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.

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.

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.

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.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 (≤24 weeks and >24 weeks). There was also no statistical difference in drop-out rates between the two groups. CONCLUSION: For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.

Diagnostic value and role of serum miR-15a-5p in patients with schizophrenia.

BACKGROUND: More and more studies have confirmed that the heredity plays an important role in mental disorders, especially microRNA. The objective of this research was to explore the level of miR-15a-5p in patients with schizophrenia (SZ), and to evaluate the feasibility of this miRNA as a diagnostic marker of SZ. METHODS: The serum level of miR-15a-5p in patients with SZ and healthy people was detected by RT-qPCR. ROC curve was established to evaluate the clinical diagnostic significance of miR-15a-5p in SZ. Pearson correlation coefficient was used to evaluate the correlation between miR-15a-5p level and PANSS score. Logistic regression was used to assess the risk factors of SZ. A rat model of SZ was established, and the effects of miR-15a-5p on the behavior of SZ rats were observed through water maze test and open field test. RESULTS: The serum level of miR-15a-5p in patients with SZ was significantly increased, and ROC analysis revealed that miR-15a-5p had clinical diagnostic value in SZ. High level of miR-15a-5p was positively correlated with the positive symptom, negative symptom and general psychopathology subscore of patients. Logistic regression results showed that miR-15a-5p was a risk factor affecting the occurrence of SZ. Animal studies showed that the serum level of miR-15a-5p was elevated in the SZ rats, and inhibiting the expression of miR-15a-5p has a positive effect on improving the cognitive function and anxiety behavior of SZ rats. CONCLUSIONS: Serum miR-15a-5p is a risk factor for SZ, which is of great significance for the diagnosis of SZ.

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.

Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population.

Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson's correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.

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.

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.

Relationships Between Adherence to Guideline Recommendations for Pharmacological Therapy Among Clinicians and Psychotic Symptoms in Patients With Schizophrenia.

BACKGROUND: Clinician adherence to guideline recommendations in the pharmacological therapy of schizophrenia is important for favorable patient outcomes. To evaluate whether prescriptions followed the guidelines for pharmacological therapy of schizophrenia, we recently developed a summary indicator of multiple quality indicators: the individual fitness score (IFS). It is unclear whether adherence to the guidelines is related to patient outcomes. Here, we investigated correlations between the IFS values and psychotic symptoms in patients with schizophrenia. METHODS: We assessed whether patients' current prescriptions adhered to the guideline recommendations using the IFS in 47 patients with treatment-resistant schizophrenia (TRS) and 353 patients with non-TRS (total n = 400), respectively. We investigated correlations between the IFS and total scores and scores on the 5 subscales of the Positive and Negative Syndrome Scale (PANSS). Furthermore, we explored correlations between over 2-year longitudinal changes in IFS values and changes in psychotic symptoms in some patients (n = 77). RESULTS: We found significant negative correlation between the IFS and PANSS total score in all patients with schizophrenia (ß = -0.18, P = 9.80 × 10-5). The IFS was significantly and nominally negatively correlated with the PANSS total score in patients with non-TRS (Spearman's rho = -0.15, P = 4.40 × 10-3) and patients with TRS (rho = -0.37, P = .011), respectively. The IFS was also significantly and nominally negatively correlated with several factors, such as the negative and depressed factors, in patients with non-TRS and patients with TRS, respectively (P < .05). Furthermore, the change in IFS values was marginally negatively correlated with the changes in PANSS total scores and scores on the positive and depressed factors (P < .05). CONCLUSIONS: These findings suggest that efforts to improve clinician adherence to guideline recommendations for pharmacological therapy of schizophrenia, as assessed by the IFS, may lead to better outcomes in patients with schizophrenia.

Amygdala signal abnormality and cognitive impairment in drug-naïve schizophrenia.

BACKGROUND: Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study. METHODS: We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People's Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC's amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS. RESULTS: (1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p < 0.001), and the Fractional amplitude of low-frequency fluctuations (FALFF) values of bilateral amygdala increased (tL=3.916, p < 0.001; tR=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p < 0.001; rR=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively. CONCLUSION: The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.

Abnormalities of the Amygdala in schizophrenia: a real world study.

BACKGROUND: Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area. METHODS: We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People's Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment. RESULTS: Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p' = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover. CONCLUSION: There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.

Do symptoms moderate the association between participation and executive functions outcomes among people with schizophrenia?

