Exploring clozapine use in severe psychiatric symptoms associated with autism spectrum disorder: A scoping review.

BACKGROUND: Patients with autism spectrum disorder (ASD) may experience severe psychiatric symptoms, often unresponsive to conventional pharmacological therapies, highlighting the need for more effective alternatives. AIMS: This study aims to map and synthesize evidence on the use of clozapine as a therapeutic option for managing severe psychiatric symptomatology co-occurring with ASD. METHODS: We conducted a scoping review on multiple sources following the JBI guidelines. The search strategy was inclusive, targeting both peer-reviewed publications and gray literature presenting empirical data on the use of clozapine therapy for patients with ASD accompanied by comorbid psychiatric symptoms. Two independent evaluators performed the selection of studies, data extraction, and critical appraisal. RESULTS: The review included 46 studies, encompassing 122 ASD individuals who received clozapine therapy. The sources of evidence comprise 31 case reports, 8 case series, 6 retrospective observational studies, and 1 quasi-experimental prospective study. The tables present the findings along with a narrative summary. Clozapine treatment demonstrated benefits in four groups of severe and treatment-resistant psychiatric symptoms in ASD patients: disruptive behaviors, psychotic symptoms, catatonia, and mood symptoms. Although side effects were common, tolerability was generally satisfactory. However, severe adverse events, such as seizures, moderate neutropenia, and myocarditis, underscore the need for intensive clinical monitoring. CONCLUSIONS: While clozapine shows promise as a pharmacological intervention for severe psychopathologies in ASD, more rigorous clinical studies are required to elucidate its efficacy and safety in this population. The limited robustness of the evidence calls for caution, signaling an early research stage into this topic.

Brazilian Portuguese Childhood Autism Spectrum Test: an investigation of the factor structure of autistic traits in school-aged children

Objective: There is limited evidence about the cross-cultural validity of autistic symptoms in school-aged children in Brazil. We used data from a large school survey to evaluate the factor structure of autism symptoms in community-dwelling children and adolescents. Methods: We translated the Childhood Autism Spectrum Test to Brazilian Portuguese and performed factor analyses to investigate the factor structure of parent-reported autistic symptoms in a large sample (n=8,571) of children/adolescents from a school survey in the metropolitan area of São Paulo. Results: Autistic symptoms were best conceptualized under a correlated-factors model with two factors: one predominantly characterized by social-communication symptoms and the other by symptoms of inflexible/restricted language, behaviors, and interests. Conclusions: These findings provide evidence that the structure of autistic symptoms in Brazil is similar to that described in other countries, indicating the cross-cultural validity of autism in Brazil.

Brazilian Portuguese Childhood Autism Spectrum Test: an investigation of the factor structure of autistic traits in school-aged children from Brazil.

OBJECTIVE: There is limited evidence about the cross-cultural validity of autistic symptoms in school-aged children in Brazil. We used data from a large school survey to evaluate the factor structure of autism symptoms in community-dwelling children and adolescents. METHODS: We translated the Childhood Autism Spectrum Test to Brazilian Portuguese and performed factor analyses to investigate the factor structure of parent-reported autistic symptoms in a large sample (n=8,571) of children/adolescents from a school survey in the metropolitan area of São Paulo. RESULTS: Autistic symptoms were best conceptualized under a correlated-factors model with two factors: one predominantly characterized by social-communication symptoms and the other by symptoms of inflexible/restricted language, behaviors, and interests. CONCLUSIONS: These findings provide evidence that the structure of autistic symptoms in Brazil is similar to that described in other countries, indicating the cross-cultural validity of autism in Brazil.

Sexual Health in Child and Adolescent Psychiatry: Multi-Site Implementation Through Synchronized Videoconferencing of an Educational Resource Using Standardized Patients.

