Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia.

OBJECTIVE: This trial analyzed high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), and macrophage migration inhibitory factor (MIF) level in serum and their correlation with symptom severity and cognitive function in patients with schizophrenia (SP). METHODS: Sixty-eight SP patients were enrolled in the SP group, and 68 healthy volunteers were in the control (CN) group. Serum hs-CRP, Hcy, and MIF were measured, and symptom severity was assessed with the Positive and Negative Symptom Scale (PANSS). Cognitive function was determined with the MATRICS Consensus Cognitive Battery (MCCB). The SP group was divided into high PANSS score (PANSS ≥70 points) and low PANSS score (PANSS <70 points), or the mild cognitive dysfunction group and severe cognitive dysfunction group according to the median MCCB score. The correlation between serum hs-CRP, Hcy, and MIF levels and PANSS and MCCB scores in SP patients was examined by Pearson correlation analysis. RESULTS: SP patients had higher serum hs-CRP, Hcy, and MIF levels and showed higher PANSS scores and lower MCCB total score. Serum hs-CRP, Hcy, and MIF levels in the high PANSS group were higher than those in the low PANSS group and in the severe cognitive dysfunction group than in the mild cognitive dysfunction group. Serum hs-CRP, Hcy, and MIF levels in SP patients were positively correlated with PANSS total score and negatively correlated with MCCB total score. CONCLUSION: High serum hs-CRP, Hcy, and MIF levels in SP patients are correlated with symptom severity and cognitive dysfunction.

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

BACKGROUND: Sleep 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. METHODS: Plasma 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. RESULTS: 16 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. CONCLUSIONS: Our 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.

[IPA's clinical expertise in the identification and assessment of somatic pain in schizophrenic patients]. / Expertise clinique de l'IPA PSM dans le repérage et l'évaluation de la douleur somatique chez les personnes schizophrènes.

Identifying and assessing somatic pain in people with schizophrenia remains a major public health issue for this vulnerable population. In France, Advanced Practice Nursing is developing, based on a practice built around clinical expertise. How can the clinical expertise of psychiatric and mental health APNs improve the identification and assessment of somatic pain in these patients, and thus help to improve their somatic health?

[Clinical and psychometric characteristics of cognitive and negative disorders in schizophrenia]. / Klinicheskie i psikhometricheskie osobennosti kognitivnykh i negativnykh rasstroistv pri shizofrenii.

OBJECTIVE: To establish the characteristics of clinical manifestations and cognitive tests in patients with schizophrenia, with a predominance of cognitive and negative disorders. MATERIAL AND METHODS: We examined 76 patients, 66 in the main group, 10 in the comparison group, who were treated in Psychiatric Hospital No. 1 and Psychiatric Hospital No. 4 (Moscow). Clinical-psychopathological, psychometric and statistical methods were used. Features of cognitive functioning were studied using the Frontal Assessment Battery (FAB) and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS). Emotional intelligence scores were assessed using the Ekman Face Emotion Recognition (EFER) test. RESULTS: Patients with schizophrenia showed dominance of one of 3 types of deficit symptoms: cognitive, emotional, and volitional. Cognitive functions were significantly reduced in patients with schizophrenia when compared with the comparison group (mean FAB score (M±SD) 13.44±2.97 in patients with schizophrenia vs. 16.10±1.70 in the comparison group; t=4.10; p<0.001). Cognitive functions were particularly reduced in patients with volitional deficit (mean EFER total score 42.40±9.0 in patients with volitional deficit vs. 47.21±633 in patients with cognitive deficit; t=2.12; p=0.039; mean FAB score 12.83±3.29 in patients with volitional deficit vs. 16.10±1.70 in the comparison group; t=4.24; p<0.001; mean ECAS score specific to ALS 78.80±9.07 in patients with volitional deficit vs. 84.50±6.71 in the comparison group; t=2.18; p=0.034). CONCLUSION: The greatest contribution to the development of cognitive disorders in schizophrenia is made by dysfunction of frontal (especially) and temporal cortex. Executive functions, speech skills and verbal fluency are most severely damaged.

Cerebellar dysconnectivity in schizophrenia and bipolar disorder is associated with cognitive and clinical variables.

