Perinatal and neonatal factors and mental disorders in children and adolescents: looking for the contributions of the early environment to common and dissociable aspects of psychopathology.

High rates of co-occurrence of mental disorders have been hypothesized to represent a result of common susceptibility to overall psychopathology. The purpose of this study is to test the hypothesis that commonalities among psychiatric disorders might be partially driven by sharable perinatal and neonatal environmental factors for mental disorders. Participants were 6-14 years of age children and their parents. Primary caregivers provided data on perinatal and neonatal information assessed retrospectively (n = 2231). Psychiatric disorders diagnoses were assessed using the Development and Well Being Behavior Assessment (DAWBA). We used bifactor models to disentangle common from dissociable aspects of psychopathology. These models allow modeling psychiatric disorders as the result of a common domain of psychopathology (p-factor) and three dissociable domains (fear, distress, and externalizing symptoms). Associations were tested using linear and tobit regression models. The p-factor was associated with male sex, low socioeconomic status, gestational smoking, gestational drinking, low levels of maternal education and presence of mental disorder in the mother. Associations with specific factors also emerged suggesting some risk factors might also have some role for fear, distress and externalizing factors. Our study supports the hypothesis that overall susceptibility to psychopathology might be partially driven by sharable perinatal and neonatal factors.

Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention. Registration number: PROSPERO CRD42018092033.

Social cognition in individuals with schizophrenia, autism spectrum disorder and controls / Cognição social em indivíduos saudáveis, com esquizofrenia e com transtorno do espectro do autismo

ABSTRACT Objective: The aim of this study was to compare the social cognition profiles of male adults with ASD (n = 15), SCHZ (n = 16) and controls (n = 20). Change the second sentence of the abstract. Methods: A cross-sectional assessment of social cognition domains with emotional face perception with eye tracking was performed, and two IQ measures (Verbal IQ and Performance IQ) (Wechsler Adult Intelligence Scale), and the DSM-IV Structured Clinical Interview were applied. Results: There were no significant differences in terms of average performance in social cognition tests or eye tracking tasks between the ASD and SCHZ groups. However, both had lower performances in most cases when compared to the control group. In the social cognition tasks, individuals in the control group performed better than both clinical groups. Conclusion: Although differences were identified between individuals with ASD and SCHZ, it was not possible to determine patterns or to differentiate the clinical groups.

RESUMO Objetivo: O objetivo deste estudo foi comparar os perfis de cognição social de adultos do sexo masculino com TEA (n = 15), SCHZ (n = 16) e controles (n = 20). Métodos: Foram aplicadas uma avaliação transversal dos domínios de cognição social com percepção emocional com rastreamento ocular, duas medidas de QI (QI verbal e QI de desempenho) (Escala de Inteligência Adulta de Wechsler) e a Entrevista Clínica Estruturada DSM-IV. Resultados: Não houve diferenças significativas em termos de desempenho médio em testes de cognição social ou tarefas de rastreamento ocular entre os grupos ASD e SCHZ. No entanto, ambos tiveram desempenhos mais baixos na maioria dos casos, quando comparados ao grupo controle. Nas tarefas de cognição social, os indivíduos do grupo controle tiveram melhor desempenho do que ambos os grupos clínicos. Conclusão: Embora tenham sido identificadas diferenças entre indivíduos com TEA e SCHZ, não foi possível determinar padrões ou diferenciar os grupos clínicos.

Translation and cross-cultural adaptation to Brazilian Portuguese of two brief screening tools for youth at risk of psychosis: the Prodromal Questionnaire (PQ-16) and the PRIME-Screen

Abstract Introduction Prodromal characteristics of psychosis have been described for more than a century. Over the last three decades, a variety of studies have proposed methods to prospectively identify individuals (and youth in particular) who are at high risk of developing a psychotic disorder. These studies have validated various screening instruments and made them available in several languages. Here, we describe the translation into Brazilian Portuguese and cross-cultural adaptation of two such screening tools - the Prodromal Questionnaire-16 (PQ-16) and the Prevention through Risk Identification, Management, and Education (PRIME)-Screen. Method Two bilingual native speakers of Brazilian Portuguese translated the questionnaires from English. A native English speaker then performed back-translations into English. These back-translated versions were submitted to the original authors. They provided feedback and later approved the final versions. Results After translation and cross-cultural adaptation, no items needed to be changed in the adapted PQ-16 and four items were revised in the PRIME-Screen. After the peer-review process, we included two suggestions in the PQ-16 to facilitate use of the tool in our cultural and social contexts. The PRIME-Screen did not need further changes. Conclusion These new instruments can help screen Brazilian Portuguese-speaking patients who are at risk of psychosis in primary care.

