Acute Schizophrenia Research Articles

Exploring peptide dendrimers for intestinal lymphatic targeting: formulation and evaluation of peptide dendrimer conjugated liposomes for enhancing the oral bioavailability of Asenapine maleate.

Asenapine maleate (ASPM) is a second-generation atypical antipsychotic that is approved for treating acute schizophrenia and bipolar disorder in adults by the US FDA. The major downside of ASPM therapy is rapid, extensive first-pass hepatic metabolism following its oral administration with a very low oral bioavailability of < 2%. In this work, we developed ASPM nanoformulations conjugated with ligands such as arginine-glycine-aspartic acid (RGD) and peptide dendrimers (PDs) with the intention of improving the oral bioavailability of the drug by targeting it to the intestinal lymphatic system (ILS). Peptide dendrimers (PDs), both lipidated and nonlipidated, were synthesized by Fmoc solid phase peptide synthesis (SPPS). Reverse phase high performance chromatography (RP-HPLC) was used to purify the synthesized PDs, and the PDs were characterized by differential scanning calorimetry (DSC) electrospray ionization mass spectroscopy (ESI+-MS), Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The thin film hydration method was used to prepare liposomes, and the process variables affecting the liposome parameters were optimized using the Box‒Behnken design (BBD).Liposomes were PEGylated using DSPE-PEG-COOH2000 and further conjugated with ligands (RGD, PD-1 and PD-2) using EDC-NHS chemistry. The formulation was characterized using different spectroscopic techniques. In vitro, cell line studies, such as cytotoxicity, cell uptake, uptake mechanism, and receptor saturation studies, were performed on both Caco2 and Raji-B cells. The pharmacokinetic parameters of the developed liposomal formulation were evaluated using pharmacokinetic studies on Sprague- Dawley (SD) rats. The psychostimulant-induced hyperactivity model was used to evaluate the pharmacodynamic performance of the developed formulations by measuring the reversal of hyperlocomotor activity induced by levodopa-carbidopa.

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.

Psychotic Arousal and the Psychopathology of Acute Schizophrenia: An Exploratory Study of the Experiential Emotional State in Acute Psychosis.

Background: Increasing research data suggest that the dysfunction of emotional brain systems may be an important contributor to the pathophysiology of schizophrenia. However, contemporary psychopathology consistently underestimates the role of emotions in the phenomenology of the disease. Psychotic arousal (PA) is a conceptually defined psychopathological construct aiming to portray the experiential emotional state of acute psychosis. The concept provides an explanatory model for the emergence of psychosis, and the formation and maintenance of delusions based on neurobiological models on the formation of core consciousness and subjectivity. This is the first exploratory study of the major assumptions, endorsed in the project summarized as follows: (1) psychotic arousal is a discrete state, eligible for investigation; (2) abnormal experiential feelings are an integral part of this state; and (3) the state is responsive to antipsychotic intervention during the first weeks of treatment. Methods: We developed the Psychotic Arousal Scale (PAS) accordingly, explored its first psychometric properties and tested its relation to other psychopathological measures. Fifty-five acute schizophrenia patients were evaluated with the PAS, the Positive and Negative Syndrome Scale, the Brown Assessment of Beliefs Scale, the Hamilton Anxiety Scale, and the Calgary Depression Scale. Cronbach α coefficients, t-test analysis, correlations and mixed linear regression models were applied for testing the internal reliability of the scale, associations between parameters and sensitivity to change in three time periods during therapeutic intervention. Results: The results of the study support that (PA) is eligible for investigation as a discrete psychopathological state. Abnormal experiential feelings are an integral part of this state, presenting high affinity with other affective measures; their degree of severity relates to the delusions' conviction and are amenable to antipsychotics early in treatment during the acute psychotic episode. Conclusions: The findings of this exploratory study are connotative of the presence of an emotional arousal permeated by abnormal experiential feelings during acute psychosis, largely overlooked by contemporary psychopathology.

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials

BackgroundCurrently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M1 /M4 preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms. MethodsData were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample N = 640). PANSS criteria proposed in the literature identified a subset of study participants (n = 64) with prominent NS. ResultsKarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (p < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility. ConclusionsParticipants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.