BACKGROUND: Abnormal cerebellar functional connectivity (FC) has been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). However, the patterns of cerebellar dysconnectivity in these two disorders and their association with cognitive functioning and clinical symptoms have not been fully clarified. In this study, we examined cerebellar FC alterations in SCZ and BD-I and their association with cognition and psychotic symptoms. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 39 SCZ, 43 BD-I, and 61 healthy controls from the Consortium for Neuropsychiatric Phenomics dataset were examined. The cerebellum was parcellated into ten functional networks, and seed-based FC was calculated for each cerebellar system. Principal component analyses were used to reduce the dimensionality of the diagnosis-related FC and cognitive variables. Multiple regression analyses were used to assess the relationship between FC and cognitive and clinical data. RESULTS: We observed decreased cerebellar FC with the frontal, temporal, occipital, and thalamic areas in individuals with SCZ, and a more widespread decrease in cerebellar FC in individuals with BD-I, involving the frontal, cingulate, parietal, temporal, occipital, and thalamic regions. SCZ had increased within-cerebellum and cerebellar frontal FC compared to BD-I. In BD-I, memory and verbal learning performances, which were higher compared to SCZ, showed a greater interaction with cerebellar FC patterns. Additionally, patterns of increased cortico-cerebellar FC were marginally associated with positive symptoms in patients. CONCLUSIONS: Our findings suggest that shared and distinct patterns of cortico-cerebellar dysconnectivity in SCZ and BD-I could underlie cognitive impairments and psychotic symptoms in these disorders.

The association between alterations in motor and cognitive dimensions of schizophrenia-spectrum disorders: A systematic review.

Motor and cognitive alterations in schizophrenia-spectrum disorders (SSD) share common neural underpinnings, highlighting the necessity for a thorough exploration of the connections between these areas. This relationship is crucial, as it holds potential significance in unraveling the underlying mechanisms of SSD pathophysiology, ultimately leading to advancements in clinical staging and treatment strategies. The purpose of this review was to characterize the relationship between different hyper and hypokinetic domains of motor alterations and cognition in SSD. We systematically searched the literature (PROSPERO protocol CRD42019145964) and selected 66 original scientific contributions for review, published between 1987 and 2022. A narrative synthesis of the results was conducted. Hyper and hypokinetic motor alterations showed weak to moderate negative correlations with cognitive function across different SSD stages, including before antipsychotic treatment. The literature to date shows a diverse set of methodologies and composite cognitive scores hampering a strong conclusion about which specific cognitive domains were more linked to each group of motor alterations. However, executive functions seemed the domain more consistently associated with parkinsonism with the results regarding dyskinesia being less clear. Akathisia and catatonia were scarcely discussed in the reviewed literature. The present review reinforces the intimate relationship between specific motor alterations and cognition. Identified gaps in the literature challenge the formulation of definitive conclusions. Nevertheless, a discussion of putative underlying mechanisms is included, prompting guidance for future research endeavors.

The relationship between the gut microbiota and oxidative stress in the cognitive function of schizophrenia: A pilot study in China.

Cognitive impairment is a core symptom of schizophrenia. The gut microbiota (GM) and oxidative stress may play important roles in the pathophysiological mechanisms of cognitive impairment. This study aimed to explore the relationship between GM and oxidative stress in the cognitive function of schizophrenia. GM obtained by 16S RNA sequencing and serum superoxide dismutase (SOD) levels from schizophrenia patients (N = 68) and healthy controls (HCs, N = 72) were analyzed. All psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Correlation analysis was used to explore the relationship between GM, SOD, and cognitive function. Machine learning models were used to identify potential biomarkers. Compared to HCs, the relative abundances of Collinsella, undefined Ruminococcus, Lactobacillus, Eubacterium, Mogibacterium, Desulfovibrio, Bulleidia, Succinivibrio, Corynebacterium, and Atopobium were higher in patients with schizophrenia, but Faecalibacterium, Anaerostipes, Turicibacter, and Ruminococcus were lower. In patients with schizophrenia, the positive factor, general factor, and total score of MCCB positively correlated with Lactobacillus, Collinsella, and Lactobacillus, respectively; SOD negatively correlated with Eubacterium, Collinsella, Lactobacillus, Corynebacterium, Bulleidia, Mogibacterium, and Succinivibrio, but positively correlated with Faecalibacterium, Ruminococcus, and MCCB verbal learning index scores; Faecalibacterium and Turicibacter were positively correlated with MCCB visual learning index scores and speed of processing index scores, respectively. Our findings revealed a correlation between SOD and GM and confirmed that cognitive dysfunction in patients with schizophrenia involves abnormal SOD levels and GM changes.

