Efficacy of stimulants for preschool attention-deficit/hyperactivity disorder: A systematic review and meta-analysis.

Background: Robust synthesis of evidence to support treatment recommendations for preschoolers with attention-deficit/hyperactivity disorder (ADHD) is lacking. The aim of this systematic review and meta-analysis was to review currently available evidence to evaluate the efficacy and acceptability of stimulants for preschool children with ADHD. Methods: We searched electronic databases (CENTRAL, Embase, PubMed) from the database inception to March, 2022; and clinical trial registries through WHO ICTRP from the database inception to July, 2022, and selected double-blinded randomized controlled trials (RCTs) that compared stimulants against placebo for the treatment of preschoolers (age ≤ 7 years) with ADHD. Change in ADHD symptom severity was the primary outcome (efficacy) and all-cause dropout rates (acceptability) was the secondary outcome. Data were pooled with random-effects models weighted by the inverse of the variance. Risk of bias of individual studies were assessed with the Cochrane Risk of Bias tool version 2. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence. This study is registered with PROSPERO (CRD42022348597). Results: Five RCTs (three methylphenidate immediate-release, one methylphenidate extended-release, and one lisdexamfetamine) were included. The analysis of efficacy was based on 489 participants. Meta-analysis of change in ADHD symptom severity demonstrated a significant effect in favor of stimulants over placebo (standardized mean difference = -0.59; 95% CI -0.77, -0.41; p < 0.0001). There was no evidence of heterogeneity but some concerns about publication bias. Regardless, the confidence of evidence was considered moderate. For acceptability, stimulants did not lead to an increased rate of all-cause discontinuation rates in comparison to placebo (OR = 0.59; 95% CI 0.15, 2.37; p = 0.45) but the confidence of estimate was very low. Conclusions: Our findings demonstrated that stimulants are efficacious in reducing ADHD symptoms among preschool children. Clinicians should consider the use of stimulants when making treatment recommendations for preschoolers with ADHD.

Children and adolescents' emotional problems during the COVID-19 pandemic in Brazil.

Brazil has been severely affected by the COVID-19 pandemic with one of the largest numbers of youth impacted by school closure globally. This longitudinal online survey assessed emotional problems in children and adolescents aged 5-17 years living in Brazil during the COVID-19 pandemic. Recruitment occurred between June to November 2020 and participants were invited for follow-up assessments every 15 days until June 2021. Participants were 5795 children and adolescents living across the country with mean age of 10.7 (SD 3.63) years at recruitment; 50.5% were boys and 69% of white ethnicity. Weighted prevalence rates of anxiety, depressive and total emotional symptoms at baseline were 29.7%, 36.1% and 36%, respectively. Longitudinal analysis included 3221 (55.6%) participants and revealed fluctuations in anxiety and depressive symptoms during one year follow-up, associated with periods of social mobility and mortality. Emotional problems significantly increased in July and September 2020 and decreased from December 2020 to February 2021 and then significantly increased in May 2021 relative to June 2020. Older age, feeling lonely, previous diagnosis of mental or neurodevelopmental disorder, previous exposure to traumatic events or psychological aggression, parental psychopathology, and sleeping less than 8/h a day were associated with increased rates of anxiety and depressive symptoms at baseline and over time. Food insecurity and less social contact with family and peers were associated with baseline anxiety and depressive symptoms, and lowest socio-economic strata, chronic disease requiring treatment and family members physically ill due to COVID-19 were associated with increasing rates over time. The pandemic severely affected youth, particularly those from vulnerable populations and in moments of increased mortality and decreased social mobility. Results underscore the need for allocation of resources to services and the continuous monitoring of mental health problems among children and adolescents.

Brief internet-delivered cognitive-behavioural intervention for children and adolescents with symptoms of anxiety and depression during the COVID-19 pandemic: a randomised controlled trial protocol.

BACKGROUND: The COVID-19 pandemic has had major impacts in many different spheres, including mental health. Children and adolescents are especially vulnerable because their central nervous system is still in development and they have fewer coping resources than do adults. Increases in the prevalence of depressive and anxiety symptomatology have been reported worldwide. However, access to mental health care is limited, especially for the paediatric population and in low- and middle-income countries. Therefore, we developed a brief internet-delivered cognitive-behavioural intervention for children and adolescents with symptoms of anxiety and depression. The aim of this proposed study is to test the efficacy of the intervention. METHODS: We will conduct a two-arm, parallel randomised controlled trial involving children and adolescents (8-11 and 12-17 years of age, respectively) with symptoms of anxiety, depression or both, according to the 25-item Revised Child Anxiety and Depression Scale (t-score > 70). A total of 280 participants will be randomised to the intervention group or the active control group, in a 1:1 ratio. Those in the intervention group will receive five weekly sessions of cognitive-behavioural therapy via teleconference. The sessions will focus on stress responses, family communication, diaphragmatic breathing, emotions, anger management, behavioural activation and cognitive restructuring. Participants in both groups will have access to 15 videos covering the same topics. Participant-guardian pairs will be expected to attend the sessions (intervention group), watch the videos (control group) or both (intervention group only). A blinded assessor will collect data on symptoms of anxiety, depression and irritability, at baseline, at the end of the intervention and 30 days thereafter. Adolescents with access to a smartphone will also be invited to participate in an ecological momentary assessment of emotional problems in the week before and the week after the intervention, as well as in passive data collection from existing smartphone sensors throughout the study. DISCUSSION: Internet-delivered interventions play a major role in increasing access to mental health care. A brief, manualised, internet-delivered intervention might help children and adolescents with anxiety or depressive symptomatology, even outside the context of the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05139433. Registered prospectively in November 2021. Minor amendments made in July 2022.

Efficacy and safety of methylphenidate and behavioural parent training for children aged 3-5 years with attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled, and sham behavioural parent training-controlled trial.

BACKGROUND: There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. METHODS: We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. FINDINGS: Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. INTERPRETATION: Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. FUNDING: São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.

Validation of an irritability measure in preschoolers in school-based and clinical Brazilian samples.

The Affective Reactivity Index (ARI) is an irritability measure with good psychometric properties. However, there are no published studies in preschool children, an important population in which to differentiate normative from non-normative irritability. The goal of this study was to validate the ARI in preschoolers. Two samples were included: a school-based sample (N = 487, mean age = 57.80 ± 7.23 months, 52.8% male) and a clinical sample of children with Attention Deficit Hyperactivity Disorder (ADHD; N = 153, mean age = 60.5 ± 7.6 months, 83.7% males). Confirmatory factor analysis assessed ARI unidimensionality. ARI criterion validity was tested through comparison to other scales measuring irritability, related constructs, and other aspects of psychopathology. Test-retest reliability was assessed in the school-based sample. Analyses confirmed a single-factor structure and good internal consistency. The ARI showed stronger correlations with irritability measures than with measures of other constructs. In the clinical sample, ADHD children with comorbid disruptive behavior disorders had higher ARI scores than those without this comorbidity. In the school-based sample, test-retest reliability was moderate. This is the first study to demonstrate ARI validity and reliability in preschoolers. The scale performed well in both school-based and clinical samples. Having a concise and validated irritability measure for preschoolers may facilitate both clinical assessment and research on early irritability.

Psychiatric disorders and mental health treatment in American Indians and Alaska Natives: results of the National Epidemiologic Survey on Alcohol and Related Conditions.

PURPOSE: To examine the prevalence of common psychiatric disorders and associated treatment-seeking, stratified by gender, among American Indians/Alaska Natives and non-Hispanic whites in the United States. Lifetime and 12-month rates are estimated, both unadjusted and adjusted for sociodemographic correlates. METHOD: Analyses were conducted with the American Indians/Alaska Native (n = 701) and Non-Hispanic white (n = 24,507) samples in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions [(NESARC) n = 43,093]. RESULTS: Overall, 70 % of the American Indian/Alaska Native men and 63 % of the women met criteria for at least one Diagnostic and Statistical Manual-IV lifetime disorder, compared to 62 and 53 % of Non-Hispanic white men and women, respectively. Adjusting for sociodemographic correlates attenuated the differences found. Nearly half of American Indians/Alaska Natives had a psychiatric disorder in the previous year; again, sociodemographic adjustments explained some of the differences found. Overall, the comparisons to non-Hispanic whites showed differences were more common among American Indian/Alaska Native women than men. Among those with a disorder, American Indian/Alaska Native women had greater odds of treatment-seeking for 12-month anxiety disorders. CONCLUSION: As the first study to provide national estimates, by gender, of the prevalence and treatment of a broad range of psychiatric disorders among American Indians/Alaska Natives, a pattern of higher prevalence of psychiatric disorder was found relative to Non-Hispanic whites. Such differences were more common among women than men. Prevalence may be overestimated due to cultural limitations in measurement. Unmeasured risk factors, some specific to American Indians/Alaska Natives, may also partially explain these results.

Annual research review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents.

