Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM.

Dopamine D2 receptor occupancy (D2RO) significantly influences the clinical effectiveness and safety of many antipsychotic drugs. Maintaining a D2RO range of 65%-80% provides the best antipsychotic effects while minimizing adverse reactions. Data from a Phase III trial were used to establish an exposure-response relationship for monthly intramuscular Risperidone ISM (75 and 100 mg) or placebo administered to adults with schizophrenia. Pharmacodynamic analysis was based on an Emax model for Positive and Negative Syndrome Scale (PANSS) developed in NONMEM. Plasma concentrations of the active moiety were derived using a previously developed population pharmacokinetic model, which was used for D2RO simulations in conjunction with a published Emax model. The optimal D2RO range (65%-80%) was reached for the median within hours following the first injection of both Risperidone ISM doses. At steady state, median D2RO for both doses remained above 65% throughout the 28-day dosing period and demonstrated lower variability than oral risperidone. PANSS response did not differ significantly between dose groups, most likely because active moiety concentrations had already reached the plateau of the concentration-response relationship. The pharmacokinetic/pharmacodynamic analysis showed a profound placebo effect (-11.7%), and an additional maximal drug effect (-6.6%) resulting in a total PANSS improvement over time of -18.3%. Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations.

Elevated serum IL-17 A and CCL20 levels as potential biomarkers in major psychotic disorders: a case-control study.

BACKGROUND: Major psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics. METHOD: We conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS). RESULTS: The mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1-15.3) pg/mL and 4.2 (3-5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20. CONCLUSION: The current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia.

Extension and Further Replication of the Reliability, Criterion Validity, and Treatment Sensitivity of the PANSS10 and PANSS20 for Pediatric Trials.

Introduction: The Positive and Negative Syndrome Scale (PANSS) is a widely accepted outcome measure for pediatric schizophrenia trials; however, it has notable limitations. Psychometric investigations have shown a multifactorial structure and some items have limited utility assessing symptom severity in children. To address these issues, we developed and evaluated optimized 10- and 20-item PANSS short-forms (PANSS10 and PANSS20) using patient-level clinical trial data. This study further assesses these optimized forms using independent clinical trial data. Methods: We examined patient-level data from a randomized pediatric schizophrenia trial comparing paliperidone ER to aripiprazole. Data were accessed through the Yale Open Data Access (YODA) secure platform. Analyses included confirmatory factor analyses, graded response models, ω score reliability, internal consistency, sensitivity to change, and criterion validity versus the Clinical Global Impressions of Severity (CGI-S). Bland-Altman analyses examined score calibration versus the 30-item PANSS and inclusion cut scores. Results: Participants (N = 288) were ages 12 to 17 years (M = 15.3, SD = 1.46; 66% male). Total scores for the PANSS10 and PANSS20 showed strong correlations with the 30-item PANSS (0.90 and 0.97, respectively). Average inter-item correlations were 0.10 and 0.14 and ωTotal reliabilities were 0.74 and 0.85. Both PANSS10 and PANSS20 scores showed reliability >0.80-2.3 to 4.5 SD and -3.0 to 6.0 SD about mean symptom severity, respectively. Sensitivity to treatment was also similar (partial eta squared 0.23 and 0.22), as was correlation with CGI-S at baseline (0.45 and 0.48; not significantly different). The mean item-average discrepancy with the 30-item PANSS was 0.095 for PANSS10 and 0.033 for PANSS20. Conclusions: The optimized PANSS forms continue to show impressive reliability, validity, and calibration compared with the 30-item PANSS. Researchers should consider replacing the 30-item PANSS with the PANSS10 as a clinical outcome and screening measure due to its length and psychometric performance.

Assessing the Trajectory of Schizophrenia Effectively in Order to Treat Effectively.