Identifying Depression Early in Adolescence: assessing the performance of a risk score for future onset of depression in an independent Brazilian sample

Objective: The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) was recently developed in Brazil using data from the Pelotas 1993 Birth Cohort to estimate the individualized probability of developing depression in adolescence. This model includes 11 sociodemographic variables and has been assessed in longitudinal studies from four other countries. We aimed to test the performance of IDEA-RS in an independent, community-based, school-attending sample within the same country: the Brazilian High-Risk Cohort. Methods: Standard external validation, refitted, and case mix-corrected models were used to predict depression among 1442 youth followed from a mean age of 13.5 years at baseline to 17.7 years at follow-up, using probabilities calculated with IDEA-RS coefficients. Results: The area under the curve was 0.65 for standard external validation, 0.70 for the case mix-corrected model, and 0.69 for the refitted model, with discrimination consistently above chance for predicting depression in the new dataset. There was some degree of miscalibration, corrected by model refitting (calibration-in-the-large reduced from 0.77 to 0). Conclusion: IDEA-RS was able to parse individuals with higher or lower probability of developing depression beyond chance in an independent Brazilian sample. Further steps should include model improvements and additional studies in populations with high levels of subclinical symptoms to improve clinical decision making.

Clozapine prescription trends in Brazil in the last decade

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Predictors of gaming disorder in children and adolescents: a school-based study

Objective: To determine whether psychiatric and gaming pattern variables are associated with gaming disorder in a school-based sample. Methods: We analyzed data from the Brazilian High-Risk Cohort for Psychiatric Disorders, a community sample aged 10 to 18, using questionnaires on gaming use patterns. We applied the Gaming Addiction Scale to diagnose gaming disorder and the Development and Well-Being Behavior Assessment for other diagnoses. Results: Out of 407 subjects, 83 (20.4%) fulfilled the criteria for gaming disorder. More role-playing game players were diagnosed with gaming disorder that any other genre. Gaming disorder rates increased proportionally to the number of genres played. Playing online, being diagnosed with a mental disorder, and more hours of non-stop gaming were associated with higher rates of gaming disorder. When all variables (including age and gender) were considered in a logistic regression model, the number of genres played, the number of non-stop hours, the proportion of online games, and having a diagnosed mental disorder emerged as significant predictors of gaming disorder. Conclusion: Each variable seems to add further risk of gaming disorder among children and adolescents. Monitoring the length of gaming sessions, the number and type of genres played, time spent gaming online, and behavior changes may help parents or guardians identify unhealthy patterns of gaming behavior.

The impact of child psychiatric conditions on future educational outcomes among a community cohort in Brazil.

AIMS: Mental health problems early in life can negatively impact educational attainment, which in turn have negative long-term effects on health, social and economic opportunities. Our aims were to: (i) estimate the impacts of different types of psychiatric conditions on educational outcomes and (ii) to estimate the proportion of adverse educational outcomes which can be attributed to psychiatric conditions. METHODS: Participants (N = 2511) were from a school-based community cohort of Brazilian children and adolescents aged 6-14 years enriched for high family risk of psychiatric conditions. We examined the impact of fear- (panic, separation and social anxiety disorder, specific phobia, agoraphobia and anxiety conditions not otherwise specified), distress- (generalised anxiety disorder, major depressive disorder and depressive disorder not otherwise specified, bipolar, obsessive-compulsive, tic, eating and post-traumatic stress disorder) and externalising-related conditions (attention deficit and hyperactivity disorder, conduct and oppositional-defiant conditions) on grade repetition, dropout, age-grade distortion, literacy performance and bullying perpetration, 3 years later. Psychiatric conditions were ascertained by psychiatrists, using the Development and Well-Being Behaviour Assessment. Propensity score and inverse probability weighting were used to adjust for potential confounders, including comorbidity, and sample attrition. We calculated the population attributable risk percentages to estimate the proportion of adverse educational outcomes in the population which could be attributed to psychiatric conditions. Analyses were conducted separately for males and females. RESULTS: Fear and distress conditions in males were associated with school dropout (odds ratio (OR) = 2.76; 95% confidence interval (CI) = 1.06, 7.22; p < 0.05) and grade repetition (OR = 2.76; 95% CI = 1.32, 5.78; p < 0.01), respectively. Externalising conditions were associated with grade repetition in males (OR = 1.66; 95% CI = 1.05, 2.64; p < 0.05) and females (OR = 2.03; 95% CI = 1.15, 3.58; p < 0.05), as well as age-grade distortion in males (OR = 1.66; 95% CI = 1.05, 2.62; p < 0.05) and females (OR = 2.88; 95% CI = 1.61, 5.14; p < 0.001). Externalising conditions were also associated with lower literacy levels (ß = -0.23; 95% CI = -0.34, -0.12; p < 0.001) and bullying perpetration (OR = 3.12; 95% CI = 1.50, 6.51; p < 0.001) in females. If all externalising conditions were prevented or treated, we estimate that 5.0 and 4.8% of grade repetition would not have occurred in females and males, respectively, as well as 10.2 (females) and 5.3% (males) of age-grade distortion cases and 11.4% of female bullying perpetration. CONCLUSIONS: The study provides evidence of the negative impact of psychiatric conditions on educational outcomes in a large Brazilian cohort. Externalising conditions had the broadest and most robust negative impacts on education and these were particularly harmful to females which are likely to limit future socio-economic opportunities.

