 134 schizophrenia patients at risk for violent behavior. With a fixed block size of 10, participants were randomly assigned to receive either intramuscular PP 1-month formulation (PP1M) or oral antipsychotic medication (OAP) at a 1:1 ratio. Changes in patients' risk for violent/aggressive behavior, family burden, social, and cognitive functioning were measured using VRAPP, MOAS, PANSS, FBS, PSP, and RBANS scales from baseline to endpoint. Longitudinal data from multiple repeated measures were analyzed using linear mixed-effects models. ResultsThe study protocol was completed by 77.6% of the patients overall. Significant improvements were observed in the risk assessment scores, MOAS total score, PANSS total score, PSP total score, and FBS total score of patients in the PP1M group from baseline to the end of treatment (all P < 0.05). Importantly, compared to patients in the OAP group, the improvements in these measures were also significantly greater in the PP1M group. Commonly observed AEs, such as hyperprolactinemia (70.3% vs. 62.65%) and muscle tension (45.3% vs. 57.8%), were considered to be the PP-related AEs. Nonetheless, the differences between the two groups did not reach statistical significance, and no new safety concerns emerged. ConclusionsOur study suggests that PP long-acting injection (LAI) is a safe and effective treatment option for community-dwelling schizophrenia patients with impulsive violence and risky behaviors.

Selected neuroendocrine factors as potential molecular biomarkers of early non-affective psychosis course in relation to treatment outcome: A pilot study

The aim of this pilot study was to find whether the dysregulation of neuroendocrine biomarker signaling pathways in the first episode of non-affective psychosis is a predictive factor of treatment outcome. Patients with the first episode of non-affective psychosis (N = 29) were examined at admission, at discharge, and at follow-up (N = 23). The biomarkers included serum aldosterone, cortisol, free thyroxine, thyroid stimulating hormone, and prolactin. We revealed lower baseline aldosterone and higher baseline cortisol concentrations in patients with very good outcome compared to those with good outcome after one year. We failed to reveal any significant association between treatment outcome and neurohumoral biomarkers in the whole sample at 1-year follow-up. However, baseline aldosterone concentrations negatively correlated with total PANSS scores at the discharge. Lower baseline aldosterone and higher baseline cortisol concentrations have the potential to predict a more favorable outcome for patients with the first episode of psychosis.