INTRODUCTION: Schizophrenia is a complex psychiatric disorder characterized by heterogeneous symptom trajectories that significantly impact patient outcomes. We believe that the study of the trajectories of Schizophrenia is useful in assessing treatment options and outcomes. While the Positive and Negative Syndrome scale is usually used on one occasion to measure symptoms at a single time, if measured repeatedly , the PANSS is also useful in measuring trajectories. In order to illustrate and promote this serial use, we have reviewed papers which describe the delineation of Trajectories of Symptoms in Schizophrenia based on PANSS scores. This review integrates findings from longitudinal studies focusing on the trajectories of positive symptoms, negative symptoms, the relation between positive and negative symptoms and cognition, soft neurological signs, and treatment response in schizophrenia. METHODS: Studies were identified from the PUBMED database .Studies included in this review employed diverse methodologies such as trajectory analyses, longitudinal assessments, and clinical trials. Data were extracted from a range of patient cohorts, including those with first-episode psychosis and chronic schizophrenia. RESULTS: Longitudinal studies consistently demonstrate variability in the trajectories of positive symptoms, with most patients experiencing early stable remission, though a subgroup exhibits persistent or fluctuating symptomatology. Negative symptoms, on the other hand, often show poor improvement over time, correlating with impaired social and neurocognitive functioning. Cognitive deficits also vary, with some domains showing improvement while others, such as logical memory, deteriorate in certain patient subgroups. The relationship between positive and negative symptom trajectories highlights their complex relationship, influencing overall functioning and treatment outcomes. Antipsychotic medications demonstrate varied responses across patient cohorts, with distinct trajectory patterns observed based on medication type and patient-specific factors such as co-morbid substance abuse and duration of untreated psychosis. CONCLUSION: Understanding the longitudinal trajectories of symptoms in schizophrenia is crucial for optimizing therapeutic strategies and improving patient outcomes. Personalised interventions tailored to individual symptom profiles and early clinical responses are recommended to enhance treatment efficacy and promote recovery. The PANSS scale can be used to delineate Trajectories of various symptom Groups in Schizophrenia.

History of tobacco smoking and alcohol use can predict the effectiveness of electroconvulsive therapy in individuals with schizophrenia: A multicenter clinical trial.

BACKGROUND: Current research has found that factors such as gender, age, and family history can predict the efficacy of electroconvulsive therapy (ECT) in individuals with schizophrenia. In our clinical practice, we anecdotally observed that tobacco smokers and alcohol drinkers with schizophrenia seemed to respond more effectively to ECT than non-smokers and non-drinkers. The current study aimed to examine whether history of tobacco smoking or alcohol consumption serve as indicators for predicting therapeutic efficacy of ECT in individuals with schizophrenia. METHODS: A total of 481 individuals receiving ECT combined with antipsychotic medication (ECT + AP medication) completed a two-week (six sessions of ECT) follow-up; 106 individuals receiving only antipsychotic medication (AP medication) also completed a two-week follow-up. Smoking, alcohol consumption, and AP medication usage was recorded for these individuals. Severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: ECT + AP medication: Compared to schizophrenic individuals without a history of smoking (non-smokers), those with a history of smoking (smokers) showed a high decrease in negative symptoms (36.96% vs 24.76%; F = 5.974, p = 0.015). While, compared to individuals without a history of alcohol consumption (non-drinkers), those with a history of alcohol consumption (drinkers) showed a high decrease in positive symptoms (48.90% vs 41.47%; F = 5.074, p = 0.025). AP medication: No differences were found in symptom reduction between smokers and non-smokers or between drinkers and non-drinkers (p > 0.05). CONCLUSIONS: Smoking history in schizophrenic individuals independently predicts better improvement in negative symptoms after ECT, while alcohol consumption history independently predicts better improvement in positive symptoms after ECT. This is a clinically significant finding.

Neurofeedback technique for treating male schizophrenia patients with impulsive behavior: a randomized controlled study.