Transient Fever Response After ECT in a Patient with Catatonic Schizophrenia: A Case Report. / Katatonik Sizofreni Hastasinda EKT Sonrasi Ortaya Çikan Geçici Ates Yaniti: Olgu Sunumu.

Electroconvulsive therapy (ECT) is an effective and safe treatment method for many psychiatric disorders. In general medical practice, ECT may cause side effects as most other treatment methods do. Headache, myalgia, nausea, vomiting, confusion, anterograde amnesia are common side effects of electroconvulsive therapy. Fever; in addition to general medical conditions such as infection, malignancy, connective tissue diseases, drug treatments, malignant hyperthermia, convulsions, it can also occur due to conditions such as neuroleptic malignant syndrome (NMS), serotonin syndrome, catatonia, malignant catatonia, which are frequently encountered in psychiatry clinics. In the literature, transient fever response due to electroconvulsive therapy application have been described, albeit rarely. Although there are many proposed mechanisms for the emergence of a fever response, regardless of its cause, it is still not understood why some fever responses occur. In this article, we present the differential diagnosis of the fever response, possible causes, and the mechanisms that may reveal the secondary fever response to electroconvulsive therapy in a case with a diagnosis of catatonic schizophrenia, who developed a fever response during electroconvulsive therapy sessions and no fever response was observed at times other than electroconvulsive therapy sessions. In this case, postictal benign fever response associated with electroconvulsive therapy was considered after excluding other medical conditions that may cause a fever response after electroconvulsive therapy. Keywords: ECT, Fever, Catatonia, NMS.

[Cerebral hemodynamic disorders in patients with schizophrenia with concomitant metabolic syndrome]. / Tserebral'nye gemodinamicheskie narusheniya u bol'nykh shizofreniei s metabolicheskim sindromom.

OBJECTIVE: To identify the differences or comparability of parameters of cerebral hemodynamics between patients with schizophrenia with or without concomitant metabolic syndrome (MS). MATERIAL AND METHODS: The study included 94 patients with schizophrenia (48 men and 46 women). A control group consisted of 40 mentally and somatically healthy individuals (17 men and 23 women) comparable in sex and age to the main group of patients. The diagnosis of metabolic syndrome was carried out according to the criteria of the International Diabetes Federation (IDF). Assessment of cerebral hemodynamics was carried out by 4 - channel rheoencephalography (REG) at rest with closed eyes. Data analysis was carried out using the Kraskel-Wallis ANOVA criterion with the procedure of automatic a posteriori pairwise comparison, the χ2 criterion and Spearman correlation analysis. RESULTS: According to the IDF criteria, 37 (39.4%) patients were diagnosed with MS. REG results revealed significantly (p<0.05) lower indicators of blood filling in the carotid basin, elasticity of the wall of the main arteries, the tone of small-caliber arteries and arterioles, as well as higher values of the tone of medium-caliber arteries in the carotid and vertebrobasilar basins, in both groups of patients with schizophrenia compared with the control group. In patients with schizophrenia with MS, compared with patients without MS, there were lower indicators of blood filling (p=0.044 and p=0.016) and elasticity of the wall of the main arteries (p=0.044 and p=0.028) in the carotid basin on the left and right sides. CONCLUSION: The presence of MS in patients with schizophrenia was accompanied by more pronounced disorders of cerebral blood flow in the form of a decrease in blood filling and elasticity of the wall of the main arteries in the carotid basin. The results indicate that patients with schizophrenia with MS should be considered as a group at increased risk of cerebrovascular diseases.

Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

The Effect of an Emotion Recognition and Expression Program on the Alexithymia, Emotion Expression Skills and Positive and Negative Symptoms of Patients with Schizophrenia in a Community Mental Health Center.

This study aimed to examine the effect of an emotion recognition and expression program (EREP) on the alexithymia, emotion expression skills and positive and negative symptoms of patients with schizophrenia. The study had a non-randomized, quasi-experimental design including a pretest, post-test, and follow-up test. It was conducted with 36 patients with schizophrenia (n = 18 intervention group, n = 18 control group) who regularly visited a Community Mental Health Center (CMHC) in Türkiye and participated voluntarily. The EREP was applied to the intervention group for eight weeks. "Personal Information Form", "Emotion Expression Scale (EES)", "Toronto Alexithymia Scale (TAS)", and "Positive Negative Syndrome Scale (PANSS)" were applied to all participants in the pretest, post-test, and follow-up test. The follow-up test was applied one month after the end of the sessions. Number, percentage, chi-square test, and repeated measures analysis of variance were used for data evaluation. In the total alexithymia score, there was a significant difference in the group interaction by time in the intervention group compared to the control group. In terms of total alexithymia score, the post-test and follow-up test mean scores of the intervention group were lower than the control group (p < 0.05; η2 = 0.122). There was a significant time*group interaction in the positive emotion subscale of the EES (p < 0.05; η2 = 0.121). The findings of our study indicated that the EREP had a positive effect on the alexithymia scores of patients with schizophrenia. We found that the EREP used in our study contributed to the reduction of alexithymia levels in patients with schizophrenia.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia.

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

Antipsychotic medications and sleep problems in patients with schizophrenia.

BACKGROUND: Sleep problems are common and related to a worse quality of life in patients with schizophrenia. Almost all patients with schizophrenia use antipsychotic medications, which usually increase sleep. Still, the differences in subjective sleep outcomes between different antipsychotic medications are not entirely clear. METHODS: This study assessed 5466 patients with schizophrenia and is part of the nationwide Finnish SUPER study. We examined how the five most common antipsychotic medications (clozapine, olanzapine, quetiapine, aripiprazole, and risperidone) associate with questionnaire-based sleep problems in logistic regression analyses, including head-to-head analyses between different antipsychotic medications. The sleep problems were difficulties initiating sleep, early morning awakenings, fatigue, poor sleep quality, short (≤6 h) and long sleep duration (≥10 h). RESULTS: The average number of antipsychotic medications was 1.59 per patient. Clozapine was associated with long sleep duration (49.0 % of clozapine users vs 30.2 % of other patients, OR = 2.05, 95 % CI 1.83-2.30, p < .001). Olanzapine and risperidone were in head-to-head analyses associated with less sleep problems than patients using aripiprazole, quetiapine, or no antipsychotic medication. Aripiprazole and quetiapine were associated with more insomnia symptoms and poorer sleep quality. Patients without antipsychotic medications (N = 159) had poorer sleep quality than patients with antipsychotic use, and short sleep duration was common (21.5 % of patients not using antipsychotics vs 7.8 % of patients using antipsychotics, OR = 2.97, 95 % CI 1.98-4.44, p < .001). CONCLUSIONS: Prevalence of sleep problems is markedly related to the antipsychotic medication the patient uses. These findings underline the importance of considering and assessing sleep problems when treating schizophrenia patients with antipsychotics.

Integrating Clinical Neuropsychology and Psychotic Spectrum Disorders: A Systematic Analysis of Cognitive Dynamics, Interventions, and Underlying Mechanisms.

