Refining patterns of MEF2C effects in white matter microstructure and psychiatric features.

Several GWAS reported Myocyte Enhancer Factor 2 C (MEF2C) gene associations with white matter microstructure and psychiatric disorders, and MEF2C involvement in pathways related to neuronal development suggests a common biological factor underlying these phenotypes. We aim to refine the MEF2C effects in the brain relying on an integrated analysis of white matter and psychiatric phenotypes in an extensively characterized sample. This study included 870 Brazilian adults (47% from an attention-deficit/hyperactivity disorder outpatient clinic) assessed through standardized psychiatric interviews, 139 of which underwent a magnetic resonance imaging scan. We evaluated variants in the MEF2C region using two approaches: 1) a gene-wide analysis, which uses the sum of polymorphism effects, and 2) SNP analyses, restricted to the independent variants within the gene. The outcomes included psychiatric phenotypes and fractional anisotropy for brain images. Results: The gene-wide analyses pointed to a nominal association between MEF2C and the Temporal Portion of the Superior Longitudinal Fasciculus (SLFTEMP). The SNP analysis identified four independent variants significantly associated with SLFTEMP and one (rs4218438) with Substance Use Disorder. Our findings showing specific associations of MEF2C variants with temporal-frontal circuitry components may help to elucidate how the MEF2C gene underlies a broad range of psychiatric phenotypes since these regions are relevant to executive and cognitive functions.

The course of attention-deficit/hyperactivity disorder through midlife.

The course of ADHD from childhood up to young adulthood has been characterized in several studies. However, little is known about the course of symptoms into middle age and beyond. This study aims to evaluate predictors of ADHD trajectories in midlife based on three assessments. The follow-up sample comprised 323 adults with ADHD, evaluated at baseline and seven and thirteen years later, from the average ages of 34 up to 47 years old. ADHD status at reassessments was used to characterize trajectories. Demographics, ADHD features, comorbidities, and polygenic scores for ADHD and genetically correlated psychiatric disorders were evaluated to predict ADHD trajectories. Study retention rate was 67% at T2 (n = 216) and 62% at T3 (n = 199). Data from patients evaluated three times showed that 68.8% coursed stable, 25.5% unstable, and 5.7% remission trajectory of ADHD. Women, individuals with more severe syndromes, higher frequency of comorbidities at reassessments, and genetic liability to depression present a higher probability of a stable trajectory. Our findings shed light on midlife ADHD trajectories and their gender, genomic and clinical correlates.

Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

OBJECTIVES: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. METHODS: Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. RESULTS: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). CONCLUSION: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings.

The role of a mineralocorticoid receptor gene functional polymorphism in the symptom dimensions of persistent ADHD.

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5 % of school-aged children and 2.5 % of adults. Genetic studies in ADHD have pointed to genes in different neurobiological systems, with relatively small individual effects. The mineralocorticoid receptor is the main receptor involved in the initial triggering of stress response. Therefore, its encoding gene (NR3C2) is a candidate for psychiatric disorder studies, including ADHD, and behavioral phenotypes. There is evidence that the Val allele of the MRI180V polymorphism (rs5522) increases the risk of depression, attention and cognitive deficits. We investigated the possible role of the mineralocorticoid receptor gene in the symptom dimensions and susceptibility to persistent ADHD. We compared genotype and allele frequencies in 478 adult patients with ADHD and 597 controls and symptom dimensions in 449 patients and 132 controls. Diagnoses were based on the DSM-IV criteria. ADHD symptom dimensions were investigated with SNAP-IV for ADHD severity and Barkley scales for severity and impairment. Carriers of the Val allele presented higher inattention, hyperactivity/impulsivity and impairment scores, while genotype and allele frequencies did not differ between patients and controls. These results are consistent with a possible link between genetic variations in the HPA axis and inattention and hyperactivity measures.

ADRA2A polymorphisms and ADHD in adults: possible mediating effect of personality.

