Positive And Negative Syndrome Scale General Psychopathology Research Articles

NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ)risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder's clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation.

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China.

Prior studies have noted great variability in the plasma levels of risperidone (RIS). Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption, metabolism, and other predictors of metabolic dysregulation; however, these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain. To ascertain the characteristics of chronic schizophrenic patients treated with RIS, and to assess their relationship with plasma RIS levels. This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service. The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography. The patients' demographic and clinical characteristics, and psychopathologies were assessed, and the associations between clinical variables and plasma levels of RIS were explored. Male patients received higher doses of RIS than female ones, but plasma concentrations of RIS and risperidone + 9-hydroxyrisperidone (active moiety) were higher in female patients. Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS) were significantly positively correlated with plasma concentrations of risperidone + 9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects. In male subjects, we found a statistically significant positive correlation between the concentrations of risperidone + 9-hydroxyrisperidone in plasma/(dose × kg) and age, mean PANSS negative subscale scores, mean PANSS general psychopathology subscale scores, and mean PANSS total scores. Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

BackgroundInflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology.MethodsThe study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function.ResultsSerum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P < 0.05). MMP-2 levels were positively correlated with TNF-α levels (P < 0.05), but not with cognitive function (P > 0.05).ConclusionThe results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia.

Previous electroencephalography (EEG) studies have indicated altered brain oscillatory α-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized α-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual α-peak-frequency-guided rTMS (αTMS) on treatment-refractory schizophrenia. We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this doubleblind, sham-controlled study. We randomized patients to a 3-week course of either active αTMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. We included 44 patients. After treatment, we observed a significantly higher PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the αTMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received αTMS compared with sham stimulation (p = 0.048). The limited number of study participants included only male patients. Depression was not formally evaluated. Navigated αTMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual α-peak-frequency-guided rTMS in treatment-refractory schizophrenia. NCT01941251; ClinicalTrials.gov.

Systematic Review and Meta-analysis of Exercise Interventions for Psychotic Disorders: The Impact of Exercise Intensity, Mindfulness Components, and Other Moderators on Symptoms, Functioning, and Cardiometabolic Health.

Exercise therapy has been shown to be an effective complementary treatment for patients with psychotic disorders. However, the specific impacts of different training modalities remain poorly understood. This article aims to quantitatively review the moderating influence of different exercise modalities, hypothesizing that higher exercise intensity as well as utilization of mindfulness-based exercise (MBE) components, will improve intervention outcomes. PubMed, Web of Science, and PsycINFO were searched from 2010 to March 2022 for randomized controlled trials investigating exercise interventions in patients with psychotic disorders (preregistration: https://doi.org/10.17605/OSF.IO/J8QNS). Outcomes considered were positive/negative symptoms, Positive and Negative Syndrome Scale (PANSS) General Psychopathology/Total scores, depressive symptoms, psychosocial functioning, quality of life, cardiorespiratory fitness, and body mass index. Separate meta-analyses, including moderator analyses, were performed to evaluate the moderating influence of different training modalities. Of 6653 studies, 40 (n = 2111 patients) were included in the meta-analysis. The effects of moderate-intensity exercise exceed low-intensity approaches for PANSS Total scores (P = .02) and depressive symptoms (P = .04). The presence of MBE components was associated with improvements in positive symptoms (P = .04) and PANSS General Psychopathology subscores (P = .04) but also with higher error and between-study heterogeneity. Our analysis also shows improved intervention effects on depression in younger patients (P = .012) and improved psychosocial functioning scores following more frequent sessions (P < .01). A minimum of moderate intensity should be considered. More frequent training sessions per week also seem to be beneficial. While adding mindfulness elements is promising, it increases heterogeneity and requires caution in terms of generalization.