BACKGROUND: The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta-analysis to calculate a worldwide-pooled prevalence and to empirically assess the sources of heterogeneity of estimates. METHODS: We conducted a systematic review of the literature searching in PubMed, PsycINFO, and EMBASE for prevalence studies of mental disorders investigating probabilistic community samples of children and adolescents with standardized assessments methods that derive diagnoses according to the DSM or ICD. Meta-analytical techniques were used to estimate the prevalence rates of any mental disorder and individual diagnostic groups. A meta-regression analysis was performed to estimate the effect of population and sample characteristics, study methods, assessment procedures, and case definition in determining the heterogeneity of estimates. RESULTS: We included 41 studies conducted in 27 countries from every world region. The worldwide-pooled prevalence of mental disorders was 13.4% (CI 95% 11.3-15.9). The worldwide prevalence of any anxiety disorder was 6.5% (CI 95% 4.7-9.1), any depressive disorder was 2.6% (CI 95% 1.7-3.9), attention-deficit hyperactivity disorder was 3.4% (CI 95% 2.6-4.5), and any disruptive disorder was 5.7% (CI 95% 4.0-8.1). Significant heterogeneity was detected for all pooled estimates. The multivariate metaregression analyses indicated that sample representativeness, sample frame, and diagnostic interview were significant moderators of prevalence estimates. Estimates did not vary as a function of geographic location of studies and year of data collection. The multivariate model explained 88.89% of prevalence heterogeneity, but residual heterogeneity was still significant. Additional meta-analysis detected significant pooled difference in prevalence rates according to requirement of funcional impairment for the diagnosis of mental disorders. CONCLUSIONS: Our findings suggest that mental disorders affect a significant number of children and adolescents worldwide. The pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world.

Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease.

BACKGROUND: UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function. METHODS: The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model. RESULTS: There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients. CONCLUSIONS: These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.

Child physical abuse and adult mental health: a national study.

This study characterizes adults who report being physically abused during childhood, and examines associations of reported type and frequency of abuse with adult mental health. Data were derived from the 2000-2001 and 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the U.S. population. Weighted means, frequencies, and odds ratios of sociodemographic correlates and prevalence of psychiatric disorders were computed. Logistic regression models were used to examine the strength of associations between child physical abuse and adult psychiatric disorders adjusted for sociodemographic characteristics, other childhood adversities, and comorbid psychiatric disorders. Child physical abuse was reported by 8% of the sample and was frequently accompanied by other childhood adversities. Child physical abuse was associated with significantly increased adjusted odds ratios (AORs) of a broad range of DSM-IV psychiatric disorders (AOR = 1.16-2.28), especially attention-deficit hyperactivity disorder, posttraumatic stress disorder, and bipolar disorder. A dose-response relationship was observed between frequency of abuse and several adult psychiatric disorder groups; higher frequencies of assault were significantly associated with increasing adjusted odds. The long-lasting deleterious effects of child physical abuse underscore the urgency of developing public health policies aimed at early recognition and prevention.

Differences among major depressive disorder with and without co-occurring substance use disorders and substance-induced depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: To investigate the association between substance use disorders (SUDs) and the clinical presentation, risk factors, and correlates of major depressive disorder (MDD) by examining differences among 3 groups: (1) individuals with lifetime MDD and no comorbid SUD (MDD-NSUD); (2) individuals with comorbid MDD and SUD (MDD-SUD); and (3) individuals with substance-induced depressive disorder (SIDD). METHOD: Data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. RESULTS: The lifetime prevalence of MDD-NSUD was 7.41%, whereas those of MDD-SUD and SIDD were 5.82% and 0.26%, respectively. Overall, risk factors for MDD were more common among individuals with MDD-SUD and SIDD than among those with MDD-NSUD. Individuals with MDD-SUD and SIDD had similar rates of comorbidity with any psychiatric disorder, but both groups had higher rates than individuals with MDD-NSUD (odds ratio [OR] = 2.3; 95% CI, 1.9-2.7 and OR = 2.5; 95% CI, 1.4-4.4, respectively). Individuals with SIDD were significantly less likely to receive medication than those with MDD-SUD or MDD-NSUD (OR = 0.5; 95% CI, 0.3-0.9 for both groups). CONCLUSIONS: MDD-SUD is associated with high overall vulnerability to additional psychopathology, a higher number of and more severe depressive episodes, and higher rates of suicide attempts in comparison to individuals with MDD-NSUD. SIDD has low prevalence in the general population but is associated with increased clinical severity and low rates of medication treatment. Similar patterns of comorbidity and risk factors in individuals with SIDD and those with MDD-SUD suggest that the 2 conditions may share underlying etiologic factors.