Paulo Mattos

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

BACKGROUND Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. FINDINGS Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohens d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohens d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). INTERPRETATION With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING National Institutes of Health.

Apresentação de uma versão em português para uso no Brasil do instrumento MTA-SNAP-IV de avaliação de sintomas de transtorno do déficit de atenção/hiperatividade e sintomas de transtorno desafiador e de oposição

The SNAP-IV questionnaire was developed to evaluate symptoms of attention-deficit/hyperactivity disorder in children and adolescents. It can be fulfilled by parents or teachers and consists of the symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for attention-deficit/hyperactivity disorder (criterion A) and oppositional-defiant disorder. OBJECTIVES: To develop a version of the SNAP-IV used in the Multimodal Treatment Assessment Study to be applied in Brazil. METHODS: Translation, back-translation, evaluation of semantic equivalence, debriefing and definition of a final version was the methodology used to reach an adequate version. RESULTS: After translation and back-translation, 20 items were considered similar, six items were considered approximate in meaning, and five items were considered different from the original instrument in English. The final version was chosen considering many aspects, including similarity to the original version, ease of understanding and level of equivalence of the terms in different regions of the country. CONCLUSION: The Portuguese version of the SNAP-IV will allow the screening of attention-deficit/hyperactivity disorder and oppositional-defiant disorder in a similar manner to the original version.

Neuropsicologia dos transtornos alimentares: revisão sistemática da literatura

BACKGROUND The pathophysiology of eating disorders is still unknown, with many factors possibly involved. The existence of a central nervous system (CNS) dysfunction is being investigated with particular interest. One of the most employed strategies to reach this goal is the evaluation of cognitive functioning of patients with eating disorders with neuropsychological tests. OBJECTIVE To evaluate the current knowledge about the neuropsychology of ED. METHODS We performed a review of several data bases (including MedLINE, PsychoINFO, LILACS and Cochrane Data Bank), using terms related to main theme of interest. The review comprised articles published up to January, 2004. RESULTS Anorexia Nervosa (AN) was the most studied ED from the neuropsychological point-of-view, with studies tending to elicit attentive, visuo-spatial, and visuo-constructive deficits among such patients. On the other side, patients with Bulimia Nervosa (BN) exhibited deficits in the selective aspects of attention and in executive functions. As yet, there is no study covering the neuropsychological aspects of binge-eating disorder. After successful treatment, individuals show improvement of some cognitive deficits, while other seem to persist. CONCLUSIONS The ED are possibly associated with a certain degree of neuropsychological dysfunction, even though there is no consensus with regard to which function is particularly impaired. The fact that some cognitive dysfunction tend to disappear after treatment argues in favor of the hypothesis that these are functional deficits. Other deficits, however, tend to persist, suggesting that they may precede the development of eating disorders or even contribute to their development or to a worse prognosis. The study of the neuropsychological aspects of ED may help tailoring more selective therapeutic approaches to patients suffering from these disorders.

Adaptação transcultural para o português da escala Adult Self-Report Scale para avaliação do transtorno de déficit de atenção/hiperatividade (TDAH) em adultos

The criteria listed in the fourth edition of the Diagnostic and Statistical Manual (DSM-IV) from the American Psychiatric Association are the most used ones for the diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD) being based on field studies with children and adolescents. The Adult Self-Report Scale (ASRS, version 1.1) was developed to adapt those symptoms to an adult life context. The present study consisted of a transcultural adaptation of the original instrument in English into a final version to be used in Brazil. Results indicated a satisfactory equivalence between versions, with some modifications being done after debriefing, supporting the importance of this step in studies like this.

Altered Functional Brain Connectivity in a Non-Clinical Sample of Young Adults with Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and hyperactivity/impulsivity that often persist in adulthood. There is a growing consensus that ADHD is associated with abnormal function of diffuse brain networks, but such alterations remain poorly characterized. Using resting-state functional magnetic resonance imaging, we characterized multivariate (complex network measures), bivariate (network-based statistic), and univariate (regional homogeneity) properties of brain networks in a non-clinical, drug-naive sample of high-functioning young men and women with ADHD (nine males, seven females) and a group of matched healthy controls. Data from our sample allowed the isolation of intrinsic functional connectivity alterations specific to ADHD diagnosis and symptoms that are not related to developmental delays, general cognitive dysfunction, or history of medication use. Multivariate results suggested that frontal, temporal, and occipital cortices were abnormally connected locally as well as with the rest of the brain in individuals with ADHD. Results from the network-based statistic support and extend multivariate results by isolating two brain networks comprising regions between which inter-regional connectivity was significantly altered in the ADHD group; namely, a frontal amygdala-occipital network and a frontal temporal-occipital network. Brain behavior correlations further highlighted the key role of altered orbitofrontal-temporal and frontal-amygdala connectivity for symptoms of inattention and hyperactivity/impulsivity. All univariate properties were similar between groups. Taken together, results from this study show that the diagnosis and the two main symptom dimensions of ADHD are related to altered intrinsic connectivity in orbitofrontal-temporal-occipital and fronto-amygdala-occipital networks. Accordingly, our findings highlight the importance of extending the conceptualization of ADHD beyond segregated fronto-striatal alterations.