Background and Objectives: The study aims to provide a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It focuses on the critical aspects of cognitive impairments, diagnostic tools, intervention efficacy, and the roles of genetic and environmental factors in these disorders. The paper emphasizes the diagnostic significance of neuropsychological tests in identifying cognitive deficiencies and their predictive value in the early management of psychosis. Materials and Methods: The study involved a systematic literature review following the PRISMA guidelines. The search was conducted in significant databases like Scopus, PsycINFO, PubMed, and Web of Science using keywords relevant to clinical neuropsychology and psychotic spectrum disorders. The inclusion criteria required articles to be in English, published between 2018 and 2023, and pertinent to clinical neuropsychology's application in these disorders. A total of 153 articles were identified, with 44 ultimately included for detailed analysis based on relevance and publication status after screening. Results: The review highlights several key findings, including the diagnostic and prognostic significance of mismatch negativity, neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups. The studies evaluated underline the role of neuropsychological tests in diagnosing psychiatric disorders and emphasize early detection and the effectiveness of intervention strategies based on cognitive and neurobiological markers. Conclusions: The systematic review underscores the importance of investigating the neuropsychological components of psychotic spectrum disorders. It identifies significant cognitive impairments in attention, memory, and executive function, correlating with structural and functional brain abnormalities. The paper stresses the need for precise diagnoses and personalized treatment modalities, highlighting the complex interplay between genetic, environmental, and psychosocial factors. It calls for a deeper understanding of these neuropsychological processes to enhance diagnostic accuracy and therapeutic outcomes.

Brain Abnormalities in Schizophrenia: A Comparative Imagistic Study.

Background and Objectives: Neuroimaging reveals a link between psychiatric conditions and brain structural-functional changes, prompting a paradigm shift in viewing schizophrenia as a neurodevelopmental disorder. This study aims to identify and compare structural brain changes found during the first schizophrenia episode with those found after more than 5 years of illness. Materials and Methods: This prospective study involved 149 participants enrolled between 1 January 2019 and 31 December 2021. The participants were categorized into three groups: the first comprises 51 individuals with an initial psychotic episode, the second consists of 49 patients diagnosed with schizophrenia for over 5 years, and a control group comprising 50 individuals without a diagnosis of schizophrenia or any other psychotic disorder. All participants underwent brain CT examinations. Results: The study examined all three groups: first-episode schizophrenia (FES), schizophrenia (SCZ), and the control group. The FES group had a mean age of 26.35 years and a mean duration of illness of 1.2 years. The SCZ group, with a mean age of 40.08 years, had been diagnosed with schizophrenia for an average of 15.12 years. The control group, with a mean age of 34.60 years, had no schizophrenia diagnosis. Structural measurements revealed widening of frontal horns and lateral ventricles in the SCZ group compared to FES and the FES group compared to the control group. Differences in the dimensions of the third ventricle were noted between SCZ and FES, while no distinction was observed between FES and the control group. The fourth ventricle had similar measurements in FES and SCZ groups, both exceeding those of the control group. Our results showed higher densities in the frontal lobe in schizophrenia patients compared to FES and the control group, with the control group consistently displaying the lowest densities. Conclusions: In summary, our comparative imaging analysis of schizophrenia patients, first-episode schizophrenia, and control patients revealed distinct ventricular patterns, with SCZ showing greater widening than FES and FES wider than the control group. Frontal lobe density, assessed via cerebral CT scans, indicated a higher density in the SCZ group in both anterior and posterior cortex portions compared to FES and the control group, while the left posterior cortex in FES had the highest density. These findings highlight unique neuroanatomical features across groups, shedding light on structural differences associated with different stages of schizophrenia.

Novel α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator LT-102: A promising therapeutic agent for treating cognitive impairment associated with schizophrenia.

AIMS: We aimed to evaluate the potential of a novel selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator, LT-102, in treating cognitive impairments associated with schizophrenia (CIAS) and elucidating its mechanism of action. METHODS: The activity of LT-102 was examined by Ca2+ influx assays and patch-clamp in rat primary hippocampal neurons. The structure of the complex was determined by X-ray crystallography. The selectivity of LT-102 was evaluated by hERG tail current recording and kinase-inhibition assays. The electrophysiological characterization of LT-102 was characterized by patch-clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests. RESULTS: LT-102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT-102 facilitated long-term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine-induced mouse model. Additionally, LT-102 treatment increased the protein level of brain-derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues. CONCLUSION: We conclude that LT-102 ameliorates cognitive impairments in a phencyclidine-induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS.

Efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination in post-schizophrenic depression: A randomized controlled trial.