Background: Schizophrenia is one of the most severe mental disorders, frequently associated with aggression and violence, particularly in male patients. The underlying mechanisms of violent behavior in these patients remain unclear, limiting effective treatment options and highlighting the need for further research into interventions for impulsive behaviors. This study aims to evaluate the clinical efficacy of neurofeedback treatment in hospitalized male schizophrenia patients exhibiting impulsive behaviors. Methods: The study was designed as a single-center, randomized, single-blind, sham-controlled parallel trial. Eighty patients were randomly assigned to either a study group or a control group. The control group received risperidone and sham neurofeedback, while the study group received risperidone and active neurofeedback therapy. Both groups underwent training five times per week, with each session lasting 20 minutes, over a six-week period. Clinical symptoms were assessed at baseline, three weeks and six weeks using the Positive and Negative Syndrome Scale (PANSS), the Modified Overt Aggression Scale (MOAS), and the Rating Scale for Extrapyramidal Side Effects (RSESE). Statistical analyses were conducted to compare the therapeutic effects between the two groups at the study's conclusion. Results: Initial comparisons showed no significant differences in baseline data, except for the number of prior hospitalizations (P<0.018). By the end of the study, the study group demonstrate significant improvements in MOAS and PANSS scores (including the Excited, Positive, Cognitive, and Depressive/Anxiety Components), with no significant changes in RSESE scores. Discussion: Both time and group interactions were significant across most outcomes, underscoring the efficacy of neurofeedback in reducing the severity of impulsive behaviors and associated schizophrenia symptoms. Clinical trial registration: chictr.org.cn, identifier ChiCTR2200063407.

Sex-dependent association study of complement C4 gene with treatment-resistant schizophrenia and hospitalization frequency.

The complement component 4 (C4) gene, codes for two isotypes, C4A and C4B, and can exist in long or short forms (C4L and C4S). The C4AL variant has been associated with elevated schizophrenia (SCZ) risk. Here, we investigated the relationship between C4 variation and clinical outcomes in SCZ. N = 434 adults with SCZ or schizoaffective disorder were included in this retrospective study. A three-step genotyping workflow was performed to determine C4 copy number variants. These variants were tested for association with clinical outcome measures, including treatment-resistant SCZ (TRS), number of hospitalizations (NOH), and symptom severity (PANSS). Sex and ancestry stratified analyses were performed. We observed a marginally significant association between C4S and TRS in males only, and a negative association between C4S and NOH in the total sample. C4AS had negative association with NOH in males and non-Europeans. Lastly, C4A copy numbers and C4A predicted brain expression showed negative association with NOH in males only. Our study provides further support for sex-specific effect of C4 on SCZ clinical outcomes, and also suggests that C4S and C4AS might have a protective effect against increased severity. C4 could potentially serve as a genetic biomarker in the future, however, more research is required.

Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia.

BACKGROUND: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). METHODS: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). RESULTS: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. CONCLUSIONS: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia.

Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients.

High-Density Lipoprotein Correlates with Cognitive Functioning in Schizophrenic Women.

(1) Background: Schizophrenia is a chronic and progressive neuropsychiatric illness. Apart from positive and negative symptoms, 98% of the population diagnosed with schizophrenia have impaired cognitive functioning, which significantly influences the quality of life. The correlation between lipids and cognitive functioning has been well established. Our study aimed to investigate correlations between cognitive functions, the severity of schizophrenia symptoms, and lipid profiles. (2) Methods: Fifty-two women diagnosed with schizophrenia participated in this study. Cognitive functioning was measured using the Wisconsin Card Sorting Test (WCST). The Positive and Negative Symptom Scale (PANSS) was used. The serum lipid profile, including low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and triglycerides was measured. (3) Results: Better cognitive functions were associated with normal HDL levels, while low HDL levels correlated with worse WSCT scores. Only the PANSS negative subscale showed a correlation with HDL levels. Correlations with chronicity of schizophrenia and the patient's age with poorer cognitive functions, but not with symptom severity, were detected. Early/late age at onset did not influence WSCT scores. (4) Conclusions: Our results suggest high HDL levels might be a protective factor against cognitive impairment. The influences of age and illness duration also play a vital role in cognitive performance.

Measuring the concurrent validity of the norwegian versions of the psychotic symptom rating scales (PSYRATS) and the positive scale from the positive and negative syndrome scale (PANSS).