THE RELATIONSHIP BETWEEN COGNITIVE DEFICITS AND CLINICAL CHARACTERISTICS IN PATIENTS WITH SCHIZOPHRENIA

Introduction: Schizophrenia is an endogenous psychotic disorder with a chronic course, which is characterized by dysfunction in multiple domains: perceptions, thinking, emotions, and cognition. Objective: The main aim of the study was to introduce the relationship between clinical characteristics and cognitive deficits in patients with schizophrenia. Methods: The research involved 53 randomly selected male and female respondents from 18 to 60 years of age, who suffer from schizophrenia according to the diagnostic criteria of the International Classification of Diseases – ICD 10, acute schizophrenia treated in the Psychiatric Hospital Skopje - Skopje. We used the following measuring instruments: the Positive and Negative Syndrome Scale (PANSS) and the Schizophrenia Cognition Rating Scale (SCoRS). Results: The results indicated that the acute schizophrenic patients had higher rating scores in the SCoRS assessment (M=45.736, SD=8.908) in the first week after psychosis onset. A high degree of positive and negative symptoms was a strong predictor of higher cognitive deficits in patients with schizophrenia. A positive relationship was observed between the PANSS-Positive and ScoRS level (F (53) =0.559, sig. =.001, p&lt;.01). At the same time, positive relationship was observed between the PANSS-Negative and ScoRS level (F (53) =0.283 sig. =.001, p&lt;.01). Conclusions: In the course of our longitudinal prospective study, we found that clinical characteristics of schizophrenia had a great impact on the cognitive dysfunction, whereby this is evident in the acute stage of the disease.

Aberrant salience in acute versus chronic schizophrenia: Do medication and positive symptoms make a difference?

The nature of aberrant salience in schizophrenia, whether it is a state or a trait phenomenon, remains unclear. To assess and compare aberrant salience in patients with schizophrenia at different stages of the illness and to explore its association with symptom severity and medication use. A total of 113 subjects were included, comprising 83 patients with schizophrenia divided into three groups: group A (acute drug-free symptomatic stage, n = 23), group B (chronic-medicated symptomatic stage, n = 30), and group C (chronic-medicated asymptomatic stage, n = 30). These were compared with a healthy control group (group D, n = 30). Participants were assessed using the Aberrant Salience Inventory (ASI) and clinical rating scales, including Psychotic Symptom Rating Scales, Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms (SANS). Significant differences were observed across almost all domains of aberrant salience. The most notable differences were between the symptomatic groups (A, B) and the healthy controls (D). Subgroup analysis showed no significant differences between the acute (A) and chronic groups (B, C), but significant differences were found between the symptomatic (A, B) and asymptomatic (C) groups in several domains and in the total ASI score. A highly significant positive correlation was noted between the total ASI score and the symptom rating scales, except for SANS. Aberrant salience is significantly elevated in patients with prominent positive symptoms, particularly delusions and hallucinations. It appears comparable to the general population in chronic remitted patients, suggesting that aberrant salience is state-dependent. Medication did not significantly influence aberrant salience as both medicated and nonmedicated symptomatic patients continued to exhibit it. However, medication may contribute to reducing aberrant salience by alleviating positive psychotic symptoms.

Dose-dependent effects of oral cannabidiol and delta-9-tetrahydrocannabinol on serum anandamide and related N-acylethanolamines in healthy volunteers

BackgroundThe mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual’s effective dosage. In schizophrenia, alterations in anandamide (AEA)...

Immune-based Machine learning Prediction of Diagnosis and Illness State in Schizophrenia and Bipolar Disorder

