Attention-based classification pattern, a research domain criteria framework, in youths with bipolar disorder and attention-deficit/hyperactivity disorder.

OBJECTIVE: The National Institute of Mental Health has initiated the Research Domain Criteria (RDoC) project. Instead of using disorder categories as the basis for grouping individuals, the RDoC suggests finding relevant dimensions that can cut across traditional disorders. Our aim was to use the RDoC's framework to study patterns of attention deficit based on results of Conners' Continuous Performance Test (CPT II) in youths diagnosed with bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), BD+ADHD and controls. METHOD: Eighteen healthy controls, 23 patients with ADHD, 10 with BD and 33 BD+ADHD aged 12-17 years old were assessed. Pattern recognition was used to partition subjects into clusters based simultaneously on their performance in all CPT II variables. A Fisher's linear discriminant analysis was used to build a classifier. RESULTS: Using cluster analysis, the entire sample set was best clustered into two new groups, A and B, independently of the original diagnoses. ADHD and BD+ADHD were divided almost 50% in each subgroup, and there was an agglomeration of controls and BD in group B. Group A presented a greater impairment with higher means in all CPT II variables and lower Children's Global Assessment Scale. We found a high cross-validated classification accuracy for groups A and B: 95.2%. Variability of response time was the strongest CPT II measure in the discriminative pattern between groups A and B. CONCLUSION: Our classificatory exercise supports the concept behind new approaches, such as the RDoC framework, for child and adolescent psychiatry. Our approach was able to define clinical subgroups that could be used in future pathophysiological and treatment studies.

Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder.

Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm(3), respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

Pediatric bipolar disorder: Executive, linguistic, mnemonic, and cognitive efficiency mapping.

Neuropsychological assessment can enrich our understanding of Pediatric Bipolar Disorder (PB). This study aimed to: (1) analyze the occurrence of neuropsychological frequency of deficits and difficulties in children with PB; (2) verify whether there is a performance difference between PB type I (PB-I) and PB type II (PB-II)/unspecified, and between PB with and without ADHD; and (3) verify the cognitive efficiency differences within the PB group and control groups, and among clinical subgroups. Participants in the study were 16 children diagnosed with PB and 40 children with typical development (6-12 years old). The results indicated a high frequency of deficits/difficulties in verbal fluency, cognitive efficiency in performing basic abilities, inhibitory control, cognitive flexibility, and working memory, with emphasis on verbal and executive losses. There were indications that type PB-I and comorbidity with ADHD negatively impact a child's neuropsychological development. The clinical group showed more cognitive efficiency losses compared with the control group, and greater losses were observed in PB-I and in PB with ADHD. The role of neuropsychological evaluation in multidomain and nonlinear statistical analysis is critical to gaining an understanding of the clinical and cognitive heterogeneity of PB.

Descriptive Study of Transgender Youth Receiving Health Care in the Gender Identity Program in Southern Brazil.

Since 2014, the Gender Identity Program (PROTIG) of Hospital de Clínicas de Porto Alegre (HCPA) has been assisting transgender youth seeking gender-affirmative treatment offered at a public health-care service specializing in gender in southern Brazil. This article aims to analyze sociodemographic and clinical data regarding the diagnoses of gender dysphoria and gender incongruence, psychiatric comorbidities, and clinical aspects of a sample of transgender youths seeking health care in the gender identity program. The research protocol consisted of a survey of the data collected in the global psychological evaluation performed at the health-care service for youths diagnosed with gender incongruence and their caretakers. Participating in this research were 24 transgender youths between 8 and 16 years old with diagnostic overlap of gender dysphoria [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)] and gender incongruence [International Classification of Diseases, 11th Revision (ICD-11)] and 34 of their caregivers. Of the young people, 45.8% were positive for some psychiatric comorbidity throughout their lives, with almost half (45.4%) having two or more psychiatric comorbidities in addition to gender dysphoria. The mental health professionals comprising affirmation care teams face the challenge of adapting the care protocols to the uniqueness of each demand by developing individualized forms to promote healthy development. This can be done by focusing not only on medical and physical interventions for gender affirmation but also on the promotion of mental health and general emotional well-being. Thus, the gender affirmation model, which advocates for global assessment and personalized guidance, proved to be adequate. Nevertheless, access to multidisciplinary health services specializing in gender is essential for promoting the general well-being of the population of transgender youth.

Corrigendum: Descriptive Study of Transgender Youth Receiving Health Care in the Gender Identity Program in Southern Brazil.

[This corrects the article DOI: 10.3389/fpsyt.2021.627661.].

Bullying and psychotic symptoms in youth with bipolar disorder.

BACKGROUND: Childhood trauma is associated with psychosis in adults with bipolar disorder (BD). Although bullying represents a widespread form of childhood trauma, no studies thus far have investigated the association of bullying and psychosis in pediatric bipolar disorder (PBD). We aim to examine the association between psychosis in PBD with bullying victimization. METHODS: We included 64 children and adolescents (age± mean= 12±3.43) outpatients with BD spectrum disorders. Psychiatric diagnoses were assessed with the semi- structured interview Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime (KSADS-PL) version with additional depression and manic symptom items derived from the Washington University in St. Louis Kiddie Schedule for Affective Disorders (WASH-U-KSADS). Bullying, demographic, and clinical variables were assessed during the clinical interview. RESULTS: A lifetime history of psychotic symptoms was associated with bullying (p = 0.002), suicidal behavior (p = 0.006), low socioeconomic status (p = 0.04), and severity of PBD (p = 0.02). Only bullying (OR = 7.3; 95%CI = 2-32) and suicidal behavior (OR = 7.6; 95%CI = 1.5-47.8) remained significant after adjustment for confounders. In a supplementary analysis, we developed a model using supervised machine learning to identify the most relevant variables that differentiated participants with psychotic symptoms, which included bullying, Clinical Global Impression-Severity scale (CGI-S), and suicidal behavior (accuracy = 75%, [p = 0.03]; sensitivity = 77.91%; specificity = 69.05%; area under the curve [AUC] = 0.86). LIMITATIONS: Small sample, cross-sectional design, and generalizability of findings beyond the outpatient clinical sample. CONCLUSIONS: Findings underscore the importance of assessing bullying in PBD participants. Future longitudinal studies with larger samples are needed to replicate our findings and determine causality.

Lower estimated intelligence quotient is associated with suicide attempts in pediatric bipolar disorder.

BACKGROUND: Approximately 20% of individual with pediatric bipolar disorder (PBD) have a lifetime history of suicide attempt. Some cognitive measures were associated with a suicide attempt, but no study has assessed the association of this event with the estimated intelligence quotient (IQ) in PBI. In adult Bipolar Disorder no association between IQ and suicidality was found, with different correlations between cognitive measures. There are studies in general population showing a negative correlation and others did not find any association. In Schizophrenia, IQ had a positive correlation with suicide attempt. So, the correlation between IQ and suicidality still controversial. METHODS: We recruited 63 children and adolescents younger than 18 years of age with PBD based on DSM-IV criteria from an outpatient clinic in Brazil. Manic and depressive symptoms were assessed with the YMRS and CDRS, respectively. Estimated IQ was assessed with the WISC-III. The presence or absense of suicidal attempt, clinical and demographic variables were assessed with the K-SADS-PL-W. RESULTS: Patients who attempted suicide had lower estimated IQ compared to patients who did not attempt suicide (82.72 ±â€¯18.70 vs. 101.0 ±â€¯14.36; p = 0.009). This finding remained after correction for depressive symptoms and family income (OR = 0.94; 95% CI = 0.89 - 0.99; p = 0.029). LIMITATIONS: Small sample, reverse causality could not be discarded, we only used two subscales of the WISC-III to estimate intelligence. CONCLUSION: Estimated IQ and suicide attempts were negative correlated in PBD. Future longitudinal and larger studies may confirm our findings.

Clinical differences between patients with pediatric bipolar disorder with and without a parental history of bipolar disorder.

Pediatric Bipolar Disorder (PBD) is a highly heritable condition responsible for 18% of all pediatric mental health hospitalizations. Despite the heritability of this disorder, few studies have assessed potential differences in the clinical manifestation of PBD among patients with a clear parental history of BD. Additionally, while recent studies suggest that attentional deficits are a potential endophenotypic marker of PBD, it is unclear whether heritability is a relevant contributor to these symptoms. In order to address this gap, the present study assessed 61 youth with PBD (6-17 years old), corresponding to 27 offspring of BD patients, and 31 PBD patients without a parental history of the disorder. All standardized assessments, including the K-SADS-PL-W were performed by trained child and adolescent psychiatrists. We performed a logistic multivariate model using the variables of ADHD, rapid cycling, and lifetime psychosis. Rates of ADHD comorbidity were significantly higher among PBD patients who had a parent with BD. Furthermore, PBD patients who had a parent with BD showed a trend toward significance of earlier symptom onset. PBD offspring did not show increased rates of suicide attempts, rapid cycling, or psychosis. Given these findings, it appears that PBD patients who have a parent with BD may represent a distinct endophenotype of the disorder. Future longitudinal and larger studies are required to confirm our findings.

Use of the House-Tree-Person Projective Drawings and Parental Styles Inventory in the Global Psychological Evaluation of Transgender Youth Who Seek Healthcare at the Gender Identity Program.

The present study explores data collected in the psychological evaluation of transgender youth and their families who seek healthcare at the Gender Identity Program. Great psychosocial changes mark the transition from infancy to adulthood. Transgender youth may have these aspects of their developmental stage potentialized. A study was conducted with 23 transgender youth (mean age = 14 ± 2.38 years) and their caregivers. Eleven of the youngsters were assigned male at birth, while 12 were assigned female. The research protocol consisted of a survey and systematization of the data collected in the initial global psychological evaluation performed at the healthcare facility, including house-tree-person (HTP) projective drawings and the parental styles inventory. The present study aimed to explore the data collected during the psychological evaluation of youngsters diagnosed with gender incongruence, relating the HTP projective drawing technique to parental styles and gender trajectories. The results indicate two key points. One evidenced that parental styles could be either preventive or risk components in maintaining adequate socialization in these young people but not in affecting the level of gender dysphoria. The other was that coherence is introduced in the person's perception of his or her projected self-image and his or her expressed gender as he/she becomes more comfortable in expressing his/her gender identity. Treating youngsters inherently brings ethical issues to clinical practice. Thus, global psychological evaluation tailored to this population is a fundamental resource that the psychology professional can use in consultations with youngsters because this tool brings a global understanding about the natural development cycle, facilitating the formulation of therapeutic conducts and exchanges within interdisciplinary transgender health care teams.

Aripiprazole in juvenile bipolar disorder comorbid with attention-deficit/hyperactivity disorder: an open clinical trial.

INTRODUCTION: Juvenile bipolar disorder (JBD) is a highly impairing chronic mental health condition that affects children and adolescents' overall functioning. Comorbidity with attention-deficit/hyperactivity disorder (ADHD) is extremely prevalent and may determine worse response to treatment. Few investigations have addressed the use of recent atypical antipsychotics in JBD, although several guidelines suggest their use. METHODS: We conducted a 6-week open trial with aripiprazole in 10 children and adolescents with JBD comorbid with ADHD to assess impact on mania and ADHD symptoms, respectively, by means of the Young Mania Rating Scale and the Swanson, Nolan and Pelham Scale, as well as on global functioning (Clinical Global Impressions-Severity), and adverse events. RESULTS: Significant improvement in global functioning scores (F=3.17, P=.01, effect size=0.55), manic symptoms (F=5.63, P<.01; ES=0.93), and ADHD symptoms (t=3.42, P<.01;ES=1.05) were detected. Although an overall positive tolerability was reported, significant weight gain (F=3.07, P=.05) was observed. CONCLUSION: Aripiprazole was effective in improving mania and ADHD symptoms, but neither JBD nor ADHD symptom remission was observed in most of the cases. Randomized placebo-controlled trials for JBD and ADHD are needed.

Topiramate in adolescents with juvenile bipolar disorder presenting weight gain due to atypical antipsychotics or mood stabilizers: an open clinical trial.

BACKGROUND: Many children and adolescents with bipolar disorder (BD) do not adhere to the pharmacological treatment due to weight gain. This investigation aims to describe response, side effects, and weight changes in a sample of youths with BPD while receiving topiramate for 11 weeks during the treatment maintenance phase. METHODS: Ten consecutive outpatients with BPD (11-17 years) using a single mood stabilizer and/or an antipsychotic presenting weight gain over 5% of their baseline weight were enrolled in this 11-week protocol. Their medication was switched to topiramate during the first 4 weeks. The Young Mania Rating Scale (Y-MRS) was the main outcome measure to assess response to the treatment in a weekly basis. Side effects and weight were also assessed weekly. RESULTS: In repeated-measure analysis of variance (ANOVA), we found a significant reduction in both the YMRS scores (F = 10.21; p ,0.01) and in weight (F = 8.04; p ,0.01) during the trial. CONCLUSIONS: These initial findings suggesting antimanic effects for topiramate during the treatment maintenance phase associated with weight reductions indicate the need of randomized clinical trials assessing this clinical relevant issue.

Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression.

Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing psychological suffering that accompanies the incongruence between one's experienced or expressed gender and one's assigned gender. Manifestation of GD can be seen early on during childhood and adolescence. During this period, the development of undesirable sexual characteristics marks an acute suffering of being opposite to the sex of birth. Pubertal suppression with gonadotropin releasing hormone analogs (GnRHa) has been proposed for these individuals as a reversible treatment for postponing the pubertal development and attenuating psychological suffering. Recently, increased interest has been observed on the impact of this treatment on brain maturation, cognition and psychological performance. Objectives: The aim of this clinical report is to review the effects of puberty suppression on the brain white matter (WM) during adolescence. WM Fractional anisotropy, voice and cognitive functions were assessed before and during the treatment. MRI scans were acquired before, and after 22 and 28 months of hormonal suppression. Methods: We performed a longitudinal evaluation of a pubertal transgender girl undergoing hormonal treatment with GnRH analog. Three longitudinal magnetic resonance imaging (MRI) scans were performed for diffusion tensor imaging (DTI), regarding Fractional Anisotropy (FA) for regions of interest analysis. In parallel, voice samples for acoustic analysis as well as executive functioning with the Wechsler Intelligence Scale (WISC-IV) were performed. Results: During the follow-up, white matter fractional anisotropy did not increase, compared to normal male puberty effects on the brain. After 22 months of pubertal suppression, operational memory dropped 9 points and remained stable after 28 months of follow-up. The fundamental frequency of voice varied during the first year; however, it remained in the female range. Conclusion: Brain white matter fractional anisotropy remained unchanged in the GD girl during pubertal suppression with GnRHa for 28 months, which may be related to the reduced serum testosterone levels and/or to the patient's baseline low average cognitive performance.Global performance on the Weschler scale was slightly lower during pubertal suppression compared to baseline, predominantly due to a reduction in operational memory. Either a baseline of low average cognition or the hormonal status could play a role in cognitive performance during pubertal suppression. The voice pattern during the follow-up seemed to reflect testosterone levels under suppression by GnRHa treatment.

Attention-deficit/hyperactivity disorder in a diverse culture: do research and clinical findings support the notion of a cultural construct for the disorder?

There is still some debate in the literature whether Attention-Deficit Disorder/Hyperactivity (ADHD) is best conceptualized as a biological disorder or if it is best understood as a cultural construct. This review aims to contribute to disentangle this issue assessing clinical and research data on ADHD in a complete diverse culture from a developing country. We performed a systematic computerized review of the literature on ADHD in Brazil. All investigations were included if dealing with ADHD prevalence, etiology, symptomatological construct, or treatment. Findings were compared to those from studies in developed countries. The prevalence rates of ADHD (5.8% using DSM-IV criteria, 1.5% using ICD-10), the bi-dimensional factor construct extracted from factor analyses (inattention and hyperactivity/impulsivity), the pattern of ADHD comorbidity in clinical samples, the family genetic data suggesting a 39% family transmission in clinical samples and the role of some potential candidate genes in dopaminergic and noradrenergic systems, as well as data on the efficacy of methylphenidate in the disorder are all very similar to findings from developed countries. Taken together, these findings suggest that ADHD is not a cultural construct, reinforcing the importance of applying similar research methodology in different cultures to make findings comparable.

Juvenile bipolar disorder in Brazil: clinical and treatment findings.

BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.

Weekend holidays during methylphenidate use in ADHD children: a randomized clinical trial.

OBJECTIVE: The aim of this study was to assess whether weekend drug holidays during methylphenidate (MPH) administration would change the efficacy and tolerability to the medication in male children with Attention-Deficit Hyperactivity Disorder (ADHD). METHODS: In a 28-day, double-blind study, children with diagnoses of ADHD were randomized to receive BID MPH for 7 days a week (n = 21) or to receive BID MPH on weekdays and a placebo on weekends (n = 19). Parents completed the Conners' Abbreviated Rating Scale (ABRS) to assess ADHD symptoms and the Barkley's Side Effect Rating Scale (SERS) to assess side effects on weekends. Teachers completed the ABRS on each Monday after weekends. RESULTS: Both groups showed a significant reduction on the ABRS over time as the dose was increased. However, the group difference in the ABRS scores was not statistically significant, either on weekend parent ratings (at the endpoint, p = 0.41; effect size = 0.26) or on teachers' ratings (at the endpoint, p = 0.99; effect size = 0.002). The omission of MPH on weekends was associated with significantly less severity of insomnia (F = 3.96, d.f. = 1, p = 0.05) and a trend for less interference on appetite (F = 3.18, d. f. = 1, p = 0.08). CONCLUSION: Our findings suggest that weekend holidays during MPH administration reduce the side effects of insomnia and appetite suppression without a significant increase in symptoms, either on weekends or in the first school day after them. Possible explanations for these findings (rate-dependent response or impact of demands of the environment) are discussed in this paper.

Does comorbid bipolar disorder increase neuropsychological impairment in children and adolescents with ADHD?

OBJECTIVE: To assess differences in executive functioning between children and adolescents with attention-deficit/hyperactivity disorder (ADHD) comorbid or not with bipolar disorder (BD), and to study the neuropsychological profile of subjects with the comorbidity in a clinical sample from a developing country. METHOD: Case-control study comparing 23 participants with BD + ADHD and 85 ADHD-only subjects aged 6 to 17 years old. Both groups were drug-free. Executive function domains were assessed with the Stroop Test, the Wisconsin Card Sorting Test, and the Continuous Performance Test II. RESULTS: The group with juvenile BD + ADHD showed a significantly worse performance on the Stroop task, including time in color (p = 0.002), time in color-word (p < 0.001), interference, number or errors in color and color-word (p = 0.001), and number of errors in word cards (p = 0.028). No between-group differences were found in other tests. CONCLUSIONS: Our findings suggest that ADHD-only and ADHD + BD do not show differences in inhibitory control and set-shifting domains. However, children and adolescents with BD and comorbid ADHD show greater impairment in processing speed and interference control. This suggests a potentially higher impairment in the dorsolateral prefrontal cortex and may be a potential neuropsychological signature of juvenile BD comorbid with ADHD.

Pharmacotherapy of bipolar disorder in children and adolescents: an update.