Post-schizophrenic depression (PSD) increases the morbidity, mortality, and health burden in patients with schizophrenia. However, treatment of PSD is challenging due to the lack of substantial evidence of standard clinical practice. This study was aimed at comparing the efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination (OFC) in PSD. This was a randomized controlled trial conducted in sixty patients with PSD fulfilling the eligibility criteria. Recruited patients were randomized to receive either amisulpride at low dose (i.e., 100-300 mg/day) or OFC (5/10 mg + 20 mg) for eight weeks. The Calgary Depression Scale for Schizophrenia (CDSS), the Clinical Global Impression-Severity (CGI-S) and serum BDNF levels were assessed at baseline and after eight weeks of treatment. The change in the CDSS scores from baseline over eight weeks was significant in both the amisulpride and OFC groups. However, the changes were not significant when compared between the groups. Similarly, the changes in CGI-S scores and serum BDNF levels were significant in each group; but non-significant between the groups. A significant negative correlation was found between the changes in the CDSS scores and the serum BDNF levels in each group. No significant adverse events were noted in either group. Thus, to conclude, low-dose amisulpride can be a potential monotherapy in PSD with a favourable clinical outcome and safety profile (ClinicalTrials.gov ID: NCT04876521).

Self-assessment scale of auditory verbal hallucinations (SAVH): A novel tool for patients with schizophrenia.

BACKGROUND: A scale for self-assessment of auditory verbal hallucinations (SAVH) was developed for patients, and this study aimed to validate the scale by investigating its psychometric properties. METHODS: Forty one patients with schizophrenia or schizoaffective disorders (DSM-5) self-assessed their hallucinations using nine SAVH questions. Each question was scored from 0 to 5, indicating the severity of the symptoms. Patients were also evaluated with the Brief Psychiatric Rating Scale (BPRS), Auditory Hallucination Rating Scale (AHRS), and Birchwood Insight Scale (BIS). The psychometric properties of the SAVH were assessed by the face, internal consistency, construct, convergent and discriminant validities. RESULTS: SAVH scores were used to examine the psychometric properties. Cronbach's α and Guttman's Lambda-6 were 0.67 and 0.73 respectively. Significant correlations were observed between SAVH and AHRS total scores, as well as BPRS hallucinatory behavior subscores. No significant correlations were found between total SAVH scores and (i) levels of insight or (ii) negative BPRS subscores. Factor analysis on SAVH revealed three factors accounting for 59.3 % of the variance. Most patients found the questions clear, appropriate, and of adequate length. CONCLUSIONS: SAVH demonstrated good psychometric properties, suggesting its utility in assessing auditory verbal hallucinations (AVH). This self-assessment could be valuable in evaluating AVH treatment efficacy, monitoring AVH, and empowering patients.

Longitudinal study of insomnia, suicidal ideation, and psychopathology in schizophrenia.

OBJECTIVE: Insomnia is a common comorbidity in schizophrenia. Increasing cross-sectional evidence suggests an association between insomnia and suicidal ideation (SI) and symptom severity in schizophrenia. We investigated longitudinal associations over 3 months between insomnia, suicidal ideation, and symptom severity in a group of patients with chronic schizophrenia. METHOD: We performed a secondary analysis of data from n = 305 participants from the Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy (PROACTIVE) schizophrenia trial using regression models. RESULTS: The prevalence of moderate-to-severe insomnia was 17.7 % at baseline and 13.6 % at 3 months, respectively. The prevalence of SI was 22 % at baseline and 22.5 % at 3 months. After controlling for potential confounders, improved SI from baseline to 3 months was associated with both baseline moderate-to-severe insomnia (OR = 3.81, 95 % CI 1.11-13.12, p = 0.034) and improvement in insomnia (OR = 3.50, 95 % CI 1.23-9.92, p = 0.013). Worsening SI from baseline to 3 months was associated with worsening insomnia (OR = 3.50, 95 % CI 1.23-9.92, p = 0.013), but not baseline insomnia. Improvement in BPRS total score from baseline to 3 months was associated with improvement in insomnia (ß = 0.17, p = 0.029), but not baseline insomnia. CONCLUSION: Insomnia is common in patients with chronic schizophrenia and insomnia showed significant associations with SI and psychopathology. Clinicians should consider insomnia when assessing suicide risk in patients with schizophrenia.