Lowering costs for large-scale screening in psychosis: a systematic review and meta-analysis of performance and value of information for speech-based psychiatric evaluation

Objective: Obstacles for computational tools in psychiatry include gathering robust evidence and keeping implementation costs reasonable. We report a systematic review of automated speech evaluation for the psychosis spectrum and analyze the value of information for a screening program in a healthcare system with a limited number of psychiatrists (Maputo, Mozambique). Methods: Original studies on speech analysis for forecasting of conversion in individuals at clinical high risk (CHR) for psychosis, diagnosis of manifested psychotic disorder, and first-episode psychosis (FEP) were included in this review. Studies addressing non-verbal components of speech (e.g., pitch, tone) were excluded. Results: Of 168 works identified, 28 original studies were included. Valuable speech features included direct measures (e.g., relative word counting) and mathematical embeddings (e.g.: word-to-vector, graphs). Accuracy estimates reported for schizophrenia diagnosis and CHR conversion ranged from 71 to 100% across studies. Studies used structured interviews, directed tasks, or prompted free speech. Directed-task protocols were faster while seemingly maintaining performance. The expected value of perfect information is USD 9.34 million. Imperfect tests would nevertheless yield high value. Conclusion: Accuracy for screening and diagnosis was high. Larger studies are needed to enhance precision of classificatory estimates. Automated analysis presents itself as a feasible, low-cost method which should be especially useful for regions in which the physician pool is insufficient to meet demand.

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics.

Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.

Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries

Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.

Patients with Schizophrenia Undergoing Gastric Bypass Surgery: a Case Series Study.

PURPOSE: Obesity affects approximately 45-55% of persons with schizophrenia and is more difficult to manage in these individuals than in the general population, apart from being an additional factor for morbidity and premature mortality. Although bariatric surgery is considered the most effective long-term treatment for severe obesity, there are few reports on the outcomes of this procedure in persons with schizophrenia. This study aimed to evaluate weight loss and psychiatric symptoms in persons with obesity and schizophrenia after bariatric surgery. MATERIALS AND METHODS: Five persons with schizophrenia and moderate to severe obesity who underwent bariatric surgery were followed up for 2 years. Anthropometric data were collected, and psychiatric symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), which assessed the pre- and postoperative occurrence and severity of symptoms of schizophrenia. RESULTS: The mean body mass index before surgery was 43.5 ± 5.2 kg/m2 and decreased to 28.1 ± 1.9 kg/m2 1 year postoperatively. The mean percentage of total postoperative weight loss was 30.7 ± 6.8% after 6 months, 34.7 ± 7.9% after 1 year, and 34.3 ± 5.5% after 2 years. Before surgery, all subjects were in remission based on the PANSS. Postoperative evaluations showed that the participants had no relapse of psychiatric symptoms (p > 0.05 for the three PANSS dimensions throughout the follow-up period). There were no considerable changes in their medication regimens. CONCLUSIONS: These findings suggest that bariatric surgery may be a viable treatment option for stable patients with schizophrenia if they have a preoperative assessment and close management and involvement by mental health professionals throughout the course of treatment.

Lowering costs for large-scale screening in psychosis: a systematic review and meta-analysis of performance and value of information for speech-based psychiatric evaluation.

OBJECTIVE: Obstacles for computational tools in psychiatry include gathering robust evidence and keeping implementation costs reasonable. We report a systematic review of automated speech evaluation for the psychosis spectrum and analyze the value of information for a screening program in a healthcare system with a limited number of psychiatrists (Maputo, Mozambique). METHODS: Original studies on speech analysis for forecasting of conversion in individuals at clinical high risk (CHR) for psychosis, diagnosis of manifested psychotic disorder, and first-episode psychosis (FEP) were included in this review. Studies addressing non-verbal components of speech (e.g., pitch, tone) were excluded. RESULTS: Of 168 works identified, 28 original studies were included. Valuable speech features included direct measures (e.g., relative word counting) and mathematical embeddings (e.g.: word-to-vector, graphs). Accuracy estimates reported for schizophrenia diagnosis and CHR conversion ranged from 71 to 100% across studies. Studies used structured interviews, directed tasks, or prompted free speech. Directed-task protocols were faster while seemingly maintaining performance. The expected value of perfect information is USD 9.34 million. Imperfect tests would nevertheless yield high value. CONCLUSION: Accuracy for screening and diagnosis was high. Larger studies are needed to enhance precision of classificatory estimates. Automated analysis presents itself as a feasible, low-cost method which should be especially useful for regions in which the physician pool is insufficient to meet demand.

Schneider's first-rank symptoms as predictors of remission in antipsychotic-naive first-episode psychosis

Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis. Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS. Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting. Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.