BackgroundSchizophrenia and bipolar disorder frequently face significant delay in diagnosis, leading to being missed or misdiagnosed in early stages. Both disorders have also been associated with trait and state immune abnormalities. Recent machine learning-based studies have shown encouraging results using diagnostic biomarkers in predictive models, but few have focused on immune-based markers. Our main objective was to develop supervised machine learning models to predict diagnosis and illness state in schizophrenia and bipolar disorder using only a panel of peripheral kynurenine metabolites and cytokines. MethodsThe cross-sectional I-GIVE cohort included hospitalized acute bipolar patients (n = 205), stable bipolar outpatients (n = 116), hospitalized acute schizophrenia patients (n = 111), stable schizophrenia outpatients (n = 75) and healthy controls (n = 185). Serum kynurenine metabolites, namely tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinaldic acid (QUINA), xanthurenic acid (XA), quinolinic acid (QUINO) and picolinic acid (PICO) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), while V-plex Human Cytokine Assays were used to measure cytokines (interleukin-6 (IL-6), IL-8, IL-17, IL-12/IL23-P40, tumor necrosis factor-alpha (TNF-ɑ), interferon-gamma (IFN-γ)). Supervised machine learning models were performed using JMP Pro 17.0.0. We compared a primary analysis using nested cross-validation to a split set as sensitivity analysis. Post-hoc, we re-ran the models using only the significant features to obtain the key markers. ResultsThe models yielded a good Area Under the Curve (AUC) (0.804, Positive Prediction Value (PPV) = 86.95; Negative Prediction Value (NPV) = 54.61) for distinguishing all patients from controls. This implies that a positive test is highly accurate in identifying the patients, but a negative test is inconclusive. Both schizophrenia patients and bipolar patients could each be separated from controls with a good accuracy (SCZ AUC 0.824; BD AUC 0.802). Overall, increased levels of IL-6, TNF-ɑ and PICO and decreased levels of IFN-γ and QUINO were predictive for an individual being classified as a patient. Classification of acute versus stable patients reached a fair AUC of 0.713. The differentiation between schizophrenia and bipolar disorder yielded a poor AUC of 0.627. ConclusionsThis study highlights the potential of using immune-based measures to build predictive classification models in schizophrenia and bipolar disorder, with IL-6, TNF-ɑ, IFN-γ, QUINO and PICO as key candidates. While machine learning models successfully distinguished schizophrenia and bipolar disorder from controls, the challenges in differentiating schizophrenic from bipolar patients likely reflect shared immunological pathways by the both disorders and confounding by a larger state-specific effect. Larger multi-centric studies and multi-domain models are needed to enhance reliability and translation into clinic.

Assessment of resting cerebral perfusion between methamphetamine-associated psychosis and schizophrenia through arterial spin labeling MRI.

The clinical manifestations of methamphetamine (METH)-associated psychosis (MAP) and acute paranoid schizophrenia (SCZ) are similar. This study aims to assess regional cerebral blood flow (rCBF) in individuals who use METH and in those with SCZ using the MRI arterial spin labeling (ASL) technique. We prospectively recruited 68 participants and divided them into four groups: MAP (N = 15), SCZ (N = 13), METH users with no psychosis (MNP; N = 22), and normal healthy controls (CRL; N = 18). We measured rCBF using an MRI three-dimensional pseudo-continuous ASL sequence. Clinical variables were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS). Group-level rCBF differences were analyzed using a two-sample t-test. Decreased rCBF was found in the precuneus, premotor cortex, caudate nucleus, dorsolateral prefrontal cortex, and thalamus in the MNP group compared with the CRL group. The MAP group had significantly decreased rCBF in the precuneus, hippocampus, anterior insula, inferior temporal gyrus, inferior orbitofrontal gyrus, and superior occipital gyrus compared with the MNP group. Increased rCBF in the precuneus and premotor cortex was seen in the MAP group compared with the SCZ group. rCBF in the precuneus and premotor cortex significantly correlated negatively with the PANSS but correlated positively with BACS scores in the MAP and SCZ groups. METH exposure was associated with decreased rCBF in the precuneus and premotor cortex. Patients with MAP exhibited higher rCBF than those with SCZ, implying preserved insight and favorable outcomes. rCBF can therefore potentially serve as a diagnostic approach to differentiate patients with MAP from those with SCZ.

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.

Bartonella species bacteremia in association with adult psychosis.