Objective: Matters of sexuality and sexual health are common in the practice of child and adolescent psychiatry (CAP), yet clinicians can feel ill-equipped to address them with confidence. To address this gap in training and practice, we developed, implemented, and evaluated an educational module enhanced by videotaped depictions of expert clinicians interacting with professional actors performing as standardized patients (SPs). Methods: We developed an educational resource highlighting common issues of sexual health relevant to CAP practice, including sexual development, psychotropic-related side effects, and sexuality in children with autism. We wrote original scripts, based on which two clinicians interacted with three SPs. Digital recordings were edited to yield 5 clips with a cumulative running time of 20 min. The clips were interspersed during a 90-min session comprising didactic and interactive components. Due to the COVID-19 pandemic, we used synchronous videoconferencing, which allowed content dissemination to several training programs across the country. Results: We recruited 125 learners from 16 CAP training programs through the American Academy of CAP's Alliance for Learning and Innovation (AALI). Routine inquiry into adolescent patients' sexual function was uncommon, reported by only 28% of participants, with "awkward" and "uncomfortable" the most common terms mentioned in reference to the clinical task. The didactic intervention led to measurable improvements after 2 weeks in skills and knowledge (p = 0.004) and in attitudes (p < 0.001). The three items with the greatest improvement were: (a) availability of developmentally tailored resources; (b) comfort in addressing sexual development with underage patients; and (c) with parents or guardians of neuroatypical or developmentally disabled patients (p < 0.001 for each). Conclusions: A sexual health curriculum enriched by video-based examples can lead to measurable improvement in outcomes pertinent to the clinical practice of CAP. These educational materials are available for distribution, use and adaptation by local instructors. Our study also provides proof-of-principle for the use of multisite educational initiatives in CAP through synchronized videoconferencing.

Child and adolescent psychiatry training in Brazil, Argentina, Uruguay and Chile: current panorama and future challenges.

Mental disorders affect approximately 10-15% of children and adolescents worldwide. In South America these numbers are probably higher due to poverty and adverse life events that frequently affect this region. The availability of qualified services and well-trained professionals to care for those children are by far insufficient. The aim of this study was to assess and describe child and adolescent psychiatry (CAP) training in Brazil, Argentina, Uruguay, and Chile, to support the development and strengthen training standards. The coordinators of CAP residency programs in Brazil, Argentina, Uruguay, and Chile were invited to answer an online questionnaire about the characteristics of their training programs. Twelve programs from Brazil, three programs from Chile, two from Argentina, and one from Uruguay completed the questionnaires. In the last three countries, CAP is recognized as an independent specialty, while in Brazil it is considered a subspecialty of psychiatry. None of the countries have a national guideline for CAP residency training. Recently, there has been an increase in the number of professionals interested in pursuing a formal CAP training. This is the first study aiming to evaluate the current scenario of CAP training in South America. The results point to a great potential in the evaluated programs, but also to the need for homogeneous criteria for CAP training and evaluation of residents. A more efficient communication among programs would be an enriching strategy for their development, which may be facilitated by the results of this study.

Use of Mental Health Services by Children With Mental Disorders in Two Major Cities in Brazil.

OBJECTIVE: The study examined lifetime use of mental health services among children diagnosed as having mental disorders in two major cities in Brazil and identified characteristics associated with unmet need. METHODS: The data were collected as part of the High Risk Cohort Study, a community study conducted in Sao Paulo and Porto Alegre, Brazil. During the period from 2010 to 2011, a total of 2,511 children ages 6 to 12 were assessed, and 652 were given a diagnosis of at least one mental disorder. The current study analyzed data for a subsample of 651 children with complete information on use of mental health services. RESULTS: Eighty-one percent of the children with mental disorders had not received mental health treatment in the past. The majority who received treatment were treated with psychotherapy or a combination of psychotherapy and medication. Mixed-race children were significantly more likely to have unmet need for treatment, compared with white children. CONCLUSIONS: The high rate of unmet need among children with mental disorders should be addressed with strategies to improve access to health care.

[Childhood Mental Health Problems in Primary Care]. / Prevalência de problemas de saúde mental na infância na atenção primária.

