Outcomes of a 12-week ecologically valid observational study of first treatment with methylphenidate in a representative clinical sample of drug naïve children with ADHD

Randomized placebo-controlled trials have reported efficacy of methylphenidate (MPH) for Attention-deficit/hyperactivity disorder (ADHD); however, selection biases due to strict entry criteria may limit the generalizability of the findings. Few ecologically valid studies have investigated effectiveness of MPH in representative clinical populations of children. This independently funded study aims to describe treatment responses and their predictors during the first 12 weeks of MPH treatment using repeated measurements of symptoms and adverse reactions (ARs) to treatment in 207 children recently diagnosed with ADHD. The children were consecutively included from the Child and Adolescent Mental Health Centre, Mental Health Services, The Capital Region of Denmark. The children (mean age, 9.6 years [range 7–12], 75.4% males) were titrated with MPH, based on weekly assessments of symptoms (18-item ADHD-rating scale scores, ADHD-RS-C) and ARs. At study-end 187 (90.8%) children reached a mean end-dose of 1.0 mg/kg/day. A normalisation/borderline normalisation on ADHD-RS-C was achieved for 168 (81.2%) children on the Inattention and/or the Hyperactivity-Impulsivity subscale in week 12, and 31 (15.0%) children were nonresponders, which was defined as absence of normalisation/borderline normalisation (n = 19) or discontinuation due to ARs (n = 12), and eight (3.8%) children dropped out from follow-up. Nonresponders were characterised by more severe symptoms of Hyperactivity-Impulsivity and global impairment before the treatment. ARs were few; the most prominent were appetite reduction and weight loss. A decrease in AR-like symptoms during the treatment period questions the validity of currently available standard instruments designed to measure ARs of MPH. This ecologically valid observational study supports prior randomized placebo-controlled trials; 81.2% of the children responded favourably in multiple domains with few harmful effects to carefully titrated MPH. Clinical trial registration: ClinicalTrials.gov with registration number NCT04366609

Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen’s d=−0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis

Romantismo e objetividade: notas sobre um panorama do Rio de Janeiro

The article deals with the great Panorama of Rio de Janeiro exhibited in Paris, 1824, and its sources - a series of watercolours which have also generated succeeding engravings produced dur-ing the 1830s. Panoramas, in their early formal conventions are shown to interplay with Romanticism's and Naturphilosophie's theses and to put in motion the legacy of 11th-century paint-ing . As this geme of visual device develops, Rio's watercoulours display symptoms of a gradual dismissal of its initial ambilions, through lhe treatment of the natural site and the city. At last the invention of the daguerreotype and vai d'oiseau urban images, among other traits, signale the changes in sensibility related to the production and consumption of those circular canvasses. From 1840/50 on panoramas conceived by the will to fuse art and science and bya reflection on nature and liberty turn essentially into a mass entertainment.Romantismo e objetividade: notas sobre um panorama do Rio de Janeiro Margarelh da Silva Pereira Enfoca O grande Panorama do Rio de Janeiro, exibido em Paris em 1824, do qual se conhece a série de aquarelas que serviram de base tanto àquela ampliação quanto às sucessivas gravuras da cena que foram produzidas na década de 1830. Busca-se mostrar como os panoramas em sua formalização inicial dialogam com as teses do romantismo e da Naturphilosophie, mobilizan-do heranças da pintura seiscentista. No desenvolvimento desta forma de exibição as aquarelas do Rio apresentam sintomas do gradual afastamento das ambições iniciais através do tratamento dispensado ao sítio natural e à cidade. Por fim, a invenção do daguerreótipo, e as vistas urbanas em võo de pássaro, enlre outros, balizariam a mudança de sensibilidade na produção e na fruição dessas telas circulares. A partir de 1840/50 os panoramas engendrados pelo desejo de fusão entre arte e ciência e pela reflexão sobre a natureza e a liberdade, tornar-se-iam, sobretudo, um divertimento de massas

Structural asymmetry of the human cerebral cortex: Regional and between-subject variability of surface area, cortical thickness, and local gyrification