Correlation analysis and gender differences of cognitive function based on mini-mental state examination (MMSE) and suicidal tendency in patients with schizophrenia

BackgroundThe aim of this study was to investigate the correlation and gender differences between cognition and suicidal tendency in patients with schizophrenia.MethodsA total of 554 patients with schizophrenia were recruited. The Mini-Mental State Examination (MMSE), Positive and Negative Syndrome Scale (PANSS), Interpersonal Reactivity Index (IRI), Toronto Alexithymia Scale (TAS), and Insomnia Severity Index (ISI) were used to assess clinical symptoms.ResultsIn male patients, MMSE score and the incidence of suicidal tendency were correlated (P = 0.04, OR = 1.06, 95%CI: 1.00–1.12). Among patients with cognitive dysfunction, IRI score (P = 0.01, OR = 1.04, 95%CI: 1.01–1.06), and types of antipsychotic drugs (P < 0.01, OR = 3.97, 95%CI: 1.76–8.97) in male patients were associated risk factors for suicidal ideation. Among patients without cognitive dysfunction, PANSS positive subscale score (P = 0.03, OR = 1.06, 95%CI: 1.01–1.11), and PANSS general psychopathology score (P = 0.02, OR = 1.05, 95%CI: 1.01–1.08) were associated risk factors for suicidal ideation in male patients and PANSS positive subscale score (P < 0.01, OR = 1.15, 95%CI: 1.05–1.26) were associated risk factors for suicidal ideation in female patients.ConclusionsThere were significant gender differences in the correlation between cognitive functioning and suicidal ideation in patients with schizophrenia. Cognitive function may play an important mediating role in other factors on suicide.

The Relationship Between Depressive Symptoms and Psychological Variables in Patients With Schizophrenia.

Depressive symptoms are common in schizophrenia and can be seen at any stage of the disease. Although various models have been proposed to explain the development of depression in schizophrenia, studies investigating related psychological factors are scarce and the studies that have been done usually focus on only a small number of possible factors. The goal of this study was to investigate the predictability of some psychological factors on depression in patients with schizophrenia. For this purpose, patients with high and low depression scores were compared. Two groups of individuals with schizophrenia, with (n=29) and without (n=31) depression, as determined by scores on the Calgary Depression Scale in Schizophrenia, were compared using a sociodemographic data form, the Positive and Negative Syndrome Scale (PANSS), the Beck Anxiety Inventory, the Rotter Internal-External Locus 2024 of Control Scale, the Multidimensional Scale of Perceived Social Support, and the Stress Coping Styles Scale. No differences were found between the 2 groups in terms of sociodemographic and clinical characteristics, social support scores, and coping styles. Statistically significant differences were found between the groups on the PANSS positive, negative, and general psychopathology subscales, in PANSS total scores, in anxiety scores, and in locus of control scores. This study showed that high levels of negative, positive, and general psychopathological symptoms, external locus of control, and high anxiety scores may be predictive of depression in individuals with schizophrenia. Studies that examine psychological factors in larger patient groups may provide the opportunity to detect and target these factors earlier in the course of schizophrenia, thereby reducing morbidity and mortality.

Relationship between blood-based inflammatory indices and clinical score of schizophrenia patients: A cross-sectional study

