Positive and negative schizotypy personality traits are lower in individuals on ketogenic diet in a non-clinical sample.

Schizotypal personality comprises traits such as odd beliefs, perceptual abnormalities, and social difficulties; these traits are distributed throughout the general population. While not meeting the clinical threshold for schizophrenia or schizotypal personality disorder, schizotypal personality traits still provide insights for understanding early clinical risk factors. Ketogenic diet reportedly reduces psychotic symptoms in preclinical and clinical studies. Therefore, we investigated whether ketogenic diet is associated with lower schizotypal traits in the general population. Participants following a ketogenic or other diet were recruited using opportunity sampling. Individuals completed a survey investigating general demographic, socioeconomic, health, diet and lifestyle questions, followed by the Schizotypal Personality Questionnaire - Brief Revised version (SPQ-BR). We found that individuals following a ketogenic diet (n = 118) had lower ideas of reference, magical thinking, suspiciousness, unusual perceptions, constricted affect, social anxiety scores, cognitive (positive) perceptual scores, interpersonal (negative) scores and total SPQ-BR compared to individuals on the other diets (n = 139). Magical thinking, constricted affect, social anxiety, cognitive perceptual, interpersonal scores and total SPQ-BR scores remained significant when we controlled for body mass index (BMI) and age. Disorganised features were not influenced by ketogenic diet. The longer individuals adhered to a ketogenic diet the lower their positive and negative schizotypy traits. These findings highlight that ketogenic diet is associated with lower non-clinical schizotypal personality traits. Our results suggest that ketogenic diet might have potential prophylactic properties for individuals at-risk for psychosis.

A comparison of clinical characteristics and course predictors in early- and childhood-onset schizophrenia.

AIM: The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis. METHODS: Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. RESULTS: A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course. CONCLUSION: Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families.

Trustworthiness judgments and pupil-size in individuals with schizophrenia.

Individuals with schizophrenia show aberrant processing of social cues. In the current study, we (1) compared trustworthiness ratings of faces between patients with schizophrenia and healthy controls, (2) compared pupillary reactivity between patients and controls (3) examined whether trustworthiness judgments in schizophrenia are related to pupil reactivity, (4) and examined associations between trustworthiness judgements and symptom severity, specifically paranoia. Patients with schizophrenia spectrum disorders (N = 48) and healthy controls (N = 33) completed a Trustworthiness Task, during which their pupil size was measured via an eye-tracking device. The mean baseline-corrected pupil size was calculated from 24 pictures of real neutral faces, each presented for 2500ms. Self-reported psychotic experiences were measured by Community Assessment of Psychic Functioning (CAPE-42), and symptom severity was rated by Brief Psychiatric Rating Scale (BPRS). No group differences were found in trustworthiness ratings or pupil reactivity parameters during trustworthiness judgments. Separately, among patients, absolute difference in pupil-size change and dilation after reaching minimum size were related to more severe positive symptoms and self-reported paranoia. Our results did not show social cognitive biases in the stable outpatients with schizophrenia, or the role of pupil reactivity in trustworthiness judgments. Future studies should use longer stimuli for pupillary reactivity and control the type and dosage of utilized antipsychotic medication. Further studies are required to explore relationships in larger and more symptomatic groups of patients.

A deep learning approach for diagnosis of schizophrenia disorder via data augmentation based on convolutional neural network and long short-term memory.

Schizophrenia (SZ) is a severe, chronic mental disorder without specific treatment. Due to the increasing prevalence of SZ in societies and the similarity of the characteristics of this disease with other mental illnesses such as bipolar disorder, most people are not aware of having it in their daily lives. Therefore, early detection of this disease will allow the sufferer to seek treatment or at least control it. Previous SZ detection studies through machine learning methods, require the extraction and selection of features before the classification process. This study attempts to develop a novel, end-to-end approach based on a 15-layers convolutional neural network (CNN) and a 16-layers CNN- long short-term memory (LSTM) to help psychiatrists automatically diagnose SZ from electroencephalogram (EEG) signals. The deep model uses CNN layers to learn the temporal properties of the signals, while LSTM layers provide the sequence learning mechanism. Also, data augmentation method based on generative adversarial networks is employed over the training set to increase the diversity of the data. Results on a large EEG dataset show the high diagnostic potential of both proposed methods, achieving remarkable accuracy of 98% and 99%. This study shows that the proposed framework is able to accurately discriminate SZ from healthy subject and is potentially useful for developing diagnostic tools for SZ disorder.