Several studies have tested for the association between polymorphisms in the ADRA2A gene and childhood ADHD. A meta-analysis of these results, however, has pointed towards a significant heterogeneity, raising the need for explanatory studies. As the effect of other relevant clinical characteristics could be a possible source, we studied three polymorphisms in the ADRA2A gene (-1291 C>G-MspI or rs1800544; -262 G>A-HhaI or rs1800544; 1780 C>T-DraI or rs553668) in 403 adult patients with ADHD assessed in relation to comorbidity and personality characteristics, as well as in 232 controls. The diagnosis followed DSM-IV criteria, and personality dimensions were evaluated with the Temperament and Character Inventory (TCI). There were no significant differences in allele and genotype frequencies between cases and controls. Patients carrying the G allele of rs1800544 presented lower scores in harm avoidance, and carriers of the T allele of rs553668 had more novelty seeking and less harm avoidance and persistence. Additionally, the haplotype carrying the G-G-T alleles (rs1800544-rs1800545-rs553668) was associated with lower scores in harm avoidance and persistence, and higher scores in novelty seeking compared to other haplotypes. These findings suggest that the conflicting findings obtained in association studies between ADRA2A polymorphisms and ADHD might be related to temperament profiles, and support additional studies addressing these effects in larger samples.

[Interrater reliability for diagnosis in adults of attention deficit hyperactivity disorder and oppositional defiant disorder using K-SADS-E]. / Concordância entre observadores para o diagnóstico em adultos do transtorno de déficit de atenção/hiperatividade e transtorno de oposição desafiante utilizando o K-SADS-E.

The diagnosis of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in adults lacks adequate assessment instruments. The aim of this investigation is to evaluate the interrater reliability of the sections of K-SADS-E adapted for the diagnosis of these disorders among adults. The adaptations were limited to asking questions directly to the patient, investigation of a later onset of symptoms, and asking for adult specific symptoms. Six trained raters scored 16 recorded interviews. Kappa coefficients were 1.00 for ADHD diagnosis in the past, 0.91 for subtype in the past, 1.00 for ADHD diagnosis in the present, 0.95 for subtype in the present, 1.00 and 0.89 for ODD diagnosis in the past and present, respectively (all with p < 0.001). These results reveal excellent agreement for the ADHD and ODD diagnosis in adults using the adapted form of the Portuguese version of K-SADS-E.

Pregnant crack addicts in a psychiatric unit / Gestantes dependentes de crack em uma unidade de internação psiquiátrica

OBJECTIVE: In this study we aim to characterize a sample of 85 pregnant crack addicts admitted for detoxification in a psychiatric inpatient unit. METHOD: Cross-sectional study. Sociodemographic, clinical, obstetric and lifestyle information were evaluated. RESULTS: Age of onset for crack use varied from 11 to 35 years (median = 21). Approximately 25% of the patients smoked more than 20 crack rocks in a typical day of use (median = 10; min-max = 1-100). Tobacco (89.4%), alcohol (63.5%) and marijuana (51.8%) were the drugs other than crack most currently used. Robbery was reported by 32 patients (41.2%), imprisonment experience by 21 (24.7%), trade of sex for money/drugs by 38 (44.7%), home desertion by 33 (38.8%); 15.3% were positive for HIV, 5.9% for HCV, 1.2% for HBV and 8.2% for syphilis. After discharge from the psychiatric unit, only 25% of the sample followed the proposed treatment in the chemical dependency outpatient service. CONCLUSION: Greater risky behaviors for STD, as well as high rates of maternal HIV and Syphilis were found. Moreover, the high rates of concurrent use of other drugs and involvement in illegal activities contribute to show their chaotic lifestyles. Prevention and intervention programs need to be developed to address the multifactorial nature of this problem.