BACKGROUND: Literature explains participation limitations among people with schizophrenia through the context of metacognitive limitations, specifically in symptoms and in executive functions (EF). Research has shown mixed results regarding associations between symptoms and participation, reporting association with negative symptoms, positive symptoms, or only metacognitive limitations. The aim of this study was to deepen understanding of the symptoms' impact on the association between participation and executive function among people with schizophrenia. METHODS: Forty-three participants with schizophrenia received 8 group sessions of focused metacognitive intervention (MCG) aimed at promoting participation by focusing on EF components (e.g., analyzing individual cognitive strategy use). Three measures were administered: the Positive and Negative Syndrome Scale (PANSS) to evaluate symptoms, the Weekly Calendar Planning Assessment (WCPA) to assess EF, and the Activity Card Sort (ACS) to measure participation at the baseline and 12 weeks following completion of the intervention. Scores were compared to a matched control group of 41 people with schizophrenia who instead received treatment as usual. The role of PANSS as moderator was examined using multiple hierarchical regressions, entering interactions between the PANSS scores and WCPA change scores in the final regression step. RESULTS: Relationships were not significant for participants with high PANSS scores. A positive relationship existed between change in WCPA and change in ACS for participants with low PANSS scores. CONCLUSIONS: These results demonstrate that low PANSS scores moderate the association between EF and participation and highlight the importance of symptoms as a predictor of participation following the MCG intervention. TRIAL REGISTRATION: The trial was retrospectively registered at clinical. TRIAL: gov. CLINICALTRIALS: gov Identifier: NCT05556941. Clinicaltrial.gov registration date: 27/09/2022.

Symptoms and functioning: a content analysis of the PANSS under the ICF framework.

PURPOSE: The study aimed to compare the content of the Positive and Negative Syndrome Scale (PANSS) with that of the International Classification of Functioning, Disability, and Health (ICF) and to examine the extent to which PANSS items are represented in the ICF Core Sets (ICF-CS) for schizophrenia. METHODS: The 30 items of the PANSS were linked to the ICF using established rules by two health professionals experienced in applying the ICF conceptual framework. RESULTS: PANSS items were linked to 42 unique ICF categories, corresponding mainly to the Body functions component; categories b160 Thought functions and b152 Emotional functions from this component were the most frequently linked. Regarding the Activities and participation component, the second-level category d720 Complex interpersonal interactions was the most frequently linked to PANSS items. Overall, PANSS items covered 18% and 40% of the categories included, respectively, in the Comprehensive and Brief versions of the ICF-CSs for schizophrenia. No PANSS items were linked to categories from the Body structures or Environmental factors components. CONCLUSIONS: The PANSS broadly covers the content of the ICF, especially as regards mental and movement-related functions, although it also covers some aspects of interpersonal relationships.

SYMPTOM SEVERITY IN SCHIZOPHRENIA PATIENTS WITH NPAS3, DYSBINDIN-1 AND/OR TRIOBP PROTEIN PATHOLOGY IN THEIR BLOOD SERUM: A PANSS-BASED FOLLOW UP STUDY.

BACKGROUND: It has been proposed that aggregation of specific proteins in the brain may be a pathological element in schizophrenia and other chronic disorders. Multiple such aggregating proteins have now been implicated through post mortem investigation, including NPAS3 (Neuronal PAS domain protein 3), dysbindin-1 (encoded by the DTNBP1, Dystrobrevin Binding Protein 1, gene) and TRIOBP (Trio-Binding Protein, multiple isoforms). While the presence of protein aggregates in the brain is interesting in terms of understanding pathology, it is impractical as a biomarker. These proteins were therefore investigated recently in blood serum of schizophrenia patients and controls, showing patients to have higher levels of NPAS3 in their serum generally. TRIOBP-1 and dysbindin-1 were also found in an insoluble state, implying aggregation, but did not clearly corresponding to disease state. SUBJECT AND METHODS: We revisit 47 of the originally recruited 50 patients with schizophrenia, all of whom are Croatian and aged between 18 and 72. We assessed their symptom specificity and severity using PANSS (the Positive and Negative Symptoms Scale), comparing those with NPAS3, insoluble dysbindin-1 and/or insoluble TRIOBP-1 in their blood serum to those lacking any such protein dysregulation. RESULTS: The frequency of each individual potential protein pathology among these patients was too low for meaningful statistical analysis, however the 11 patients that displayed one or more of these pathologies (NPAS3, dysbindin-1, TRIOBP-1 and/or TRIOBP-5/6) showed a subtle but significant increase in total PANSS scores compared to the 36 patients displaying none of the pathologies (p = 0.031), seemingly driven principally by increased scores on the general psychopathology scale. CONCLUSION: While the numbers of patients involved do not allow firm conclusions to be drawn at this time, this provides the first indication that disturbed proteostasis in blood serum, of proteins that aggregate in the brains of schizophrenia patients, may correlate with the severity of schizophrenia symptoms.

Longitudinal study of the course and outcome of first-episode psychosis.