International Variation in Treatment Procedures for ADHD: Social Context and Recent Trends

OBJECTIVE Scientific and clinical interest in attention-deficit hyperactivity disorder (ADHD) is increasing worldwide. This article presents data from a cross-national workshop and survey related to questions of variability in diagnostic and, particularly, treatment procedures. METHODS Representatives of nine nations (Australia, Brazil, Canada, China, Germany, Israel, the Netherlands, Norway, and the United Kingdom), plus the United States, who attended a 2010 workshop on ADHD, responded to a survey that addressed diagnostic procedures for ADHD; treated prevalence of medication approaches, as well as psychosocial interventions; types of medications and psychosocial treatments in use; payment systems; beliefs and values of the education system; trends related to adult ADHD; and cultural and historical attitudes and influences related to treatment. RESULTS Use of both medication and psychosocial treatment for ADHD varies widely within and across nations. More expensive long-acting formulations of medications are becoming more widespread. Nations with socialized medical care provide a wide array of evidence-based interventions. Economic, historical, and political forces and cultural values are related to predominant attitudes and practices. Strong antipsychiatry and antimedication voices remain influential in many nations. CONCLUSIONS There is considerable variation in implementation of care for ADHD. Recognition of the social context of ADHD is an important step in ensuring access to evidence-based interventions for this prevalent, chronic, and impairing condition.

Attention-deficit/hyperactivity disorder and comorbidity in Brazil: Comparisons between two referred samples

Abstract.Objective:The aim of this study was to compare the pattern of comorbidity in referred samples of Attention-Deficit/Hyperactivity Disorder (ADHD) patients from two different geographic areas in Brazil.Methods:The diagnoses of ADHD and comorbid conditions, according to DSM-IV criteria, were achieved in both clinics through semi-structured interview methodology, complemented by clinical interviews with the children or adolescents and their parents.Results:We assessed 343 ADHD children and adolescents in Porto Alegre (capital of the southernmost state of the country) and 78 ADHD youths in Rio de Janeiro (capital of a southestern state). Although a significant difference in the prevalence of ADHD without comorbidity was detected between the two groups (p = 0.02), no significant difference was detected in the profile of comorbidities between them. Main ADHD comorbidities in both samples were: a) Oppositional Defiant Disorder (Porto Alegre = 39.1%; Rio de Janeiro = 51.3 %); b) Anxiety Disorders (Porto Alegre = 24.2%; Rio de Janeiro = 30.8 %); c) Conduct Disorder (Porto Alegre = 13.7%; Rio de Janeiro = 17.9 %); and d) Major Depression and/or Dysthymia (Porto Alegre = 11.4%; Rio de Janeiro = 10.3 %).Conclusions:Our results from clinical samples in a developing country with a diverse culture suggest the crosscultural validity of the ADHD comorbidity profile.

Memory complaints and test performance in healthy elderly persons

In order to compare the use of a structured self-report questionnaire with direct questioning about memory problems, 71 healthy and independent aged individuals (63 women) from the community without risk factors for cognitive deficits were objectively asked about subjective memory complaints (SMC), given the Memory Complaint Questionnaire (MAC-Q) and then submitted to the Rey Auditory Verbal Learning Test (RAVLT). SMC positively correlated with higher scores on MAC-Q, although a significant percentage of the sample had SMC and lower scores on MAC-Q and also no SMC and higher scores on MAC-Q. Performance on RAVLT was significantly worse (p<0.05) for the group presenting SMC but not for the group with higher scores on the MAC-Q. We conclude that direct questioning maybe more clinically significant than a self report questionnaire, at least for elderly persons from the community without risk factors for cognitive decline or depression.

Review of literature of attention-deficit/hyperactivity disorder with comorbid eating disorders

OBJECTIVE According to studies of prevalence, up to 70% of adults with attention deficit/hyperactivity disorder have at least one psychiatric comorbidity, which leads to diagnostic and therapeutic difficulties as well as more severe functional impairment. There is a paucity of data on the comorbidity of attention deficit/hyperactivity disorder and eating disorders. The objective of this study was to review the literature regarding the attention deficit/hyperactivity disorder/eating disorders comorbidity, performing a critical analysis of relevant data. METHOD Articles in Medline, Lilacs, SciELO, ISI and PsycINFO databases from 1980 up to 2008, were searched. The references from the articles were used as additional sources of data. RESULTS Fourteen articles were found: five prevalence studies, four case reports, three case-control studies, one symptom-assessment study of attention deficit/hyperactivity disorder and eating disorders, and one article regarding possible causes of the association between attention deficit/hyperactivity disorder and eating disorders. These articles suggested that adult women with attention deficit/hyperactivity disorder are at higher risk of developing eating disorders, especially bulimia nervosa. Bulimia Nervosa rates found in attention deficit/hyperactivity disorder groups ranged from 1% to 12%, versus 0% to 2% in control groups. CONCLUSIONS Although there seems to be a relationship between attention deficit/hyperactivity disorder and eating disorders, the reduced number of studies available, with various methodologies, and small sample sizes limit the generalization of the findings.

Transtornos alimentares comórbidos em uma amostra clínica de adultos com transtorno do déficit de atenção com hiperatividade

Although comorbidity between attention-deficit/hyperactivity disorder (ADHD) and eating disorders (ED) is relevant for clinical treatment, it is seldom investigated. METHODS: 86 DSM-IV attention deficity hyperactivity disorder patients out of 107 self-referred adults in a specialized center for attention deficity hyperactivity disorder were interviewed using SCID-R to evaluate the lifetime prevalence of ED and other comorbid conditions. RESULTS: Nine attention deficity hyperactivity disorder patients had comorbid eating disorders; binge eating disorder (BED) was the most common diagnosis. The group with eating disorders presented a higher prevalence of other comorbid disorders (p=0.02). No significant differences were found on gender, age at assessment, schooling level and type of attention deficity hyperactivity disorder between groups. CONCLUSION: Attention deficity hyperactivity disorder clinical samples may have a high prevalence of BED comorbidity. Patients with attention deficity hyperactivity disorder and eating disorders may have a different comorbid profile.