PURPOSE: The Positive and Negative Syndrome Scale (PANSS) is one of the most commonly used assessment tools for measuring psychotic symptoms. The Psychotic Symptom Rating Scales (PSYRATS) is another instrument created specifically to assess delusions and auditory hallucinations. However, research on the concurrent validity of PSYRATS with PANSS is limited. There are also inconsistent findings regarding the association between the PSYRATS scales and the PANSS positive scale. The present study aims to add to the understanding of the concurrent validity of these measures, while also incorporating a broader measure of psychiatric symptoms (the symptom scale from the Global Assessment of Functioning Scale - split version, GAF-S). MATERIALS AND METHODS: Spearman's Rank Order Correlations (rho) were calculated for scores from the PANSS positive scale, PSYRATS and GAF-S in a sample of 148 participants with psychotic disorders at three time points. RESULTS: The findings indicate concurrent validity between PSYRATS and PANSS, while the PSYRATS scales were not consistently correlated with GAF-S. CONCLUSIONS: PSYRATS may be a valid assessment tool for evaluating psychotic symptoms. The utility of PSYRATS in research and clinical practice should be investigated further.

Exploring the latent cognitive structure in schizophrenia: implications for antipsychotic treatment responses.

BACKGROUND: Individuals diagnosed with schizophrenia present diverse degrees and types of cognitive impairment, leading to variations in responses to antipsychotic treatments. Understanding the underlying cognitive structures is crucial for assessing this heterogeneity. Utilizing latent profile analysis (LPA) enables the delineation of latent categories of cognitive function. Integrating this approach with a dimensional perspective allows for the exploration of the relationship between cognitive function and treatment response. METHODS: This study examined 647 patients from two distinct cohorts. Utilizing LPA within the discovery cohort (n = 333) and the replication cohort (n = 314), latent subtypes were identified categorically. The stability of cognitive structures was evaluated employing Latent Transition Analysis (LTA). The relationship between cognitive function and treatment response were investigated by comparing Positive and Negative Syndrome Scale (PANSS) reduction rates across diverse cognitive subtypes. Furthermore, dimensional insights were gained through correlation analyses between cognitive tests and PANSS reduction rates. RESULTS: In terms of categorical, individuals diagnosed with schizophrenia can be categorized into three distinct subtypes: those 'without cognitive deficit', those 'with mild-moderate cognitive 'eficit', and those 'with moderate-severe cognitive deficit'. There are significant differences in PANSS reduction rates among patients belonging to these subtypes following antipsychotic treatment (p < 0.05). Furthermore, from a dimensional perspective, processing speed at baseline is positively correlated with PANSS score reduction rates at week 8/week 10 (p < 0.01). CONCLUSIONS: Our findings have unveiled the latent subtypes of cognitive function in schizophrenia, illuminating the association between cognitive function and responses to antipsychotic treatment from both categorical and dimensional perspectives.

Assessment of symptom severity in psychotic disorder patients based on heart rate variability and accelerometer mobility data.

BACKGROUND: Advancement in mental health care requires easily accessible, efficient diagnostic and treatment assessment tools. Viable biomarkers could enable objectification and automation of the diagnostic and treatment process, currently dependent on a psychiatric interview. Available wearable technology and computational methods make it possible to incorporate heart rate variability (HRV), an indicator of autonomic nervous system (ANS) activity, into potential diagnostic and treatment assessment frameworks as a biomarker of disease severity in mental disorders, including schizophrenia and bipolar disorder (BD). METHOD: We used a commercially available electrocardiography (ECG) chest strap with a built-in accelerometer, i.e. Polar H10, to record R-R intervals and physical activity of 30 hospitalized schizophrenia or BD patients and 30 control participants through ca. 1.5-2 h time periods. We validated a novel approach to data acquisition based on a flexible, patient-friendly and cost-effective setting. We analyzed the relationship between HRV and the Positive and Negative Syndrome Scale (PANSS) test scores, as well as the HRV and mobility coefficient. We also proposed a method of rest period selection based on R-R intervals and mobility data. The source code for reproducing all experiments is available on GitHub, while the dataset is published on Zenodo. RESULTS: Mean HRV values were lower in the patient compared to the control group and negatively correlated with the results of the PANSS general subcategory. For the control group, we also discovered the inversely proportional dependency between the mobility coefficient, based on accelerometer data, and HRV. This relationship was less pronounced for the treatment group. CONCLUSIONS: HRV value itself, as well as the relationship between HRV and mobility, may be promising biomarkers in disease diagnostics. These findings can be used to develop a flexible monitoring system for symptom severity assessment.