OBJETIVO: Caracterizar uma amostra de 85 gestantes dependentes de crack admitidas para desintoxicação numa unidade de internação psiquiátrica. MÉTODO: Foram avaliadas, de forma transversal, variáveis sociodemográficas, clínico-obstétricas e informações sobre o seu estilo de vida. RESULTADOS: A idade de início de uso do crack variou dos 11 aos 35 anos (mediana = 21). Aproximadamente, 25% das pacientes fumavam mais de 20 pedras de crack em um dia típico de uso (mediana = 10; mín-máx = 1-100). Além do crack, as drogas mais utilizadas eram: tabaco (76; 89,4%), álcool (54; 63,5%) e maconha (44; 51,8%). Roubo foi relatado por 41,2% (32 pacientes), prisão por 24,7% (21), troca de sexo por dinheiro/drogas por 44,7% (38) e abandono do lar por 38,8% (33); 15,3% (13) tinham soropositividade para HIV, 5,9% (5) para HCV, 1,2% (1) para HBV e 8,2% (7) para sífilis. Após alta da unidade de internação psiquiátrica, somente 25% da amostra deram continuidade ao tratamento no ambulatório de dependência química. CONCLUSÃO: Comportamentos de risco para DSTs, altas taxas de HIV e sífilis, elevado uso de outras drogas e envolvimento em atividades ilegais fazem parte do estilo de vida caótico dessas mulheres. Programas de prevenção e intervenção dirigidos à natureza multifatorial dessa condição precisam ser desenvolvidos.

Transtorno de oposição e desafio e transtorno de conduta: os desfechos no TDAH em adultos / Oppositional defiant disorder and conduct disorder: their outcomes into adulthood

Os autores examinam a influência dos transtornos de oposição e desafio (TOD), de conduta (TC) e de personalidade anti-social (TPAS) ao longo da vida do indivíduo com TDAH. Os principais achados mostram que o TDAH é modulado por essas comorbidades e que seu prognóstico é modificado dependendo da presença ou não desses transtornos. O transtorno de oposição e desafio intensificaria as características de impulsividade e isolacionismo do TDAH, porém não acarretaria em um aumento na incidência de TPAS na vida adulta. Já o TC associado ao TDAH implica um aumento significativo na impulsividade e agressividade, estando associado significativamente a TPAS e um pior prognóstico. A diferenciação entre os diferentes transtornos e seu correto diagnóstico é essencial para o tratamento adequado do TDAH. Futuros estudos precisam determinar se o tratamento do TDAH produziria uma mudança significativa no prognóstico desse grupo de pacientes.

The authors examine the influence of oppositional defiant disorder (ODD), conduct disorder (CD) and anti-social personality disorder (ASPD) on attention deficit/hyperactivity disorder (ADHD) across life span. The findings showed that ADHD is modulated by this comorbidities and ADHD prognosis is modified depending on the presence or the absence of those disorders. ODD intensifies ADHD impulsivity and isolationism, but does not lead to an increase in the prevalence of ASPD in adulthood. Otherwise, CD associated with ADHD increases significantly the levels of impulsivity and aggressiveness, is associated with ASPD and a poor outcome. The appropriate approach to ADHD must be based on the correct diagnosis of different comorbidities to predict the outcomes. Further studies are needed to investigate if the treatment of ADHD can produce a significant improvement on the outcomes of this group of patients.

Concordância entre observadores para o diagnóstico em adultos do trantorno de déficit de atenção/hiperatividade e transtorno de oposição desafiante utilizando o K-SADS-E / Interrater reliability for diagnosis in adults of attention deficit hyperactivity disorder and oppositional defiant disorder using K-SADS-E

O diagnóstico do transtorno de déficit de atenção e hiperatividade (TDAH) e do transtorno de oposição desafiante (TOD) em adultos carece de instrumentos adequados. Esta investigação visa avaliar a confiabilidade entre observadores das seções do K-SADS-E adaptadas para os diagnósticos destes transtornos em adultos. As adaptações realizadas se limitaram ao direcionamento das perguntas ao próprio paciente, investigação do início dos sintomas em um período mais tardio e abordagem de sintomas próprios de adultos. Seis avaliadores treinados pontuaram 16 entrevistas gravadas. Os coeficientes Kappa foram de 1,00 para o diagnóstico de TDAH no passado, 0,91 para o subtipo no passado, 1,00 para diagnóstico de TDAH atual e 0,95 para o subtipo atual. Os coeficientes Kappa para o TOD foram de 1,00 para o diagnóstico no passado e 0,89 para o diagnóstico atual. Todos os coeficientes tiveram um p<0,001. Os resultados demonstram excelente concordância para os diagnósticos de TDAH e TOD em adultos utilizando a forma adaptada da versão em português do K-SADS-E.