Schizophrenia is a severe mental disorder that may involve inflammation. Inflammatory indices, such as the neutrophil to lymphocyte ratio (NLR), the monocyte to lymphocyte ratio (MLR), the platelet to lymphocyte ratio (PLR), and the systemic inflammation index (SII), are simple and inexpensive measures of inflammation that have been associated with various diseases. However, few studies have compared these indices and their relationships with clinical symptoms in schizophrenia. We conducted a cross-sectional study of 121 schizophrenia patients (101 males, 20 females). We measured the blood-based inflammatory indices (NLR, MLR, PLR, and SII) and assessed the clinical symptoms of schizophrenia using the Positive and Negative Syndrome Scale (PANSS). Statistical analyses were performed to examine the correlations and effects of the inflammatory indices on PANSS scores. We found that NLR, MLR, PLR, and SII were positively correlated with PANSS total score, PANSS positive score, PANSS negative score, and general psychopathology score (adjusted P < 0.02 for all correlations). Subgroup analysis showed that correlations between inflammatory indices and the clinical scores differed by gender. In males, all inflammatory indices were positively correlated with all clinical scores. On the other hand, in females, only NLR and SII were positively correlated with all clinical scores. After adjusting for confounders, we also found that NLR was a predictor of PANSS total score (β = 23, adjusted P < 0.02), PANSS positive score (β = 2.6, adjusted P = 0.03), PANSS negative score (β = 6.8, adjusted P < 0.02), and PANSS general psychopathology score (β = 13.6, adjusted P < 0.02), while SII was only a predictor for PANSS total score (β = −0.00003, adjusted P = 0.01) and general psychopathology scores (β = −0.00002, adjusted P < 0.02). These findings suggest that inflammation is involved in the pathophysiology and clinical manifestations of schizophrenia, and that blood-based inflammatory indices may serve as screening tools or indicators for the inflammatory status and severity of symptoms of schizophrenia patients.

Association between suicidal behavior and impaired glucose metabolism in first-episode drug-naïve patients with schizophrenia

BackgroundSchizophrenia (SZ) patients have been reported to have comorbid suicidal behavior (SB) and impaired glucose metabolism in early psychosis, but it is unclear whether impaired glucose metabolism plays a role in the occurrence of SB in patients with first-episode drug-naïve (FEDN) SZ. Therefore, our main aim was to examine the relationship between SB and glucose metabolism in FEDN SZ patients. MethodsWe recruited 319 FEDN SZ patients and collected information on their sociodemographic characteristics, clinical data, and glucose metabolism parameters. Participants' psychotic and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAMD), respectively. Fasting plasma glucose and insulin levels were also measured. ResultsThe percentage of FEDN SZ patients with SB was 45.5% (145/319). Compared to SZ patients without SB, SZ patients with SB exhibited higher scores on HAMD, PANSS positive subscale, as well as higher levels of fasting plasma glucose, fasting plasma insulin, and homeostasis model assessment of insulin resistance index (all p<0.05). Logistic regression analysis indicated that increased levels of insulin resistance (adjusted OR = 1.920), body mass index (adjusted OR = 0.931), and PANSS general psychopathology (adjusted OR = 1.041) were independently associated with SB. The Receiver Operating Characteristic Curve showed an Area Under Curve value of 0.732 for the combination of three factors in regression model to distinguish between SB and non-SB. ConclusionsOur results indicate that fasting glucose, fasting insulin, and insulin resistance are strongly associated with SB in FEDN SZ patients, suggesting that glucose metabolism abnormalities may be potential biomarkers of SB in SZ patients. Regular monitoring of glucose metabolism variables is essential for suicide prevention.

Correlation of motor-auditory cross-modal and auditory unimodal N1 and mismatch responses of schizophrenic patients and normal subjects: an MEG study.