The present population study aimed at identifying the prevalence of mental health problems (MHP) and describing health services use in a sample of children attending Primary Healthcare Units (PHU) in the city of Sao Paulo. Caregivers of 825 6-11 years old children were assessed. MHP were assessed with the Strength and Difficulties Questionnaire and health services use with an adapted version of the Client Receipt Inventory Children`s version. Prevalence of internalizing and externalizing MHP was 30.7% and 18.3%, respectively. Pediatricians were the most consulted health professional (56.7%) and psychologists the most consulted mental health professional (7.9%). Only 3 children were under medication treatment for MHP. The high prevalence of MHP among children in the primary care setting and the low rate of treatment constitute a public health problem. Training programs for health professionals are relevant to help identify and refer MHP cases.

O presente estudo populacional de corte transversal teve como objetivo verificar a prevalência de problemas de saúde mental (PSM) e descrever o uso de serviços de saúde numa amostra de crianças atendidas em unidades de saúde (UBS) do município de São Paulo. Responsáveis de 825 crianças de 6-11 anos de idade foram entrevistados. PSM das crianças foram avaliados pelo "Strength and Difficulties Questionnaire" e uso de serviços por uma versão adaptada do "Client Service Receipt Inventory Children's version". A prevalência de PSM internalizantes e externalizantes foi de 30,7% e 18,3%, respectivamente. O pediatra foi o profissional de saúde mais consultado (56,7%), o psicólogo foi o profissional da saúde mental mais consultado (7,9%). Apenas 3 crianças estavam em tratamento medicamentoso para PSM. A alta prevalência de PSM em crianças atendidas na AP e o baixo número de atendimentos em serviços configuram um importante problema de saúde pública. Programas de capacitação para profissionais são importantes para aprimorar a identificação e o encaminhamento de casos de PSM.

Prevalência de problemas de saúde mental na infância na atenção primária / Childhood Mental Health Problems in Primary Care

Resumo O presente estudo populacional de corte transversal teve como objetivo verificar a prevalência de problemas de saúde mental (PSM) e descrever o uso de serviços de saúde numa amostra de crianças atendidas em unidades de saúde (UBS) do município de São Paulo. Responsáveis de 825 crianças de 6-11 anos de idade foram entrevistados. PSM das crianças foram avaliados pelo "Strength and Difficulties Questionnaire" e uso de serviços por uma versão adaptada do "Client Service Receipt Inventory Children's version". A prevalência de PSM internalizantes e externalizantes foi de 30,7% e 18,3%, respectivamente. O pediatra foi o profissional de saúde mais consultado (56,7%), o psicólogo foi o profissional da saúde mental mais consultado (7,9%). Apenas 3 crianças estavam em tratamento medicamentoso para PSM. A alta prevalência de PSM em crianças atendidas na AP e o baixo número de atendimentos em serviços configuram um importante problema de saúde pública. Programas de capacitação para profissionais são importantes para aprimorar a identificação e o encaminhamento de casos de PSM.

Abstract The present population study aimed at identifying the prevalence of mental health problems (MHP) and describing health services use in a sample of children attending Primary Healthcare Units (PHU) in the city of Sao Paulo. Caregivers of 825 6-11 years old children were assessed. MHP were assessed with the Strength and Difficulties Questionnaire and health services use with an adapted version of the Client Receipt Inventory Children`s version. Prevalence of internalizing and externalizing MHP was 30.7% and 18.3%, respectively. Pediatricians were the most consulted health professional (56.7%) and psychologists the most consulted mental health professional (7.9%). Only 3 children were under medication treatment for MHP. The high prevalence of MHP among children in the primary care setting and the low rate of treatment constitute a public health problem. Training programs for health professionals are relevant to help identify and refer MHP cases.

The economic impact of subthreshold and clinical childhood mental disorders.

BACKGROUND: Mental disorders are common health problems associated with serious impairment and economic impact. AIMS: To estimate the costs of clinical and subthreshold mental disorders in a sample of Brazilian children. METHOD: The High Risk Cohort Study is a community study conducted in two major Brazilian cities. Subjects were 6-14 years old children being registered at school. From an initial pool of 9937 children, two subgroups were further investigated using a random-selection (n = 958) and high-risk group selection procedure (n = 1554), resulting in a sample of 2512 subjects. Mental disorder assessment was made using the Development and Well-Being Assessment. Costs for each child were estimated from the following components: mental health and social services use, school problems and parental loss of productivity. RESULTS: Child subthreshold and clinical mental disorders showed lifetime mean total cost of $1750.9 and $3141.2, respectively. National lifetime cost estimate was $9.9 billion for subthreshold mental disorders and $11.6 billion for clinical mental disorders (values in US$ purchasing power parity). CONCLUSIONS: This study provides evidence that child mental disorders have a great economic impact on society. There is an urgent need to plan an effective system of care with cost-effective programs of treatment and prevention to reduce economic burden.

