Training Executive, Attention, and Motor Skills (TEAMS): a Preliminary Randomized Clinical Trial of Preschool Youth with ADHD.

This preliminary randomized controlled trial compared Training Executive, Attention and Motor Skills (TEAMS), a played-based intervention for preschool children with attention-deficit/hyperactivity disorder (ADHD), to an active comparison intervention consisting of parent education and support (ClinicalTrials.gov Identifier: NCT01462032). The primary aims were to gauge preliminary efficacy and assist in further development of TEAMS. Four- and 5-year-old children with ADHD were randomly assigned to receive TEAMS (N = 26) or the comparison intervention (N = 26) with blinded assessments by parents, teachers and clinicians ascertained pretreatment, post-treatment, and 1- and 3-months post-treatment. Changes in ADHD severity, impairment, parenting factors, and neuropsychological functioning over time as a function of treatment condition were assessed using the PROC MIXED procedure in SAS. Across most measures, significant main effects for Time emerged; both treatments were associated with reduced ADHD symptoms that persisted for three months post-treatment. There were no significant Treatment effects or Time x Treatment interactions on symptom and impairment measures, suggesting that the magnitude of improvement did not differ between the two interventions. However, significant correlations emerged between the magnitude of behavioral change, as assessed by parents and clinicians, and the amount of time families engaged in TEAMS-related activities during treatment. Across a wide array of parenting and neuropsychological measures, there were few significant group differences over time. TEAMS and other psychosocial interventions appear to provide similar levels of benefit. Play-based interventions like TEAMS represent a potentially viable alternative/addition to current ADHD treatments, particularly for young children, but more research and further development of techniques are necessary.

De novo SCN2A splice site mutation in a boy with Autism spectrum disorder.

BACKGROUND: SCN2A is a gene that codes for the alpha subunit of voltage-gated, type II sodium channels, and is highly expressed in the brain. Sodium channel disruptions, such as mutations in SCN2A, may play an important role in psychiatric disorders. Recently, de novo SCN2A mutations in autism spectrum disorder (ASD) have been identified. The current study characterizes a de novo splice site mutation in SCN2A that alters mRNA and protein products. CASE PRESENTATION: We describe results from clinical and genetic characterizations of a seven-year-old boy with ASD. Psychiatric interview and gold standard autism diagnostic instruments (ADOS and ADI-R) were used to confirm ASD diagnosis, in addition to performing standardized cognitive and adaptive functioning assessments (Leiter-R and Vineland Adaptive Behavior Scale), and sensory reactivity assessments (Sensory Profile and Sensory Processing Scales). Genetic testing by whole exome sequencing revealed four de novo events, including a splice site mutation c.476 + 1G > A in SCN2A, a missense mutation (c.2263G > A) causing a p.V755I change in the TLE1 gene, and two synonymous mutations (c.2943A > G in the BUB1 gene, and c.1254 T > A in C10orf68 gene). The de novo SCN2A splice site mutation produced a stop codon 10 amino acids downstream, possibly resulting in a truncated protein and/or a nonsense-mediated mRNA decay. The participant met new DSM-5 criteria for ASD, presenting with social and communication impairment, repetitive behaviors, and sensory reactivity issues. The participant's adaptive and cognitive skills fell in the low range of functioning. CONCLUSION: This report indicates that a splice site mutation in SCN2A might be contributing to the risk of ASD. Describing the specific phenotype associated with SCN2A mutations might help to reduce heterogeneity seen in ASD.

Changes in ADHD symptom endorsement: preschool to school age.

To investigate endorsement patterns among the 18 DSM-IV symptoms of ADHD in a longitudinal sample of children with and without ADHD (n = 144), as assessed at ages 4-5, 5-6, and 6-7 years. Symptom endorsements and diagnoses were determined at all time-points via K-SADS-PL interview administered to parents and supplemented by teacher questionnaires and clinician observations. Changes in endorsement patterns over time for each of the 18 DSM-IV symptoms were ascertained. Several symptoms, particularly those of inattention, were infrequently endorsed and of apparently limited diagnostic utility at ages 4-5; hyperactive/impulsive symptoms were more frequently endorsed among young children with ADHD than were inattentive symptoms. However, by ages 6-7, inattention items were somewhat superior at discriminating ADHD from Non-ADHD children. Several DSM-IV and now DSM-V symptoms provide limited diagnostic differentiation prior to school-age, particularly those most commonly observed in the context of formal schooling. Consideration should be made in future iterations of the DSM that account for such developmental and contextual differences.

Preventive interventions for ADHD: a neurodevelopmental perspective.

It is proposed that the time is ripe for the development of secondary preventive interventions for attention-deficit/hyperactivity disorder (ADHD). By targeting preschool children, a developmental stage during which ADHD symptoms first become evident in most children with the disorder, many of the adverse long-term consequences that typify the trajectory of ADHD may be avoided. A dynamic/interactive model of the biological and environmental factors that contribute to the emergence and persistence of ADHD throughout the lifespan is proposed. Based on this model, it is argued that environmental influences and physical exercise can be used to enhance neural growth and development, which in turn should have an enduring and long-term impact on the trajectory of ADHD. Central to this notion are 2 hypotheses: 1) environmental influences can facilitate structural and functional brain development, and 2) changes in brain structure and function are directly related to ADHD severity over the course of development and the degree to which the disorder persists or remits with time. We present experimental and correlational data supporting the first hypothesis and longitudinal data in individuals with ADHD supporting the second. The case is made for initiating such an intervention during the preschool years, when the brain is likely to be more "plastic" and perhaps susceptible to lasting modifications, and before complicating factors, such as comorbid psychiatric disorders, academic failure, and poor social and family relationships emerge, making successful treatment more difficult. Finally, we review recent studies in young children with ADHD that might fall under the umbrella of secondary prevention.