It has been suggested that the positive symptoms of schizophrenic patients (hallucinations, delusions, and passivity experience) are caused by dysfunction of their internal and external sensory prediction errors. This is often discussed as related to dysfunction of the forward model that executes self-monitoring. Several reports have suggested that dysfunction of the forward model in schizophrenia causes misattributions of self-generated thoughts and actions to external sources. There is some evidence that the forward model can be measured using the electroencephalography (EEG) and magnetoencephalography (MEG) components such as N1 (m) and mismatch negativity (MMN) (m). The objective in this MEG study is to investigate differences in the N1m and MMNm-like activity generated in motor-auditory cross-modal tasks in normal control (NC) subjects and schizophrenic (SC) patients, and compared that activity with N1m and MMNm in the auditory unimodal task. The N1m and MMNm/MMNm-like activity were recorded in 15 SC patients and 12 matched NC subjects. The N1m-attenuation effects and peak amplitude of MMNm/MMNm-like activity of the NC and SC groups were compared. Additionally, correlations between MEG measures (N1m suppression rate, MMNm, and MMNm-like activity) and clinical variables (Positive and Negative Syndrome Scale (PANSS) scores and antipsychotic drug (APD) dosages) in SC patients were investigated. It was found that (i) there was no significant difference in N1m-attenuation for the NC and SC groups, and that (ii) MMNm in the unimodal task in the SC group was significantly smaller than that in the NC group. Further, the MMNm-like activity in the cross-modal task was smaller than that of the MMNm in the unimodal task in the NC group, but there was no significant difference in the SC group. The PANSS positive symptoms and general psychopathology score were moderately negatively correlated with the amplitudes of the MMNm-like activity, and the APD dosage was moderately negatively correlated with the N1m suppression rate. However, none of these correlations reached statistical significance. The findings suggest that schizophrenic patients perform altered predictive processes differently from healthy subjects in latencies reflecting MMNm, depending on whether they are under forward model generation or not. This may support the hypothesis that schizophrenic patients tend to misattribute their inner experience to external agents, thus leading to the characteristic schizophrenia symptoms.

Clinical and metabolic associations of obesity and body mass index in antipsychotic-naïve first-episode schizophrenia patients and nonadherent chronic patients

Aim of the studyWe investigated the association between obesity and body mass index (BMI) with Positive and Negative Syndrome Scale (PANSS) psychopathology, age at disease onset, and parameters linked to the metabolic syndrome (fasting plasma lipid and glucose levels), among antipsychotic-naïve first-episode schizophrenia (AN-FES) patients and nonadherent chronic schizophrenia individuals.Subject or material and methodsWe recruited a total of 187 AN-FES patients or nonadherent chronic individuals for this study. Clinical and anthropometric data together with plasma lipid and glucose parameters were collected immediately after patients’ admission to the hospital. Patients were classified as obese with body mass index (BMI) ≥ 30, or as non-obese if overweight (BMI: 25 – 29.9) or of normal body weight (BMI: 18.5 – 24.9).ResultsAfter controlling for the possible confounders we found that only BMI significantly predicted clinical and metabolic variables. Among AN-FES patients, higher BMI values predicted lower levels of HDL cholesterol (HDL-c), and higher ratios for LDL cholesterol (LDL-c)/HDL-c and triglyceride/HDL-c, while among nonadherent individuals, higher BMI values predicted higher number of psychotic episodes, and lower PANSS general psychopathology scores. The contribution of BMI ranged from approximately 5.8% to 29.6%, with the lowest contribution observed for number of psychotic episodes, and the highest contribution for the LDL-c/HDL-c ratio.DiscussionOur results indicate that AN-FES patients and nonadherent chronic patients differed in the effects of BMI.ConclusionsHigher BMI contributes to an increased risk for dyslipidemia among AN-FES patients and to the higher number of psychotic episodes, and less severe clinical psychopathology among nonadherent chronic schizophrenia individuals.

Efficacy and acceptability of adjunctive n-acetylcysteine for psychotic disorders: Systematic review and meta-analysis.

N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to evaluate the efficacy and acceptability of NAC as an augmentation strategy for psychotic disorders. PubMed, Web of Science, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched until the date of November 28, 2022. The inclusion criteria were randomized controlled trials (RCTs) comparing NAC and placebo in patients with psychotic disorders. The outcomes were the psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and drop-out rates. A total of 594 patients from eight trials were included. The results showed that no difference was found in score changes of PANSS total, positive, negative, or general psychopathology scale scores between the NAC group and placebo group in both time points (≤24weeks and >24weeks). There was also no statistical difference in drop-out rates between the two groups. For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.