An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder.

Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two "in silico" protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

Provision of mental healthcare for children and adolescents: a worldwide view.

PURPOSE OF REVIEW: There has been increased attention towards the burden imposed by mental disorders on children and adolescents. The present overview explores the current state of child and adolescent mental healthcare provision around the globe. RECENT FINDINGS: Current research indicates a concerning gap in the provision of care for the child and adolescent population. The disparities between need, demand and access to youth mental healthcare are likely to be even greater in low and- middle-income countries (LAMIC), where the proportion of children and adolescents in the population is higher. The scarcity of available resources for youth mental healthcare, especially in LAMIC, represents a major obstacle to decreasing the impact of mental disorders across the lifespan. SUMMARY: Our review highlights the discrepancy between demands and availability of mental healthcare for youth populations throughout the world. We describe some of the potential contributors to the current state of youth mental healthcare, such as problematic access to services, implementation deficiencies and inadequacy of policies. Recent innovative strategies to reduce these barriers are also presented.

High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results.

The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random = 958; high risk = 1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high-risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub-sample with "high risk" for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information.

Manic symptoms in youth: dimensions, latent classes, and associations with parental psychopathology.

OBJECTIVE: The purpose of the study was to define the latent structure of parent-reported manic symptoms and their association with functional impairment and familial risk in a community sample of Brazilian children. METHOD: We screened for manic symptoms in a community sample of 2,512 children 6 to 12 years of age. Parents of children with "episodes of going abnormally high" completed a detailed mania section (n = 479; 19.1%). Confirmatory factor analysis (CFA) tested a solution with "Under-Control (UC)" and "Exuberant (EX)" dimensions, investigating the severity (threshold) and factor loading of each symptom. We also used latent class analysis (LCA) to evaluate the latent categorical structure of manic symptoms. Associations of these latent constructs with psychiatric comorbidity, psychosocial impairment, and family history of psychopathology were tested. RESULTS: The 2-dimensional model fit the data well. Only the UC dimension was associated with psychiatric morbidity, psychosocial impairment, and a family history of mania, depression, or suicide attempts. Both UC and EX items discriminated subjects with "episodes of going abnormally high," but EX items lay at the mild end of the severity spectrum, whereas UC items lay at the severe end. The LCA yielded a small group of children with high levels of manic symptoms and a distinct profile of psychiatric comorbidity and impairment ("high-symptom group"). CONCLUSION: In a large, community-based sample, we found a 2-dimensional latent structure for parent-reported manic symptoms in youth, and demonstrated familial associations between the UC dimension and affective disorders. Both UC and EX items are clinically useful, but their contributions vary with symptom severity.

Use of mental health services by children and adolescents six months after the World Trade Center attack.

OBJECTIVE: The authors describe use of mental health services among children and adolescents after the September 11, 2001, attack on the World Trade Center. METHODS: Six months after the attack, sixth- through 12th-graders (N=6,986) who were representative of the student population were asked about their use of mental health services to talk about the attack as well as their exposure to the attack, symptoms of posttraumatic stress and major depressive disorders, and any conversations about the attack with a parent, teacher, or religious leader. RESULTS: Eighteen percent had used mental health services. Using in-school services was associated with conversation with a teacher about the attack. Using services outside school was associated with direct exposure to the attack, previous trauma exposure, probable psychiatric diagnosis, and conversation with a teacher or religious leader about the attack. CONCLUSIONS: Teachers and religious leaders can function as gatekeepers to identify children in need following a disaster.