The potential role of pathogens, particularly vector-transmitted infectious agents, as a cause of psychosis has not been intensively investigated. We have reported a potential link between Bartonella spp. bacteremia and neuropsychiatric symptoms, including pediatric acute onset neuropsychiatric syndrome and schizophrenia. The purpose of this study was to further assess whether Bartonella spp. exposure or infection are associated with psychosis. In a blinded manner, we assessed the presence of anti-Bartonella antibodies by indirect immunofluorescence assays (IFA), and infection by amplification of bacterial DNA from blood by quantitative polymerase chain reaction (qPCR), digital PCR (dPCR), and droplet digital PCR (ddPCR) in 116 participants. Participants were categorized into one of five groups: 1) controls unaffected by psychosis (n = 29); 2) prodromal participants (n = 16); 3) children or adolescents with psychosis (n = 7); 4) adults with psychosis (n = 44); and 5) relatives of a participant with psychosis (n = 20). There was no significant difference in Bartonella spp. IFA seroreactivity between adults with psychosis and adult controls unaffected by psychosis. There was a higher proportion of adults with psychosis who had Bartonella spp. DNA in the bloodstream (43.2%) compared to adult controls unaffected by psychosis (14.3%, p = 0.021). The Bartonella species was determined for 18 of the 31 bacteremic participants, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. berkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18). In conjunction with other recent research, the results of this study provide justification for a large national or international multi-center study to determine if Bartonella spp. bacteremia is more prevalent in adults with psychosis compared to adults unaffected by psychosis. Expanding the investigation to include a range of vector-borne and other microbial infections with potential CNS effects would enhance knowledge on the relationship between psychosis and infection.

LC-MS/MS quantification of olanzapine in hair after alkaline digestion.

Olanzapine (OLZ), a second-generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC-MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1-100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug-positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after "digestion" with comparative parameters prior to chromatographic analysis.

412. Efficacy of Karxt on Negative Symptoms in Acute Schizophrenia: A Post Hoc Analysis of Participants With Prominent Negative Symptoms

412. Efficacy of Karxt on Negative Symptoms in Acute Schizophrenia: A Post Hoc Analysis of Participants With Prominent Negative Symptoms

570 Adult Self-Inflicted Burn Demographics in West Texas

Abstract Introduction Self-inflicted burns (SIB) are a subset of burns defined based on self-injury, sometimes also referred to as self-immolation. The United States generally reports SIB in the context of psychiatric ailment. However, due to the difference in geographic locations, the West Texas burn coverage has never been checked for SIB patients. We hypothesize that patients with SIB have higher rates of psychiatric disorders and are generally older men. Methods We obtained a list of all patients admitted to the burn intensive care unit (BICU) with a Second/Third-degree burn. After, we verified the inclusion of patients meeting the study criteria from July 01, 2011, to July 01, 2021, ages between 18 and 89, and a completed Lund-Browder Chart. Data was collected from a mix of manual chart review from electronic health records and electronic data retrieval. Patients were split into two groups, SIB and non-intentional burns (NIB). Bivariate analysis was conducted using Mann Whitney U test and either Fisher’s exact test or Chi-square test when independent variables were categorical. Results The initial data set (n=2,875) decreased due to missing burn documentation, burn intensive care unit admission, and incomplete records and was split into two groups: SIB (n=49) and NIB (n=1,243). The average age and percentage of male patients compared between NIB and SIB were not significant (p=0.32, p=0.39). However, TBSA, frequency of inhalation injury, burn symmetry, suicidal ideation, history of drug abuse, history of self-harm, history of mental illness, past mental health hospitalization, and mortality were all significantly higher in the SIB group (p&amp;lt; 0.001). There was also a statistically significant higher frequency of psychological disorders in the SIB group for depression, acute schizophrenia, borderline personality disorder, bipolar disorder (p&amp;gt;0.001), anxiety disorders (p=0.02), post-traumatic stress disorder (p=0.006), atypical psychosis, drug-induced psychosis, and delirium (p=0.04). Conclusions The demographics of the West Texas SIB population are comparable to that of the United States, predominantly older male patients. Similarly, many psychiatric disorders occur at a higher frequency in SIB patients than NIB: depression, acute schizophrenia, borderline personality disorder, anxiety disorder, post—traumatic stress disorder, bipolar disorder, atypical psychosis, drug-induced psychosis, and delirium. Applicability of Research to Practice While SIB patients make a small portion of the total burn population, there burns are often associated with worse outcomes – mortality, larger burns, and length of stay. The severity of their injuries begs the need for further analysis and hopefully prevention of SIB. Addressing psychiatric facilities and preventing these incidents from occurring may offer preventative methods.

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data.

Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. PROSPERO-ID: CRD42023451628.