Pharmacogenetic intervention improves treatment outcomes in Chinese adult men with schizophrenia.

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

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders.

BACKGROUND: Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. METHODS: The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. RESULTS: The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. CONCLUSIONS: In our study, patients with schizophrenia - including the drug-naïve - have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study.

BACKGROUND: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. METHODS: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. RESULTS: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. CONCLUSIONS: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.

Prodromal period of psychosis: diagnostic criteria.

OBJECTIVE: Aim: To study the psychopathological mechanisms of the development of the prodromal stage of psychosis in order to identify risk factors for the formation of psychosis. PATIENTS AND METHODS: Materials and Methods: In this research 137 patients with newly diagnosed psychosis were examined: 65 patients with a diagnosis of paranoid schizophrenia; 72 patients - with a diagnosis of acute polymorphic psychotic disorder. RESULTS: Results: According to the analysis of symptoms using the PANSS, the absence of signs of an anxious state, conceptual disorganization of thinking, emotional withdrowal are reliable signs of PPP in PS, and unusual thought content, absence of signs of stereotyped thinking, tension, anxiety, and hallucinations are reliable signs of PPP in APPD. According to the analysis of symptoms using the SOPS, unusual thought content/delusional ideas, bizarre thinking, social anhedonia, suspiciousness/persecutory ideas, decrease in expressiveness of emotions are reliable signs of PPP in PS, and bizarre thinking, impaired tolerance to normal stress, sleep disturbance, perceptual abnormalities/hallucinations, trouble with focus and attention are reliable signs of PPP in APPD. CONCLUSION: Conclusions: In the process of studying the clinical-psychopathological and pathopsychological aspects of the development of the PPP, a number of risk factors for the formation of psychosis were identified. We found that he most important diagnostic signs of PPP in PS patients are: stereotyped thinking, social isolation, disorganizational thinking disorders, passive-apathetic social detachment, suspiciousness. The most informative prodromal symptoms of HP in PS patients are: conceptual disorganization of thinking, bizzare thinking, social isolation, suspiciousness/persecutory ideas, reduced expression of emotions.

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

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

Cognitive Inflexibility Predicts Negative Symptoms Severity in Patients with First-Episode Psychosis: A 1-Year Follow-Up Study.

Negative symptoms and cognitive deficits play a major role in psychosis and significantly influence the functional outcomes of patients, particularly those with a first episode of psychosis (FEP). However, limited research has explored the predictive capacity of cognitive deficits during FEP for subsequent negative symptomatology. Drawing from the Athens FEP research study, we conducted a retrospective longitudinal study in 80 individuals with FEP. All patients were drug naive at admission. Cognitive tests were administered at 1-month and 1-year post-admission, while negative symptomatology was assessed at the same time points using PANSS by trained raters. We considered confounding factors such as age, gender, duration of untreated psychosis (DUP), treatment received, premorbid social adjustment, and premorbid IQ. Univariate regression analysis identified cognitive domains that correlated with negative symptomatology. These, along with the confounders, were incorporated into a multiple regression, with the 1-year PANSS negative scale serving as the dependent variable. Employing the backward elimination technique, we found a statistically significant inverse relationship between the categories completed in the Wisconsin card sorting test (WCST) and the 1-year PANNS negative scale (p = 0.01), beyond the associations with DUP and the 1-month PANSS negative scale. Our results suggest that cognitive flexibility, a key component of executive functions, predicts negative symptom severity one year after FEP.