Developments and challenges in the diagnosis and treatment of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often associated with other psychiatric comorbidities, functional impairments, and poor long-term outcomes. The objective of this selected review is to describe current advances and challenges in the diagnosis and treatment of ADHD. The disorder is associated with neurobiological underpinnings and is highly heterogeneous in various aspects, such as symptom profiles, cognitive impairments, and neurobiological and genetic features. The efficacy and safety of short-term pharmacological treatments across the life cycle is well studied, but further research investigating long-term treatment, impact of treatment in preschoolers, and non-pharmacological interventions is needed. Future research is also needed to better characterize the neurodevelopmental pathways of the disorder, linking clinical and neurobiological information, less investigated populations, and new interventions.

Dimensions of oppositionality in a Brazilian community sample: testing the DSM-5 proposal and etiological links.

OBJECTIVE: Investigating dimensions of oppositional symptoms may help to explain heterogeneity of etiology and outcomes for mental disorders across development and provide further empirical justification for the DSM-5-proposed modifications of oppositional defiant disorder (ODD). However, dimensions of oppositionality have not previously been tested in samples outside Europe or the United States. In this study, we used a large Brazilian community sample to compare the fit of different models for dimensions of oppositional symptoms; to examine the association of psychiatric diagnoses and symptoms with dimensions of oppositionality; and to examine the associations between dimensions of oppositionality and parental history of mental disorders. METHOD: A Brazilian community sample of 2,512 children 6 through 12 years old were investigated in this study. Confirmatory factorial analyses were performed to compare the fit of alternative models, followed by linear and logistic regression analyses of associations with psychiatric diagnosis and parental history of psychopathology. RESULTS: A three-factor model with irritable, headstrong, and hurtful dimensions fitted best. The irritable dimension showed a strong association with emotional disorders in the child (p<.001) and history of depression (p<.01) and suicidality (p<.05) in the mother. The headstrong dimension was uniquely associated with attention-deficit/hyperactivity disorder (ADHD) in the child (p<.001) and with maternal history of ADHD symptoms (p<.05). The hurtful dimension was specifically associated with conduct disorder (p< .05). CONCLUSIONS: Our findings from a large community sample of Brazilian children support a distinction between dimensions of oppositionality consistent with current DSM-5 recommendations and provide further evidence for etiological distinctions between these dimensions.

Developments and challenges in the diagnosis and treatment of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often associated with other psychiatric comorbidities, functional impairments, and poor long-term outcomes. The objective of this selected review is to describe current advances and challenges in the diagnosis and treatment of ADHD. The disorder is associated with neurobiological underpinnings and is highly heterogeneous in various aspects, such as symptom profiles, cognitive impairments, and neurobiological and genetic features. The efficacy and safety of short-term pharmacological treatments across the life cycle is well studied, but further research investigating long-term treatment, impact of treatment in preschoolers, and non-pharmacological interventions is needed. Future research is also needed to better characterize the neurodevelopmental pathways of the disorder, linking clinical and neurobiological information, less investigated populations, and new interventions.

Diffusion of efficacious interventions for children and adolescents with mental health problems.

BACKGROUND: Child and adolescent mental health problems are prevalent and require adequate interventions. Despite several evidence-based interventions for these problems described in the literature, few studies addressed strategies to diffuse efficacious interventions for child mental disorders especially in developing countries. METHODS: An extensive but not systematic review of the literature was performed aiming to identify evidence-based interventions for children and adolescents with mental disorders, professionals to target in disseminating these interventions, and the available strategies to diffuse information. RESULTS: Substantial evidence-based information is available to guide preventive, psychosocial and psychopharmacological interventions. The effectiveness of treatments in real-world settings and the cost-effectiveness of interventions are rarely tested. Professionals at different levels (teachers, school counselors, social workers, general practitioners, pediatricians, child psychologists and psychiatrists) should be targeted in diffusing efficacious interventions for child mental health problems worldwide. Telepsychiatry and the internet seem to be the most promising strategies to diffuse knowledge with lower costs. CONCLUSIONS: Medical and allied professionals must incorporate child and adolescent mental health issues in their under- and postgraduate curricula, and be better prepared to critically evaluate available information. Professionals need to disseminate evidence-based programs to guide parents and teachers in developing countries to deal with child and adolescent difficulties. Countries need to explore internet solutions for dissemination of medical information.