Structural asymmetry varies across individuals, brain regions, and metrics of cortical organization. The current study investigated regional differences in asymmetry of cortical surface area, thickness, and local gyrification, and the extent of between-subject variability in these metrics, in a sample of healthy young adults (N = 200). Between-subject variability in cortical structure may provide a means to assess the extent of biological flexibility or constraint of brain regions, and we explored the potential influence of this variability on the phenotypic expression of structural asymmetry. The findings demonstrate that structural asymmetries are nearly ubiquitous across the cortex, with differing regional organization for the three cortical metrics. This implies that there are multiple, only partially overlapping, maps of structural asymmetry. The results further indicate that the degree of asymmetry of a brain region can be predicted by the extent of the region’s between-subject variability. These findings provide evidence that reduced biological constraint promotes the expression of strong structural asymmetry

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait

Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders

Order and culture. Passages of popularization

I will try to draw a portrait of the political genesis of the museum as a popular institution for national thought and education by examining Europe's first National Museums: the British Museum, the Louvre, the Versailles Museum of the History of France and those museums characterized by an early expression of nationalist feeling before the political institution of the nation state emerged. Their influence grew from enlightened philosophy and they became, in spite of their aspiration of objectivity, major teachers of minor and later pupils.

Danser avec les chevaux

La représentation d’un carrousel marquait l’apogée des festivités d’une cour absolutiste. Les souverains européens s’y affrontaient dans des spectacles équestres à grands frais, avec des balletti a cavalli, afin d’affirmer leur pouvoir et de diffuser leur gloire et leur splendeur à travers les cours européennes.Dans ces exercices équestres représentés publiquement et faisant référence aux festivités équestres de l’Antiquité, le monarque et la noblesse donnaient la preuve de leur hardiesse, de leur adresse à cheval comme l’exigeait la guerre en tant que pratique aristocratique par excellence. Les descriptions des triomphes romains influencèrent fortement les entrées royales à la Renaissance et à l’époque baroque mais aussi les carrousels avec cavaliers, soldats à pied et musiciens, leurs costumes et leur équipement. Au XVIIe siècle, les courses de bague ou les joutes de tête « à la turc » maintinrent les cavaliers en forme physique pour la guerre. En 1776, Marie-Antoinette fit installer comme nouveau divertissement à la cour un manège dans les jardins du Grand Trianon. Les courtisans, désormais inaptes à la guerre mais installés confortablement sur des chevaux de bois, frappaient des bagues attachées à des lanternes en papier (jeu de bague à la chinoise) ; ainsi, des cérémonies équestres de haute voltige se transformèrent en chevaux tournant mécaniquement autour d’un pivot. La conséquence en fut que les carrousels survécurent après le déclin de la culture de cour à partir du XIXe siècle dans les manèges des foires populaires.The presentation of a carrousel at the court of an absolute monarch was the culminating feature of a festive occasion. European sovereigns competed to perform equestrian shows at great expense, using balletti a cavalli to assert their power, to proclaim their glory and splendour throughout the courts of Europe.In these publicly presented horse riding exercises, monarchs and nobility displayed the boldness and skillfulness on horseback necessary in war, an aristocratic exercise par excellence and one which was a reference to the equestrian festivities of Antiquity. Descriptions of Roman triumphal parades strongly influenced royal entries during the Renaissance and the Baroque period as well as the carrousels performed with horse riders, foot soldiers and musicians, their costumes and their equipment. In the 17th century, competitions of ring- or Turk’s-head jousting kept the horsemen physically fit for warfare. In 1776, as a new entertainment at court, Queen Marie-Antoinette had a manège installed in the gardens of the Grand Trianon at Versailles. Courtiers, no longer fit enough to go to war but comfortably seated on wooden horses, hit rings attached to Chinese paper lanterns (jeu de bague à la chinoise); in this way, high-level equestrian celebrations were transformed into horses turning mechanically around a pivot. The outcome was that carrousels have survived (following the decline of court culture in the 19th century) in the form of popular roundabouts at public fairs