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.

A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort.

BACKGROUND: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. RESULTS: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. CONCLUSIONS: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.

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.

Serum immune markers and transition to psychosis in individuals at clinical high risk.

Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood-brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines.

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.

Neuroimaging of Dopamine Transporter Density in the Striatum of Disordered Gamblers.

The aim of the present research was to add to the growing literature on dopamine and gambling disorder (GD) by assessing whether GD is associated with dopamine transporter (DAT) density in the ventral striatum compared to healthy controls and whether DAT density was associated with key characteristics of GD (e.g., abstinence, craving). In a cross-sectional investigation using single-photon emission computed tomography with a technetium-99m-labeled tropane derivative as a radiotracer with SPECT imaging, fifteen participants with GD and 15 controls (non-gambling individuals, matched for age, gender, handedness, and smoking status) were measured. The GD group completed self-reported questionnaires regarding gambling. Striatal DAT density did not differ between the two groups. Conversely, striatal DAT density correlated significantly with various measures of recent gambling, but not with measures of chronic gambling. Multivariate analysis, adjusted for age and smoking status, showed that DAT density in the left striatum correlated positively with time spent gambling and gambling craving in the last month, whereas DAT density in the right striatum correlated negatively with abstinence self-efficacy. The results suggests that DAT density in the striatum is associated with recent gambling activity and gambling expectation.

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.

Unraveiling the correlation among neurodevelopmental and inflammatory biomarkers in patients with chronic schizophrenia.

INTRODUCTION: Nuclear distribution element like-1 (Ndel1) is a cytosolic oligopeptidase, which was suggested as a potential biomarker of aberrant neurodevelopment and early stage of schizophrenia (SCZ). The involvement of Ndel1 in neurite outgrowth, neuronal migration and neurodevelopment was demonstrated. Moreover, Ndel1 cleaves neuropeptides, including the endogenous antipsychotic peptide neurotensin, and lower Ndel1 activity was reported in SCZ patients compared with healthy controls (HCs). Changes in brain-derived neurotrophic factor (BDNF) and inflammatory cytokines levels were also implicated in SCZ. OBJECTIVE: This preliminary study aimed to investigate the interactions between these immune and neurodevelopmental/neurotrophic biomarkers, namely BDNF and the recently identified SCZ biomarker Ndel1. RESULTS: We observed lower Ndel1 activity and IL-4 levels, and higher BDNF levels, in plasma of SCZ (N = 23) compared with HCs (N = 29). Interestingly, significant correlation between Ndel1 activity and IL-4 levels was observed in SCZ, while no correlation with any other evaluated interleukins (namely IL-2, IL-8, IL-10 and IL-17A) or BDNF levels was noticed. CONCLUSION: Although this hypothesis needs to be further explored for a better understanding of the mechanisms by which these altered pathways are associated to each other in SCZ, we suggest that Ndel1 and the inflammatory marker IL-4 are directly correlated.

Adolescent depression and resting-state fMRI brain networks: a scoping review of longitudinal studies

The neurobiological factors associated with the emergence of major depressive disorder (MDD) in adolescence are still unclear. Previous cross-sectional studies have documented aberrant connectivity in resting-state functional magnetic resonance imaging (rs-fMRI) networks. However, whether these findings precede MDD onset has not been established. This scoping review mapped key methodological aspects and main findings of longitudinal rs-fMRI studies of MDD in adolescence. Three sets of neuroimaging methods to analyze rs-fMRI data were identified: seed-based analysis, independent component analysis, and network-based approaches. Main findings involved aberrant connectivity within and between the default mode network (DMN), the cognitive control network (CCN), and the salience network (SN). Accordingly, we utilized Menon's (2011) triple-network model for neuropsychiatric disorders to summarize key results. Adolescent MDD was associated with hyperconnectivity within the SN and between DMN and SN, as well as hypoconnectivity within the CCN. These findings suggested that dysfunctional connectivity among the three main large-scale brain networks preceded MDD onset. However, there was high heterogeneity in neuroimaging methods and sampling procedures, which may limit comparisons between studies. Future studies should consider some level of harmonization for clinical instruments and neuroimaging methods.

Cannabidiol for the treatment of crack-cocaine craving: an exploratory double-blind study

Objective: To assess the efficacy of cannabidiol (CBD) in the management of crack-cocaine craving and the treatment of frequent withdrawal symptoms. Methods: Thirty-one men with a diagnosis of crack-cocaine dependence were enrolled in a randomized, double-blind, placebo-controlled trial. We applied neuropsychological tests and assessed craving intensity, anxiety and depression symptoms, and substance use patterns at baseline and at the end of the trial. The participants were treated with CBD 300 mg/day or placebo for 10 days. During this period, we used a technique to induce craving and assessed the intensity of symptoms before and after the induction procedure. Results: Craving levels reduced significantly over the 10 days of the trial, although no differences were found between the CBD and placebo groups. Craving induction was successful in both groups, with no significant differences between them. Indicators of anxiety, depression, and sleep alterations before and after treatment also did not differ across groups. Conclusion: Under the conditions of this trial, CBD was unable to interfere with symptoms of crack-cocaine withdrawal. Further studies with larger outpatient samples involving different doses and treatment periods would be desirable and timely to elucidate the potential of CBD to induce reductions in crack-cocaine self-administration.

Association between tobacco use and symptomatology in individuals at ultra-high risk to develop a psychosis: A longitudinal study.

BACKGROUND: The high prevalence rates and impact of tobacco smoking in individuals with a psychotic disorder have become an increasing interest. Little is known about tobacco smoking in individuals at ultra-high risk of psychosis (UHR). METHODS: We studied 345 UHR individuals of the high-risk study of the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI). Smoking status and the number of cigarettes per day were assessed at multiple moments using the CIDI. Symptom severity at each time point was assessed using CAARMS. Linear mixed-effects analyses were conducted to examine the multi-cross-sectional and prospective associations between (change in) smoking behaviour and symptomatology. FINDINGS: At baseline, 175 individuals (53%) smoked tobacco with an average of 12.4 (SD = 9.0) cigarettes per day. Smokers did not significantly differ in symptom severity from non-smokers on general, positive, negative, emotional, cognitive, behavioural, or motor symptoms across time. However, associations were found between the number of cigarettes and the severity of general psychopathology (estimate 0.349, SE 0.146, p = 0.017). Change in the number of cigarettes had no significant effect on change in general symptom severity (estimate 0.330, SE 0.285, p = 0.248). INTERPRETATION: Smoking prevalence in UHR individuals is high. Cigarette consumption was associated with higher levels of general symptoms. However, we observed no association between change in number of cigarettes and symptom severity. Given the fact that smoking is associated with poorer health and worse outcomes in people with psychosis, the clinical high-risk phase offers a window of opportunity for prevention and cessation interventions.

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.

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.

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.