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.

Exploring the interplay of psychiatric symptoms, antipsychotic medications, side effects, employment status, and quality of life in Chronic Schizophrenia.

BACKGROUND: Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients. METHODS: The QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications. RESULTS: We recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P < 0.005). Patients who were taking activating second-generation antipsychotics (SGAs) had lower scores on total SQLS, Motivation/ Energy domain of SQLS (SQLS-ME) as well as Symptoms/ Side effects domain of SQLS (SQLS-SS) compared to those taking non-activating SGAs (all P < 0.005). Multiple regression analysis showed that depressive/ anxiety symptoms and cognitive impairment had significant negative effects on QoL (P ≤ 0.001), while activating SGAs had a positive effect (P < 0.005). Blunted affect and unemployment were inversely associated with the motivation/energy domain (P < 0.001). CONCLUSION: Our findings emphasize the important role of depression/anxiety symptoms and cognitive impairment in the QoL of patients with chronic schizophrenia. Activating SGAs and employment may improve the QoL of these individuals. TRIAL REGISTRATION: This protocol was registered at chictr.org.cn (Identifier: ChiCTR2100043537).

Divergent thinking as a predictor of life skills in patients with schizophrenia: Evidence from the modified Tinkertoy Test.

Aim: Patients with schizophrenia often exhibit poor life skills, posing significant clinical challenges. Life skills comprise cognitive functions crucial for planning daily activities, including divergent thinking. However, the cognitive deficits contributing to these diminished skills among patients with schizophrenia are underexplored. This study introduces a modified Tinkertoy Test (m-TTT) to investigate the correlation between life skills, divergent thinking, and psychological assessment tools in patients with schizophrenia. Methods: Fifty-two patients with schizophrenia, alongside a control group, matched for sex, age, and education, were evaluated using psychological assessment tools. For the patient group, the Life Skills Profile (LSP) and Positive and Negative Syndrome Scale were administered to measure functional abilities and psychiatric symptoms, respectively. Additionally, duration of disease and antipsychotic daily dosage levels were assessed exclusively in the patient group. Both groups were evaluated with the m-TTT, Idea Fluency Test (IFT), Design Fluency Test (DFT), and Brief Assessment of Cognition in Schizophrenia (BACS) to comprehensively assess cognitive functions. A stepwise multiple regression model was conducted to identify significant correlates of LSP total score among the patient group. Results: The schizophrenia group scored notably lower than the neurotypical controls on the m-TTT, IFT, DFT, and BACS. Our stepwise multiple regression analysis highlighted that the LSP total score was significantly correlated with the total m-TTT score and presence of negative symptoms. Conclusion: Divergent thinking could be a crucial factor in the life skills of individuals with schizophrenia. Rehabilitation programs based on this cognitive function might enhance their daily living capabilities.

Comparative effectiveness of clozapine and non-clozapine atypical antipsychotics provided by the Brazilian National Health System in adults with schizophrenia.

Introduction: Currently, 21 million people live with the disease, mostly in low to middle-income countries. We aimed to assess the survival of patients with schizophrenia using clozapine compared with non-clozapine atypical antipsychotics provided by the Brazilian National Health System using real-world data. Materials and methods: This is an open retrospective cohort study of patients diagnosed with schizophrenia to whom atypical antipsychotics were dispensed by the Brazilian National Health System between 2000 and 2015, based on deterministic-probabilistic pairing of administrative data records. The Kaplan-Meier method was used to estimate the cumulative probability of survival and the Cox proportional hazards model was adjusted to assess the risk factors for survival via the hazard ratio (HR). Result: Participants were 375,352 adults with schizophrenia, with an overall survival rate of 76.0% (95%CI 75.0-76.0) at the end of the cohort. Multivariate analysis indicated a greater risk of death for men (HR=1.30; 95%CI 1.27-1.32), older adults (HR=17.05; 95%CI 16.52-17.60), and in the Southeast region of Brazil (HR=1.20; 95%CI 1.17-1.23). Patients who used non-clozapine atypical antipsychotics had a 21% greater risk of death when compared to those taking clozapine (HR=1.21; 95%CI 1.14-1.29). Additionally, a history of hospitalization for pneumonia (HR=2.17; 95%CI 2.11-2.23) was the main clinical variable associated with increased risk of death, followed by hospitalization for lung cancer (HR=1.82; 95%CI 1.58-2.08), cardiovascular diseases (HR=1.44; 95%CI 1.40-1.49) and any type of neoplasia (HR=1.29; 95%CI 1.19-1.40). Discussion: This is the first published Brazilian cohort study that evaluated survival in people with schizophrenia, highlighting the impact of atypical antipsychotics. In this real-world analysis, the use of clozapine had a protective effect on survival when compared to olanzapine, risperidone, quetiapine, and ziprasidone.

Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Study of the genetic association between selected 3q29 region genes and schizophrenia and autism spectrum disorder in the Japanese population.

Psychiatric disorders are highly inheritable, and most psychiatric disorders exhibit genetic overlap. Recent studies associated the 3q29 recurrent deletion with schizophrenia (SCZ) and autism spectrum disorder (ASD). In this study, we investigated the association of genes in the 3q29 region with SCZ and ASD. TM4SF19 and PAK2 were chosen as candidate genes for this study based on evidence from previous research. We sequenced TM4SF19 and PAK2 in 437 SCZ cases, 187 ASD cases and 524 controls in the Japanese population. Through targeted sequencing, we identified 6 missense variants among the cases (ASD & SCZ), 3 missense variants among controls, and 1 variant common to both cases and controls; however, no loss-of-function variants were identified. Fisher's exact test showed a significant association of variants in TM4SF19 among cases (p=0.0160). These results suggest TM4SF19 variants affect the etiology of SCZ and ASD in the Japanese population. Further research examining 3q29 region genes and their association with SCZ and ASD is thus needed.

Caregiver burden and its sociodemographic determinants in family caregivers of patients with schizophrenia attending a psychiatric tertiary hospital in South Africa.

Background: Chronic mental illnesses such as schizophrenia affect patients' functioning, making caregiving necessary although burdensome. Aim: This study aimed to determine caregiver burden and its sociodemographic determinants in family caregivers of patients with schizophrenia attending a Psychiatric Outpatient Department (POD). Setting: Tertiary hospital in Northern Pretoria, South Africa. Methods: In this cross-sectional study conducted over 3 months, 300 consecutive family caregivers who attended the POD were administered a 22-item Zarit Burden Interview (ZBI-22), which has a score of 0-88, with higher values indicating more burden. Their sociodemographic characteristics were ascertained. Linear and ordinal logistic regression analyses were performed to identify determinants or predictors of total and severe burdens, respectively. Results: Most caregivers were aged 46.0 ± 14 years, females (62%), parents (39%), of low-income status (93.7%), had secondary education (70%), resided with the patient (87%), and helped with all troublesome activities (95.3%). The median ZBI-22 score was 19.0 (interquartile range: 13.0-30.5). The determinants of both total and severe burdens were: caregiver age ≥ 50 years adjusted odds ratio (aOR): 2.55, confidence interval (CI): 1.49-4.36; residential area farther away from the hospital aOR: 1.76, CI: 1.3-2.99; increasing months of caregiving aOR: 1.0, CI: 1.001-1.009, p = 0.006; and not having another family member that needs care aOR: 0.43, CI: 0.24-0.78. Conclusion: Having mental healthcare facilities close to residential areas and assisting caregivers aged ≥ 50 years who have multiple family members who need care may alleviate the burden. Contribution: Predicting total and severe caregiver burdens contemporaneously is effective for identifying potential burden interventions.

Psychosis Associated With Hyperglycemia in a Female Patient With Type 1 Diabetes Mellitus: A Case Report.

This paper presents the case of a 22-year-old woman who was hospitalized multiple times with episodes of psychosis co-occurring with hyperglycemia. Her psychosis was characterized by auditory hallucinations, visual hallucinations, and disorganized speech and behavior. The patient has a prior medical history of type 1 diabetes mellitus (T1DM) and Graves' disease and was non-adherent to diabetic diet and medications. The patient is a Somalian refugee who moved to the United States (US) a year ago. We explore the relatively unique observation of hyperglycemia-induced psychosis in the patient, specifically in the context of autoimmune disorders. We also discuss some of the complexities associated with the cultural aspects of mental health and diabetes management in refugee communities and their implications in clinical practice.