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

Unconjugated bilirubin as a state marker in patients with schizophrenia in acute episode: an Egyptian study

BackgroundThere is a substantial body of evidence linking unconjugated bilirubin to schizophrenia. Most of the earlier research has found a statistically significant relationship between the two factors.Aim of the workTo study the level of unconjugated bilirubin in individuals with acute schizophrenia and to investigate its correlation with neuropsychological, psychopathological, and psychosocial aspects of the disorder.Patients and methodsEighty schizophrenia patients were included in the sample, they had multiple previous episodes and were in acute episodes at the time of recruitment. Forty healthy individuals were recruited for the control group. The DSM-IV was used to diagnose the subjects, and the Trail Making Test (TMT), Positive and Negative Syndrome Scale (PANSS), General Assessment of Function (GAF), and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) were used to evaluate the subjects’ social functioning, symptom severity, and cognitive functioning. A blood sample was drawn to measure serum bilirubin level. We analyzed the relationship and correlation of unconjugated bilirubin with the previous scale scores.ResultsCompared to healthy control individuals, who volunteered to participate, schizophrenia patients reported significantly higher levels of both total and indirect bilirubin. One subject (with schizophrenia) had an abnormally elevated total bilirubin level (> 1.2 mg/dL). Neither the direct nor the indirect bilirubin levels (> 0.3 mg/dl or > 1.2 mg/dL) were clinically abnormal in any of the patients. PANSS total score, PANSS N score, and PANSS G score were found to have a statistically significant positive connection with levels of total, direct, and indirect bilirubin. Age, gender, smoking, BMI, Total PANSS, PANSS P, PANSS N, PANSS G, GAF, TMT-A, TMT-B, antipsychotic medication, psychotic disorder duration, and duration of untreated psychosis were not predictive of total or indirect bilirubin levels, according to linear regression analysis. However, Total PANSS, PANSS N, and PANSS G were significantly predictive for direct bilirubin levels.ConclusionA statistically significant difference in total and unconjugated bilirubin mean serum levels between schizophrenia patients and healthy individuals was found. More studies are recommended to revise the contradictory results in literature on the unconjugated bilirubin and Schizophrenia.

NADPH-dependent peroxidase activity of antibodies in patients with schizophrenia

IntroductionThe development of oxidative stress in patients with schizophrenia is associated with changes in the level of activity of antioxidant enzymes. It is likely that catalytically active antibodies (abzymes) can take on these functions. Abzymes are antibodies with enzymatic activity. Catalase and SOD activity of abzymes was previously detected in patients with schizophrenia. But NADPH-dependent peroxidase activity has not been studied. The present work discusses the protective role of abzymes against reactive oxygen species within the pathogenesis of schizophrenia.ObjectivesThe aim of the study was to investigate the NADPH-dependent peroxidase activity of IgG in patients with paranoid schizophrenia in the exacerbation phase and in the remission phase.MethodsA total of 124 patients were examined during the work. Of them, 82 patients with paranoid schizophrenia (F20.0) had a mean age of 33.6±5.12 years (52 males, 30 females), disease duration averaged 8.9± 4.62 years. Patients with schizophrenia included 42 patients with acute schizophrenia and 40 patients with schizophrenia in therapeutic remission. The control group included 42 sex- and age-matched patients. IgG was purified by affinity chromatography on columns with proteinsepharose on an AKTA purifier chromatograph (GE). The homogeneity of isolated IgG preparations was checked by Lemilly electrophoresis in a gradient of 4-18% PAAG. Gel filtration under pH-shock conditions was performed on a Superdex-200 HR 10/30 column. NADPH-dependent peroxidase activity of IgG was determined on a SPECORD M-40 spectrophotometer (Carl Zeiss) at 340 nm by NADPH oxidation in the conjugated glutathione reductase reaction of tertiary butyl hydroperoxide reduction. Statistical processing of data was performed in Statistica 12.0 program.ResultsIt was proved that IgG from patients with schizophrenia had NADPH-dependent peroxidase activity, and this activity is an intrinsic property of the investigated antibodies. The NADPH-dependent peroxidase activity in IgG patients in the exacerbation stage was increased 3-fold (p=0.0001) compared to the studied activity in the group of healthy individuals, and it was increased 2-fold (p=0.017) in the group of patients in therapeutic remission compared to the activity in healthy individuals. Also NADPH-dependent IgG peroxidase activity in patients in remission was 1.7 times lower than in patients during the exacerbation period (p=0.012).ConclusionsIt was established for the first time that abzymes from patients with schizophrenia and healthy individuals have NADPH-dependent peroxidase activity and can decompose lipo and hydroperoxides. We hypothesize that these abzymes help cope with generalized oxidative stress. Under the influence of neuroleptic therapy in patients in remission, the level of oxidative stress and NADPH-dependent peroxidase activity of abzymes decrease.Disclosure of InterestNone Declared