A pilot study to investigate the efficacy and tolerability of lesion network guided transcranial electrical stimulation in outpatients with psychosis spectrum illness

BackgroundTranscranial electrical stimulation (tES) may improve psychosis symptoms, but few investigations have targeted brain regions causally linked to psychosis symptoms. We implemented a novel montage targeting the extrastriate visual cortex (eVC) previously identified by lesion network mapping in the manifestation of visual hallucinations. ObjectiveTo determine if lesion network guided High Definition-tES (HD-tES) to the eVC is safe and efficacious in reducing symptoms related to psychosis. MethodsWe conducted a single-blind crossover pilot study (NCT04870710) in patients with psychosis spectrum disorders. Participants first received HD-tDCS (direct current), followed by 4 weeks of wash out, then 2 Hz HD-tACS (alternating current). Participants received 5 days of daily (2×20 min) stimulation bilaterally to the eVC. Primary outcomes included the Positive and Negative Syndrome Scale (PANSS), biological motion task, and Event Related Potentials (ERP) from a steady state visual evoked potential (SSVEP) paradigm. Secondary outcomes included the Montgomery-Asperg Depression Rating Scale, Global Assessment of Functioning (GAF), velocity discrimination and visual working memory task, and emotional ERP. ResultsHD-tDCS improved PANSS general psychopathology in the short-term (d=0.47; pfdr=0.03), with long-term improvements in general psychopathology (d=0.62; pfdr=0.05) and GAF (d=−0.56; pfdr=0.04) with HD-tACS. HD-tDCS reduced SSVEP P1 (d=0.25; pfdr=0.005), which correlated with general psychopathology (β = 0.274, t = 3.59, p = 0.04). No significant differences in safety or tolerability measures were identified. ConclusionLesion network guided HD-tES to the eVC is a safe, efficacious, and promising approach for reducing general psychopathology via changes in neuroplasticity. These results highlight the need for larger clinical trials implementing novel targeting methodologies for the treatments of psychosis.

Interaction between high interleukin-2 and high cortisol levels is associated with psychopathology in patients with chronic schizophrenia

BackgroundBoth cortisol and interleukins appear at abnormal levels in schizophrenia. Our previous study has shown that cortisol and interleukins are associated with psychopathology and response to antipsychotic medications in a relatively small sample size of patients with schizophrenia. The current study was designed to investigate how cortisol, interleukins (ILs) and their interactions would correlate with clinical presentation in a relatively large sample size of patients with schizophrenia. MethodsWe compared serum cortisol, IL-2, IL-6, and IL-8 levels in 162 medicated schizophrenia patients (including 27 patients in remission) and 62 healthy controls. Serum levels of cortisol and interleukins were measured by radioimmunoassay and quantitative ELISA, respectively. Clinical symptoms were assessed according to the Positive and Negative Syndrome Scale (PANSS). ResultsPatients with schizophrenia had significantly higher levels of cortisol and IL-2 compared to controls. Patients in remission had higher levels of IL-6 than non-remitting patients. PANSS positive symptoms, general psychopathology, cortisol and IL-2 were the most central nodes in the cortisol-IL-symptom network. The interaction between cortisol and IL-2 was associated with PANSS positive symptoms, general psychopathology and depressive factor. For patients with cortisol level above the median, IL-2 was negatively associated with PANSS positive symptoms and general psychopathology. ConclusionsOur results indicated that the interaction between cytokines and cortisol may be associated with the pathophysiology of some symptoms in chronic schizophrenia. In particular, the interaction between cortisol and IL-2 is associated with the clinical phenotypes of schizophrenia.

Body mass index, waist circumference, insulin, and leptin plasma levels differentiate between clozapine-responsive and clozapine-resistant schizophrenia.