Background: Study of first episode psychosis (FEP), an episode of psychotic nature, which manifests for the first time in an individual in the longitudinal continuum of his/her illness, has been a matter of research interest in recent years, as this may give more insight to the overall phenomenology and course of psychotic illnesses. Methods: A study was undertaken to evaluate course and outcome of first episode psychosis. A total of 100 consecutive inpatients were selected for the study. Informed consent was obtained. Structured Proforma was used for recording psychosocial profiles and relevant medical history. Brief Psychiatric Rating Scale (BPRS) was given to assess the severity of psychopathology; Positive and Negative Symptom Scale (PANSS) to assess the severity of psychosis; Becks Suicidal Ideation Scale (BSI) to assess the extent of suicidality and Global Assessment of Functioning (GAF) to assess global functioning of the individual. The assessment was done at baseline, at six months, and at one year. Results: First episode psychosis constituted around a tenth of the caseload. It commonly affected people in the third decade of life. There was an improvement in 92% of the cases over a year of study. Schizophrenia constituted the majority of first episode psychosis. The history of smoking was relatively higher in acute and transient psychotic disorders. Age inversely correlated with the severity of psychopathology. There was no difference in improvement in psychopathology over time in patients of schizophrenia and related disorder vis--vis other psychotic disorders. Conclusion: Our study did not find any significantly varied sociodemographic factors in the course and outcome of the illness. It also refuted the schism between various types of psychosis based on the current classificatory system. It draws our attention toward the unitary concept of psychosis and is a call to re-think our strategies in the management of psychosis.

Multimodal brain deficits shared in early-onset and adult-onset schizophrenia predict positive symptoms regardless of illness stage.

Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early-onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early-onset (EOS) and adult-onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co-varying patterns by jointly analyzing three MRI features: fractional amplitude of low-frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug-naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub-cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug-naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug-naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.

Impaired insight in schizophrenia: impact on patient-reported and physician-reported outcome measures in a randomized controlled trial.

BACKGROUND: Impaired insight poses a challenge in the treatment of patients with schizophrenia because of its potential to jeopardize therapeutic engagement and medication adherence. This study explored how insight impairment, graded from none to extreme, is related to patient-reported mental health status, depression, and neurocognition in schizophrenia. METHODS: In a post hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study (NCT00014001), insight was measured using the Positive and Negative Syndrome Scale (PANSS) Item G12 (lack of insight). Additional assessments for this analysis included the 12-Item Short-Form Health Survey (SF-12) Mental Component Summary (MCS), physician- and patient-reported Clinical Global Impression-Severity (CGI-S), MATRICS Consensus Cognitive Battery, and Calgary Depression Scale for Schizophrenia. Relationships between patient-reported outcomes and PANSS total and Item G12 ratings were evaluated. RESULTS: Among 1431 CATIE study participants in this analysis, increasingly impaired insight at baseline was significantly associated with better patient-reported quality of life (QoL), lower baseline depression, and greater divergence between physician- and patient-reported illness severity. Patients with more severely impaired insight reported milder illness compared with physician reports, particularly those with moderate-severe to extreme impairment (PANSS Item G12 rating ≥ 5), approximately 10% (138/1431) of CATIE participants. For the 90% of patients with PANSS Item G12 ratings < 5, patient-reported QoL decreased with increasing symptoms. SF-12 MCS scores were linearly related to baseline PANSS total score only in patients with PANSS total score < 90 (moderately ill or better), and better symptom scores were associated with higher QoL. No significant relationship between insight and neurocognition was observed. CONCLUSIONS: In the small subgroup (10%) of CATIE study patients with schizophrenia and PANSS Item G12 ratings ≥5, moderate-severe-severe/extreme insight impairment was associated with significantly more positive perception of QoL and illness severity by the patient versus the treating physician. This was not observed in the remaining 90% of patients with normal to moderately impaired insight, suggesting that poor insight as a threat to the validity of self-report is uncommon.

Positive and negative syndrome scale in forensic patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Among forensic patients with schizophrenia spectrum disorders, the association between symptomatology and violence is still not entirely clear in literature, especially because symptoms shift both during the acute phase of the illness and after. The aims were to investigate the level of symptomatology in forensic patients and to evaluate if there are differences in the level of symptoms between forensic and non-forensic patients. According to PRISMA guidelines, a systematic search was performed in PubMed, Web of Science, and ProQuest, using the following key words: "forensic" AND "Positive and Negative Syndrome Scale" OR "PANSS". A total of 27 studies were included in the systematic review, while only 23 studies in the meta-analysis. The overall sample included a total of 1702 participants, most commonly male and inpatients in forensic settings. We found that studies with an entirely male sample had significantly lower Positive PANSS ratings than studies with mixed samples. Although both forensic and non-forensic patients were affected by mild psychopathological symptoms, forensic patients presented higher ratings in all four PANSS scales. This meta-analysis shows that forensic patients reported a mild level of symptomatology, as assessed with the PANSS, and therefore might be considered as patients in partial remission. Among patients with schizophrenia, the association between symptoms and violence is very complex: many factors might be considered as key mediators and thus should be taken into account to explain this association. Further studies are needed.Trial registration all materials and data can be found on the OSF framework: https://osf.io/5ceja (date of registration: 8 September 2021).