Desenvolvimento emocional e uso de maconha / Emotional development paralysis and cannabis use

Neste artigo, é abordado o atraso no desenvolvimento emocional associado ao uso crônico de maconha. As implicações desta situação clínica são examinadas no contexto das terapias psicodinâmicas. Uma ilustração clínica é apresentada para demonstrar o impacto de algumas formas corriqueiras de abordagem do problema.

Pertubaçöes afetivas: o papel dos receptores / Affective disorders: the role of receptors

O uso crônico de antidepressores tricíclicos aumenta a sensibilidade dos receptores alfa-1 e receptores triptaminérgicos pós-sinápticos, diminuindo a sensibilidade dos receptores ß. O mecanismo destas alteraçöes näo está totalmente elucidado. Além disso, a relaçäo entre os receptores alfa - 2 e dopaminérgicos nas doenças mentais tem sido estudados, sem resultados conclusivos até o momento. Os autores revisam os trabalhos mais recentes acerca do papel destes receptores nas perturbaçöes afetivas

Transtorno por déficit de atençäo com hiperatividade e abuso de drogas na adolescência / Attention-deficit Hyperactivity Disorder and drug abuse in adolescence

Os autores discutem a importância clínica da persistencia do Transtorno por Déficit de Atençäo com Hiperatividade (TDAH) na adolescência e vida adulta e sua correlaçäo com o abuso de substancias psicoativas (SPA). A tendência a consolidaçäo do diagnóstico na nosografia internacional e ressaltada, bem como a abordagem terapêutica, na qual especial ênfase é dada ao uso de metilfenidato como farmaco de primeira escolha. O diagnóstico e o tratamento säo ilustrados com a apresentaço de casos clínicos

Morbidade psiquiátrica na populaçäo urbana de Porto Alegre / Psychiatric morbidity of urban population in Porto Alegre

O presente trabalho descreve a metodologia e os resultados do segmento de Porto Alegre, Rio Grande do Sul do Estudo Multicêntrico de Morbidade Neurológica e Psiquiátrica em Areas Urbanas Brasileiras. É a primeira experência em nosso meio de ampla investigaçäo de diagnósticos psiquiátricos em populaçöes urbanas. Realizada de julho de 1990 a janeiro de 1991, determinou através de um instrumento de screening (QMPA), na sua 1§ fase, e com IS-DSM-III na 2§ fase, a prevalência de diagnósticos psiquiátricos nesta populaçäo. A prevalência estimada de morbidade psiquiátrica nessa amostra foi de 49 por cento, sendo os três diagnósticos mais frequentemente encontrados: transtornos do uso de substâncias psicoativas (24,6 por cento), transtornos de ansiedade (23 por cento) e transtornos afetivos (10,7 por cento)

Morbidade psiquiátrica na populaçäo urbana de Porto Alegre / Psychiatric morbidity on the urban population in the city of Porto Alegre

O presente trabalho descreve a metodologia e os resultados do segmento de Porto Alegre, Rio Grande do Sul do Estudo Multicêntrico de Morbidade Neurológica e Psiquiátrica em Areas Urbanas Brasileiras. É a primeira experiência em nosso meio de ampla investigaçäo de diagnósticos psiquiátricos em populaçöes urbanas. Realizada de julho de 1990 a janeiro de 1991, determinou, através de um instrumento de screening (QMPA), na sua 1ª fase, e com IS-DSM-III na 2ª fase, a prevalência de diagnósticos nesta populaçäo. A prevalência estimada de morbidade psiquiátrica nessa amostra foi de 49//, sendo os três diagnósticos mais frequentemente encontrados: transtornos do uso de substâncias psicoativas (24,6//), transtornos de ansiedade (23//) e transtornos afetivos (10,7//)