The activity of platelet enzymes and subpopulation composition of monocytes in schizophrenia

IntroductionThe studies on various groups of patients with schizophrenia revealed impairments in immune system, glutamatergic, and antioxidant systems contributing substantially in schizophrenia pathogenesis.Objectives To search for links between the activities of platelet enzymes involved in glutamate and glutathione metabolism and monocytes’ subpopulation compositions in patients with schizophrenia and to identify possible correlations of the biomarkers with clinical data. Research objectives: determination of subpopulation ratio of monocytes; measurement of the activity levels of glutamate dehydrogenase (GDH), phosphate-activated glutaminase (PAG), glutathione reductase (GR) and glutathione S-transferase (GST) in blood platelets; search for correlations between these parameters and the scores by psychometric scales.Methods The study included 36 women aged 16-45 years with acute schizophrenia hospitalized in the Mental Health Research Centre with their current condition assessed as depressive-delusional. The control group consisted of 17 women 18-45 years old without somatic or mental pathology. GDH, PAG, GR and GST activities were measured by spectrophotometric methods, and numbers of monocyte subpopulations - “classical”, “intermediate”, “non-classical” - by flow cytometry. The Hamilton Depression Rating Scale (HAMD-17) was used to assess depression severity. The data was processed using the Statistica 8.0 software.Results The detected changes in monocyte subpopulations’ composition towards the increase in the proportion of cells having a pro-inflammatory phenotype (CD14++CD16+ “intermediate”) indicated the activation of inflammatory reactions. Also, the activities of platelet enzymes of glutathione metabolism (GR and GST) were significantly decreased (p&lt;0.05). Moreover, GDH and GST activities significantly correlated with the scores by HAMD-17 (r=0.40, p=0.022 and r=0.45, p=0.030, respectively). The results indicate the presence of pathological inflammatory process, the decrease in activities of glutathione antioxidant metabolism enzymes and a link to glutamate metabolism involvement (GDH) in the studied patient group.Conclusions The identified redistribution in the monocyte subpopulations’ composition and decrease in the activity of enzymes involved in glutamate metabolism and antioxidant system indicate the involvement of the immune, glutamate and antioxidant systems in the pathogenesis of schizophrenia and may reflect a functional interaction between these systems.Disclosure of InterestNone Declared

Pathophysiology and Management of Amphetamine-Related Psychiatric Disorders

IntroductionAmphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis.ObjectivesThe objectives of this e-poster is to identify the pathophysiology of amphetamine-related psychiatric disorders and outline the available treatment and management options for amphetamine-related psychiatric disorders.MethodsA bibliopgraphical review was performed using PubMed platform. All relevant articles were found using the keywords: psychotic episode, amphetamines, pathophysiology and menagement.Results Amphetamines inhibit monoamine (dopamine, norepinephrine, epinephrine, serotonin) reuptake, leading to increased monoamine concentrations in the neuronal synapse. Amphetamines can also lead to increased monoamines in the cytosol by interactions with vesicular monoamine transporter 2. Dopamine and norepinephrine release in the nucleus accumbens results in a feeling of euphoria and a reward feedback loop, which may result in addiction. Studies also suggest increased dopaminergic pathways lead to glutamate excesses in the cerebral cortex, altering the function of cortical GABAergic neurons. This damage leads to dysregulation of glutamate in the cerebral cortex, a precursor to psychosis. Prior psychiatric studies have found that GABAergic cortical dysfunction seems to relate to schizophrenia. Generally, acutely agitated psychotic patients are treated with intravenous benzodiazepines (lorazepam, diazepam, or midazolam) as first-line agents. However, if a second-line agent is needed, antipsychotic medicines like risperidone, haloperidol, ziprasidone, and olanzapine have been successful in managing amphetamine-associated psychosis. Lipophilic beta-blockers, such as metoprolol and labetalol, have also been used successfully to resolve agitation and hyperadrenergic vital signs.ConclusionsCompared to schizophrenic psychosis, amphetamine-induced acute psychosis induced appears to demonstrate a more rapid recovery. It also seems to resolve with substance abstinence; however, this recovery may be incomplete.Disclosure of InterestNone Declared