Background: Although both emotion and response inhibition are thought to be important in attention-deficit/hyperactivity disorder (ADHD), little is known about the neural mechanisms that underlie the interaction between these two processes in patients with this disorder. This study aimed at examining how emotional contexts affect inhibitory control in children with ADHD.Method: A total of 24 ADHD children and 24 healthy comparison subjects performed a modified go/no-go task during three different emotionally laden contexts: negative, neutral and positive. To explore the timing and the underlying neural substrates of emotion-modulated response inhibition, event-related potentials were measured and further analysed both at the scalp and at the voxel level.Results: Patients with ADHD showed greater activation of inhibition-related neural mechanisms (i.e. no-go P3 amplitudes and orbitofrontal cortex activity) to maintain a similar level of performance as healthy comparison subjects, especially during the emotionally arousing contexts (negative and positive).Conclusions: This study provides plausible neural mechanisms for the difficulty that ADHD children have in controlling their behaviour in highly emotional situations. Such emotional contexts might increase the need for top-down inhibitory control and put ADHD children at greater risk for impulsive behaviours and emotional dysregulation.

SLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of clinical features of patients with SLITRK2 variants. Furthermore, impaired excitatory synapse maintenance induced by hippocampal CA1-specific cKO of Slitrk2 caused abnormalities in spatial reference memory. Collectively, these data suggest that SLITRK2 is involved in X-linked neurodevelopmental disorders that are caused by perturbation of diverse facets of SLITRK2 function.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorder.