Mood disorders in childhood and adolescence

The identification and treatment of mood disorders in children and adolescents has grown over the last decades. Major depression is one of the most common and debilitating disorders worldwide, imposing a massive burden to the youth population. Bipolar disorder is being increasingly recognized as having its roots early in life, and its presentation during childhood and adolescence has been submitted to extensive research. This review aims to highlight clinical aspects of the current knowledge on mood disorders in the pediatric population, presenting updated information on epidemiology, diagnostic procedures, and management strategies. Limitations of available evidence and future directions of research in the field are also discussed.Universidade Federal do Rio Grande do Sul Hospital de Clinicas de Porto Alegre Department of PsychiatryUniversidade Federal de São Paulo (UNIFESP) Department of Psychiatry Child and Adolescent Psychiatry UnitUNIFESP, Department of Psychiatry Child and Adolescent Psychiatry UnitSciEL

CLOCK polymorphisms in attention-deficit/hyperactivity disorder (ADHD) : further evidence linking sleep and circadian disturbances and ADHD

Circadian and sleep disorders, short sleep duration, and evening chronotype are often present in attention-deficit/hyperactivity disorder (ADHD). CLOCK, considered the master gene in the circadian rhythm, has been explored by few studies. Understanding the relationship between ADHD and CLOCK may provide additional information to understand the correlation between ADHD and sleep problems. In this study, we aimed to explore the association between ADHD and CLOCK, using several genetic markers to comprehensively cover the gene extension. A total of 259 ADHD children and their parents from a Brazilian clinical sample were genotyped for eight single nucleotide polymorphisms (SNPs) in the CLOCK locus. We tested the individual markers and the haplotype effects using binary logistic regression. Binary logistic and linear regressions considering ADHD symptoms among ADHD cases were conducted as secondary analysis. As main result, the analysis showed a risk effect of the G-A-T-G-G-C-G-A (rs534654, rs1801260, rs6855837, rs34897046, rs11931061, rs3817444, rs4864548, rs726967) haplotype on ADHD. A suggestive association between ADHD and rs534654 was observed. The results suggest that the genetic susceptibility to circadian rhythm attributed to the CLOCK gene may play an important role on ADHD

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 mm3 , 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

Brian scale adaptation for use in children and adolescents : a preliminary study

Introdução: Alterações nos ritmos circadianos tem sido frequentemente observadas entre pacientes com Transtorno do Humor Bipolar (THB). No entanto, existem poucos instrumentos para medi-las e a maioria deles mede exclusivamente distúrbios do sono. A escala BRIAN, validada para adultos com THB, avalia a regularidade dos ritmos biológicos em quatro diferentes aspectos: sono, atividades, social e padrão de alimentação. O objetivo deste estudo-piloto foi adaptar a escala BRIAN para uma população de crianças e adolescentes (BRIAN-K) e avaliar se o novo instrumento é capaz de detectar diferenças entre pacientes e controles saudáveis. Métodos: Foram avaliados 20 pacientes com THB entre 8-16 anos e 32 controles pareados por sexo e idade. Os sujeitos foram avaliados por meio de entrevista clínica, K-SADS-PL e testagem cognitiva. A BRIAN-K foi aplicada em ambos os grupos. Resultados: O grupo de pacientes com THB apresentou escores mais altos de alterações em seus ritmos circadianos pelo escore total da BRIAN-K, quando comparados com o grupo controle (p=0,022). Particularmente, maior irregularidade foi observada no domínio “atividades” no grupo de pacientes (p=0,001). Nossos resultados também mostraram uma correlação positiva entre a idade de diagnóstico e o domínio “sono” da BRIAN-K (r=0,485; p=0,03). Conclusões: Estes dados preliminares sugerem que a versão BRIAN-K, recentemente adaptada para crianças e adolescentes, é capaz de discriminar pacientes com THB e controles. Futuros estudos com maior tamanho amostral são necessários para determinar a confiabilidade, a validade interna e externa do presente instrumento.Background: Alterations in the circadian rhythms have been frequently observed in patients with Bipolar Disorder (BD). However, there are few instruments to measure these changes, and most of them only assess sleep disorders. The BRIAN scale validated for adults with BD, evaluates the regularity of the biological rhythms in four different aspects: sleep, activities, social rhythm, and eating pattern. The objective of this pilot study was to adapt the BRIAN scale to a sample of children and adolescents (BRIAN-K) and to evaluate if the new instrument is capable of detecting differences among patients and healthy controls.Methods: Twenty patients with BD, aged between 8 and 16 years, and 32 controls matched for gender and age were included. Participants were assessed using the clinical interview Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS-PL) and cognitive testing. The BRIAN-K was administered to both groups. Results: The group of patients with BD had higher scores of alterations in the circadian rhythms according to the BRIAN-K total score when compared to the control group (p=0.022). Particularly, more irregularity was found in the “activities” domain in the group of patients (p=0.001). Our results have also showed a positive correlation between the age at diagnosis and the “sleep” domain of the BRIAN-K (r=0.485; p=0.03). Conclusions: These preliminary data suggest that the BRIAN-K version, recently adapted for children and adolescents, can differentiate patients and controls. Future studies with a larger sample size are necessary to determine the reliability, as well as the internal and external validity of the present instrument

Adaptação da escala Brian para uso em crianças e adolescentes: um estudo preliminar

Introdução: Alterações nos ritmos circadianos tem sido frequentemente observadas entre pacientes com Transtorno do Humor Bipolar (THB). No entanto, existem poucos instrumentos para medi-las e a maioria deles mede exclusivamente distúrbios do sono. A escala BRIAN, validada para adultos com THB, avalia a regularidade dos ritmos biológicos em quatro diferentes aspectos: sono, atividades, social e padrão de alimentação. O objetivo deste estudo piloto foi adaptar a escala BRIAN para uma população de crianças e adolescentes (BRIAN-K) e avaliar se o novo instrumento é capaz de detectar diferenças entre pacientes e controles saudáveis. Métodos: Foram avaliados 20 pacientes com THB entre 8-16 anos e 32 controles pareados por sexo e idade. Os sujeitos foram avaliados através de entrevista clínica, K-SADS-PL e testagem cognitiva. A BRIAN-K foi aplicada em ambos os grupos.Resultados: O grupo de pacientes com THB apresentou escores mais altos de alterações em seus ritmos circadianos pelo escore total da BRIAN-K, quando comparados com o grupo controle (p=0,022). Particularmente, maior irregularidade foi observada no domínio “atividades” no grupo de pacientes (p=0,001). Nossos resultados também mostraram uma correlação positiva entre a idade de diagnóstico e o domínio “sono” da BRIAN-K (r = 0,485; p = 0,03).Conclusões: Estes dados preliminares sugerem que a versão BRIAN-K, recentemente adaptada para crianças e adolescentes, é capaz de discriminar pacientes com THB e controles. Futuros estudos com maior tamanho amostral são necessários para determinar a confiabilidade, validade interna e externa do presente instrumento

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

Associação entre resposta clínica e eventos adversos ao metilfenidato e genes dopaminérgicos e serotoninérgicos em crianças e adolescentes com transtorno de déficit de atenção/hiperatividade

Introdução: Poucos estudos sobre a farmacogenética do Transtorno de Déficit de Atenção/Hiperatividade (TDAH) foram conduzidos até o momento, apesar da extensa literatura sobre a participação de genes na etiologia do TDAH. Os estudos farmacogenéticos podem auxiliar na identificação a priori dos indivíduos que se beneficiarão de determinados tratamentos e dos que possivelmente apresentarão intolerância aos agentes farmacológicos. A maior parte dos estudos, até o momento, avaliou genes do sistema dopaminérgico e resultou em achados tanto positivos quanto negativos. Métodos: em um estudo naturalístico avaliamos os efeitos dos polimorfismos dos genes candidatos dopaminérgicos (DRD4, DAT1) e serotoninérgicos (HTR1B, HTR2A e 5-HTT) na resposta ao tratamento em 111 pacientes para os quais foi prescrito metilfenidato. As medidas de desfecho (Swanson, Nolan, and Pelham scale - versão IV – anexo I, Children Global Assessment Scale – anexo II, Barkley’s Stimulants Side Effects Rating Scale – anexo III) foram aplicadas no momento de avaliação e um mês após a intervenção. Resultados: Participaram do estudo 111 famílias de crianças e adolescentes eurobrasileiros de ambos os sexos que apresentavam TDAH segundo o DSM-IV. Estes pacientes foram consecutivamente triados no Programa de Déficit de Atenção/Hiperatividade do Hospital de Clínicas de Porto Alegre entre janeiro de 2003 e maio de 2004. Não foi detectada associação significativa entre os polimorfismos dos genes dopaminérgicos e serotoninérgicos avaliados e a resposta ao metilfenidato ou presença de eventos adversos. Conclusão: Os achados deste estudo quanto aos genes dopaminérgicos são negativos, concordando com três outros estudos disponíveis na literatura. Este foi o primeiro estudo a avaliar o efeito dos genes serotoninérgicos isolados na resposta ao metilfenidato e na presença de eventos adversos. Não foi encontrada nenhuma associação significativa. Os resultados dos estudos existentes são de difícil comparação devido à grande variabilidade metodológica existente entre os estudos. Assim, ensaios controlados multicêntricos prospectivos com maiores tamanhos amostrais são necessários para desvendar o papel dos genes candidatos na resposta ao tratamento para o TDAH