OBJECTIVE: To review the options for acute and maintenance pharmacological treatment of bipolar disorder in children and adolescents, including the treatment of bipolar depression and comorbid attention deficit/hyperactivity disorder (ADHD). METHODS: Narrative review of randomized clinical trials and open-label studies published from 2000 to 2012. The PubMed and PsycINFO websites were queried. Case series were included when a higher level of evidence was not available. RESULTS: Published data from randomized controlled trials (RCTs) in acute mania/hypomania with significant responses are available for lithium, topiramate, risperidone, olanzapine, and aripiprazole. Open trials of lithium and lamotrigine show that these drugs may be effective in the treatment of depressive episodes. No trials of selective serotonin reuptake inhibitors (SSRIs) have been conducted. In the treatment of comorbid ADHD, there are encouraging findings with mixed amphetamine salts and atomoxetine; conflicting results are observed with methylphenidate. CONCLUSIONS: Published RCTs of traditional mood stabilizers are scarce, but the best available evidence (results from meta-analytic regression) suggests that second-generation antipsychotics (SGAs) as a group are more effective in reducing manic symptoms. Risperidone was the only one included in head-to-head comparisons (vs. lithium and divalproex), showing superiority in terms of efficacy, but with more metabolic side effects, which were also more common in most of the SGAs. There are few studies addressing the treatment of ADHD and depression. Brazilian guidelines for the treatment of pediatric bipolar disorder should also include some SGAs (especially risperidone and aripiprazole) as first-line treatment, and these drugs should be provided by the public health services.

The Val66Met polymorphism at the BDNF gene does not influence Wisconsin Card Sorting Test results in children and adolescents with bipolar disorder.

OBJECTIVES: To assess the role of the Val66Met polymorphism at the brain-derived neurotrophic factor (BDNF) gene on the performance of children and adolescents with bipolar disorder [juvenile bipolar disorder (JBD)] on the Wisconsin Card Sorting Test (WCST). METHODS: Children and adolescents were assessed by the K-SADS-PL and a clinical evaluation for BD and comorbid conditions. Manic and depressive symptoms were assessed with the Young Mania Rating Scale and the Children Depression Rating Scale - Reviewed. The Val66Met polymorphism at the BDNF was genotyped from a blood sample. Patients' IQ and executive functions were assessed by a standard cognitive flexibility test (WCST). RESULTS: Fifty-three subjects were included in the study. No significant difference was observed between the Val/Val and Val/Met+Met/Met groups on any WCST scores in the MANCOVA (F48,5 = .76; p = .59; Perseverative Errors, p = .66; Nonperseverative Errors, p = .58; Categories Completed, p = .34; Attempts to Reach First Category, p=.64; and Percentage of Conceptual Level Responses, p = .99). CONCLUSIONS: Our findings from this sample of children and adolescents with BD do not replicate results from studies of adults and suggest the existence of differences in the neurobiology of this disorder across the life cycle. Investigations of larger samples are necessary to confirm these data.

An open-label trial of risperidone in children and adolescents with severe mood dysregulation.

OBJECTIVE: The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD), has been the focus of increasing concern and debate among clinicians and researchers. Our main objective was to assess the effectiveness of risperidone for youths with SMD. METHODS: An 8-week open label trial with risperidone was conducted. We extensively assessed 97 subjects with semistructured and clinical interviews and enrolled 21 patients in the study. Risperidone was titrated from 0.5 to 3 mg/day in the first 2 weeks. Evaluations were performed at baseline and weeks 2, 4, 6, and 8. Clinical outcome measures were (1) Aberrant Behavior Checklist-Irritability Subscale, (2) Clinical Global Impressions, and (3) severity of co-morbid conditions. RESULTS: We found a significant reduction of the Aberrant Behavior Checklist-Irritability scores during the trial after risperidone use (p < 0.001). The scores at week 2 (mean = 12.03; standard error [SE] = 2.94), week 4 (mean = 15.48; SE = 2.93), week 6 (mean = 12.29; SE = 2.86), and week 8 (mean = 11.28; SE = 3.06) were significantly reduced compared with the baseline mean score (mean = 25.89; SE = 2.76) (p < 0.001). We also found an improvement in attention-deficit/hyperactivity disorder, depression, and global functioning (p < 0.001). CONCLUSION: Risperidone was effective in reducing irritability in SMD youth. To the best of our knowledge, this is the first psychopharmacological trial in this group of patients with positive results. Further randomized, controlled studies are needed.