Between 25% and 50% of patients suffering from treatment-resistant schizophrenia fail to achieve a clinical response with clozapine. The rapid identification and treatment of this subgroup of patients represents a challenge for healthcare practice. To evaluate the relationship between metabolic alterations and the clinical response to clozapine. A multicenter, observational, case-control study was performed. Patients diagnosed with schizophrenia treated with clozapine were eligible (minimum dose 400 mg/d for at least 8 weeks and/or clozapine plasma levels ⩾ 350 µg/mL). According to the Positive and Negative Syndrome Scale (PANSS) total score, patients were classified as clozapine-responsive (CR) (<80 points) or clozapine non-responsive (CNR) (⩾80 points). Groups were compared based on demographic and treatment-related characteristics, together with body mass index (BMI), waist circumference, insulin, leptin, and C-reactive protein plasma levels. Plasma levels of clozapine and its main metabolite, nor-clozapine, were measured in all the participants. In addition, the potential relationship between PANSS scores and leptin or insulin plasma levels was assessed. A total of 46 patients were included: 25 CR and 21 CNR. BMI and waist circumference, fasting insulin and leptin plasma levels were lower in the CNR group, while C-reactive protein was not different. Moreover, significant negative correlations were observed between PANSS positive and general psychopathology subscores, on one hand, and insulin and leptin plasma levels, on the other hand, as well as between PANSS negative subscores and leptin plasma levels. Our results suggest that the lack of metabolic effect induced by clozapine is associated with the lack of clinical response.

Sex differences in the association between suicidal ideation and neurocognitive function in Chinese patients with schizophrenia.

There is increasing evidence that sex differences exist in many clinical manifestations of patients with schizophrenia, including suicidal ideation (SI) and neurocognitive function. The present study was performed to explore the sex differences in the association between SI and neurocognitive function in Chinese patients with schizophrenia. A total of 1188 inpatients with schizophrenia were recruited from multicenter psychiatric hospitals. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to evaluate the neurocognitive function of all patients. The Positive and Negative Syndrome Scale (PANSS) was utilized to assess the psychopathology of patients. The Beck Scale for Suicide Ideation (BSSI) was used to assess the severity of SI. In male patients, the suicide risk score was significantly associated with PANSS negative symptoms (r = 0.167, p = 0.043), visuospatial subscale (r = -0.261, p = 0.001), and RBANS total scores (r = -0.172, p = 0.037). Furthermore, multivariate linear regression analysis showed that the visuospatial subscale (β = -0.490, t = -3.273, p = 0.001) was independently associated with the suicide risk score in male patients. In female patients, the suicide risk score was significantly correlated with PANSS positive symptoms (r = 0.249, p = 0.021), negative symptoms (r = 0.394, p < 0.001), general psychopathology (r = 0.276, p = 0.01) and PANSS total score (r = 0.365, p = 0.001). Multivariate linear regression analysis showed that PANSS negative symptoms (β = 1.849, t = 3.933, p = 0.001) were significantly associated with suicide risk scores in female patients. Our findings indicate that there are sex differences in the association between SI and neurocognitive function in patients with schizophrenia. Based on the findings of our study, gender-specific prevention and intervention strategies may make a difference in reducing SI in Chinese schizophrenia patients.

Suicidal ideation in Chinese adults with schizophrenia: associations with neurocognitive function and empathy

BackgroundSuicidal ideation is common among people diagnosed with schizophrenia spectrum disorders and may be related to neurocognitive, social cognitive, and clinical variables. This study aimed to investigate the relationships between suicidal ideation and both neurocognitive function and empathy.MethodsThe sample for this cross-sectional study comprised 301 schizophrenic patients aged 18–44 years. All participants were administered the Beck Scale for Suicide Ideation—Chinese Version (BSI—CV), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Interpersonal Reactivity Index (IRI), and the Positive and Negative Syndrome Scale (PANSS). The demographic and clinical data of the patients were also collected.ResultsIn total, 82 patients reported suicidal ideation. Compared to patients without suicidal ideation, patients with suicidal ideation showed significant differences in the IRI-Personal Distress subscale, PANSS-General Psychopathology symptom scores, and suicide attempts. Moreover, there were moderating effects of neurocognitive function and empathy on the relationship between suicide attempts and suicidal ideation.ConclusionsThese results indicate that the personal distress component of empathy, general psychopathology symptoms and suicide attempts are independent risk factors for suicidal ideation in Chinese adults with schizophrenia. Moreover, neurocognitive function may also be related to suicidal ideation through a moderating relationship. In order to reduce suicidal ideation among patients with schizophrenia, early screening of empathy and neurocognitive function is essential.