Multi-omics analysis reveals the impact of gut microbiota on antipsychotic-induced weight gain in schizophrenia.

Emerging evidence indicates that gut microbial dysbiosis is associated with the development of antipsychotic-induced weight gain in schizophrenia (SZ). However, the exact taxonomic composition and functionality that constitute the "obesogenic" microbial profile remain elusive. Our retrospective survey identified two groups of the SZ population separated by BMI, with 1/3 of patients developing overweight/obesity after chronic antipsychotic treatment. Based on multi-omics analysis, we observed altered gut microbiota in SZ patients with overweight/obesity, characterized by a reduction in several beneficial bacteria genera, including Bacteroides, Parabacteroides, Akkermansia, and Clostridium. This microbial dysbiosis was accompanied by disrupted energy expenditure and nutritional metabolism, worsened metabolic indices, and reduced levels of beneficial metabolites, e.g. indole-3-carboxylic acid and propionic acid. Moreover, leveraging data from first-episode drug-naïve schizophrenia (FSZ) patients at one-month and one-year follow-up, both artificial neural network and random forest classifier-based prediction models demonstrated a strong ability of microbial profiles to predict antipsychotic-induced weight gain. Importantly, FSZ patients with higher relative abundance of Parabacteria distasonis were less susceptible to antipsychotic-induced weight gain. Thus, gut microbiota could serve as a noninvasive approach to predict antipsychotic-induced weight gain, guiding clinical antipsychotics administration and developing novel therapeutic strategies for weight management in SZ.

Functioning in schizophrenia: Recommendations of an expert panel.

Functioning is a fundamental dimension across all aspects of life, frequently compromised or reduced in individuals with schizophrenia. However, the lack of a commonly agreed definition of functioning in schizophrenia makes it difficult to apply this concept in clinical practice. In this document, we make a detailed analysis of the literature to identify and define functioning and describe how it can be used in clinical practice today. We performed a preliminary literature search in the MEDLINE database (via PubMed) for articles discussing functioning in schizophrenia. The articles retrieved were then read and discussed by a panel of psychiatrists specialising in schizophrenia. The conclusions reached in this meeting formed the basis for a new exhaustive literature search for the purpose of synthesising the evidence published in the past 5 years. In this article, we show the importance a comprehensive, modern, homogeneous definition of functioning in schizophrenia, propose a definition of functioning, and put forward a series of recommendations for assessing functioning in clinical practice. We also review current unmet needs and highlight the need for a standardised tool for evaluating functioning.

Effect of personality traits, psychological resilience and life adversities on lifetime violence trajectories: A novel classification model in schizophrenia.

The risk of violence is higher in schizophrenia spectrum disorders (SSD) compared to the general population and it is a pressing and understudied issue. Several dispositional and environmental factors have been previously correlated with violence, however, there has been little success in assessing their ability to predict violence patterns across the life span. This study aims to assess violence prediction based on personality traits, psychological resilience, and life-course adversities in a non-forensic population of SSD patients. In a sample of 231 patients with SSD, we assessed violence using the Brown-Goodwin History of Lifetime Aggression Scale and conducted cross-sectional assessments of possible predictors such as childhood trauma, personality traits and resilience scores. We then utilized a logistic regression classification algorithm to predict different violence trajectories based on the proposed risk factors. Our model significantly predicted individuals with violence in both childhood and adulthood, as well as childhood-only violence (p < 0.001). However, the model did not show significance for adult-only violence (p = 0.604). In all given trajectories, female sex appeared to be protective against violence, while stressful life events appeared to contribute to it. These results suggest that distinct factors can better inform risk assessment of lifespan violence patterns for personalized interventions in SSD.

Shared Genetic Architecture Among Gastrointestinal Diseases, Schizophrenia, and Brain Subcortical Volumes.

BACKGROUND AND HYPOTHESIS: The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. STUDY DESIGN: Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. STUDY RESULTS: The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. CONCLUSIONS: These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases.

Exposure-Response Modeling in Adults and Adolescents With Schizophrenia to Support the Extrapolation of Brexpiprazole Efficacy to Adolescents.

In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence-based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady-state concentration)-response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure-response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease-drug-dropout models were developed using patient-level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure-response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure-response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13-17 years with schizophrenia.