Positive and Negative Syndrome Scale (PANSS) predictors of hospitalization during home treatment on 1045 patients with schizophrenia in acute crisis

IntroductionSeveral factors related to the risk of requiring psychiatric hospitalization have been described in patients diagnosed with schizophrenia treated with methods other than home treatment. With regard to the symptoms, high global illness severity and positive symptoms of schizophrenia have been most frequently related to the risk of hospitalization in patients with schizophrenia. However, there are no studies describing which clinical factors increase the likelihood of being hospitalized while undergoing home follow-up.ObjectivesTo determine which of the clinical factors assessed in the PANSS predict the risk of hospitalization in patients diagnosed with schizophrenia following a home treatment program.MethodsAll patients with schizophrenia who were visited by a home treatment team in Barcelona between January 2017 and December 2021 were included in the study. A comparative, bivariate analysis of each item of the PANSS and of the global results of each category was conducted on those who were hospitalized and those who were not hospitalized. Finally, a logistic regression of each category of the PANSS was done on both groups, controlling for other socio-demographic and clinical factors.ResultsA total of 1045 patients with schizophrenia were evaluated in this study. PANSS positive symptom subscale (PANSS-S), PANSS General Psychopathology, PANSS Excited Component and PANSS Global Score scored higher in patients who were finally hospitalized in a conventional acute treatment unit. Regarding the PANSS negative symptom subscale, no significant differences were found between the two groups.In patients who required hospitalization, the scores of all the PANSS positive symptom subscale (PANSS-P) items and all items on the PANSS excited component (excitement, tension, hostility, uncooperativeness and poor impulse control) were significantly higher. Some items regarding general psychopathology (Somatic concern, anxiety, guilt feelings, tension, and mannerisms) were also significantly higher in the hospitalization group. Only 3 items—blunted affect, guilt feelings and motor retardation—scored significantly higher in patients who did not require hospitalization. In the logistic regression, only the global score of the PANSS-P reached statistical significance (P = 0.001).ConclusionsPositive symptoms scored in the PANSS seem to be the most predictive factors of hospitalization regarding clinical symptoms in patients with Schizophrenia following home treatment. Other items regarding exciting symptoms and general psychopathology also showed as relevant regarding the risk of conventional hospitalization in those patients.Disclosure of InterestNone Declared

Brexpiprazole augmentation in a clozapine-resistant young schizophrenic patient: a successful case report.

IntroductionAlthough clozapine is considered the most effective drug for Treatment Resistant Schizophrenia (TRS), only 40% of patients treated will meet clinical response. Literature reviews and meta-analytic data offer no definite conclusions about the most effective clozapine augmentation strategies. Nevertheless, it has been suggested that the lack of evidence should not discourage clinicians from trying out new strategies in individual patients. Brexpiprazole is a novel 5-HT and DA modulator antipsychotic that exhibits partial agonism to D2/D3 and 5HT1A receptors, antagonism to 5HT2A and α-1B/2C receptors and represents a promising new drug in the pharmacotherapy of schizophrenia for both acute and maintenance treatment. In current literature there is no evidence of experiences in brexpiprazole augmentation for clozapine resistant patients.ObjectivesThis case report describes a successful clinical experience of brexpiprazole augmentation in a complicated case of clozapine resistant paranoid schizophrenia with consistent negative symptoms, the clinical evolution and metabolic improvement consequent to this therapy combination.MethodsIn a 27 male TRS patient, sequentially treated with adequate doses of risperidone, cariprazine, aripiprazole and olanzapine monotherapy, prescribed for adequate time, clozapine treatment was started, with a gradual titration from 25 to 300 mg/day, without significant clinical response on both positive and negative symptoms. Successively was introduced fluoxetine, from 10 to 30 mg/day, with no relevant clinical improvement. After 2 months of pharmacological stabilization with clozapine and fluoxetine described dosages, brexpiprazole was introduced starting from 1 mg/day and rapidly increasing till 4 mg/day.ResultsAfter 6 weeks of treatment, PANSS positive and negative subscales showed a significant decrease, respectively from 28 to 17 and from 42 to 20, while general psychopathology subscale decreased from 66 to 34. Negative sub-items with major improvement were those regarding blunted affect, emotional withdrawal, poor rapport, and passive/apathetic social withdrawal. Brexpiprazole augmentation also allowed to slowly decrease (in 6 months) clozapine dose till actual 150 mg/day, with a significant improvement in general tolerability and a slow decline in metabolic parameters (BMI from 36.5 to 30.3; fasting glucose from 112 to 92 mg/dL; total cholesterol from 248 to 182 mg/dL; total triglycerides from 392 to 198 mg/dL).ConclusionsIn this case report brexpiprazole augmentation in a clozapine resistant young schizophrenic patient was an effective strategy with significant symptoms improvement, in particular in PANSS general psychopathology and PANSS negative subscales. The consequent clozapine dose reduction contribute to the slow decrease in metabolic parameters considered.Disclosure of InterestNone Declared

Decreased plasma concentrations of kynurenine and kynurenic acid in schizophrenia patients

IntroductionThe kynurenine pathway of tryptophan catabolism has come into the spotlight of schizophrenia research since its catabolites exert neuroactive effects. A strong body of evidence suggests that kynurenic acid, a catabolite of kynurenine pathway, acts as the only endogenous NMDA receptor antagonist leading to the weakening of circuits in layer III of dorsolateral prefrontal cortex of schizophrenia patients. Studies exploring the levels of kynurenic acid and other metabolites of tryptophan in peripheral blood did not yield any definite conclusions.ObjectivesPrimary objective of this study was to assess differences in concentrations of key constituents of kynurenic pathway in blood plasma – tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) between schizophrenia patients (SCZ) and healthy controls (HC). Secondary objective was to explore correlations between these concentrations and clinical characteristics.MethodsIn our two-centre prospective case-control study we measured plasma concentrations of TRP, KYN and KYNA in 36 healthy controls (HC) and 38 schizophrenia (SCZ) patients during acute exacerbation and remission and explored the correlations with clinical parameters using PANSS scale. The patients were matched with HC by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.ResultsTRP concentrations were significantly higher in HC than in SCZ patients in acute phase (p&lt;0,001) and remission (p&lt;0,001), while SCZ patients in acute phase had significantly higher TRP levels than in remission (p&lt;0,01). Levels of KYNA and KYN were significantly lower in SCZ patients than in HC both in acute phase and remission, all with high statistical significance (p&lt;0,001). There was no statistically significant difference between acute phase and remission neither for KYN (p&gt;0,05), nor for KYNA (p&gt;0,05). There was no correlation of plasma levels of TRP, KYN and KYNA with total PANSS score, PANSS positive scale score, PANSS negative scale score and PANSS general psychopathology scores, both in acute phase and remission (p&gt;0,05). Also, there was no correlation between plasma levels of TRP, KYN and KYNA in SCZ patients in remission with improvements measured with PANSS scale (p&gt;0,05).ConclusionsAlthough there are concerns about the value of measurement of metabolites of kynurenine pathway in the peripheral blood, our data suggest that significantly decreased levels of KYN and KYNA could suggest that disrupted TRP degradation in SCZ patients may be reflected in the peripheral blood as well. Further studies of peripheral levels of kynurenine pathway metabolites on larger samples should also explore effects of antipsychotic therapy, but also their correlation with other clinical parameters such as neurocognition.Disclosure of InterestNone Declared