Background The ‘New Forest Parenting Package’ (NFPP), an 8-week home-based intervention for parents of preschoolers with ADHD, fosters constructive parenting to target ADHD-related dysfunctions in attention and impulse control.Although NFPP has improved parent and laboratory measures of ADHD in community samples of children with ADHD-like problems, its efficacy in a clinical sample, and relative to an active treatment comparator, is unknown. The aims are to evaluate the short and long-term efficacy and generalization effects of NFPP compared to an established clinic-based parenting intervention for treating noncompliant behavior (‘Helping the Noncompliant Child’ [HNC]) in young children with ADHD. Methods A randomized controlled trial with three parallel arms was the design for this study. 164 3-4-year-olds, 73.8% male, meeting DSM-IV ADHD diagnostic criteria were randomized to NFPP (N = 67), HNC (N = 63), or wait-list control (WL, N = 34). All participants were assessed at post-treatment. NFPP and HNC participants were assessed at follow-up in the next school year. Primary outcomes were ADHD ratings by teachers blind to and uninvolved in treatment, and by parents. Secondary ADHD outcomes included clinician assessments, and laboratory measures of on-task behavior and delay of gratification. Other outcomes included parent and teacher ratings of oppositional behavior, and parenting measures. (Trial name: Home-Based Parent Training in ADHD Preschoolers; Registry: ClinicalTrials.gov Identifier: NCT01320098; URL: http://www/clinicaltrials.gov/ct2/show/NCT01320098). Results In both treatment groups, children's ADHD and ODD behaviors, as well as aspects of parenting, were rated improved by parents at the end of treatment compared to controls. Most of these gains in the children's behavior and in some parenting practices were sustained at follow-up. However, these parent-reported improvements were not corroborated by teacher ratings or objective observations. NFPP was not significantly better, and on a few outcomes significantly less effective, than HNC. Conclusions The results do not support the claim that NFPP addresses putative dysfunctions underlying ADHD, bringing about generalized change in ADHD, and its underpinning self-regulatory processes. The findings support documented difficulties in achieving generalization across non-targeted settings, and the importance of using blinded measures to provide meaningful assessments of treatment effects.

Despite the common co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) in individuals with autism spectrum disorders (ASD), the underlying mechanisms are under-explored. A potential candidate for investigation is response time intra-subject variability (RT-ISV), a hypothesized marker of attentional lapses. Direct comparisons of RT-ISV in ASD versus ADHD are limited and contradictory. We aimed to examine whether distinct fluctuations in RT-ISV characterize children with ASD and with ADHD relative to typically developing children (TDC). We applied both a priori-based and data-driven strategies to RT performance of 46 children with ASD, 46 with ADHD, and 36 TDC (aged 7–11.9 years). Specifically, we contrasted groups relative to the amplitude of four preselected frequency bands as well as to 400 frequency bins from 0.006 to 0.345 Hz. In secondary analyses, we divided the ASD group into children with and without substantial ADHD symptoms (ASD+ and ASD−, respectively). Regardless of the strategy employed, RT-ISV fluctuations at frequencies between 0.20 and 0.345 Hz distinguished children with ADHD, but not children with ASD, from TDC. Children with ASD+ and those with ADHD shared elevated amplitudes of RT-ISV fluctuations in frequencies between 0.18 and 0.345 Hz relative to TDC. In contrast, the ASD− subgroup did not differ from TDC in RT-ISV frequency fluctuations. RT-ISV fluctuations in frequencies 0.18–0.345 Hz (i.e., periods between 3 and 5 s) are associated with ADHD symptoms regardless of categorical diagnosis and may represent a biomarker. These results suggest that children with ADHD and those with ASD+ share common underlying pathophysiological mechanisms of RT-ISV.

An increasingly important goal of psychiatry is the use of brain imaging data to develop predictive models. Here we present two contributions to statistical methodology for this purpose. First, we propose and compare a set of wavelet-domain procedures for fitting generalized linear models with scalar responses and image predictors: sparse variants of principal component regression and of partial least squares, and the elastic net. Second, we consider assessing the contribution of image predictors over and above available scalar predictors, in particular via permutation tests and an extension of the idea of confounding to the case of functional or image predictors. Using the proposed methods, we assess whether maps of a spontaneous brain activity measure, derived from functional magnetic resonance imaging, can meaningfully predict presence or absence of attention deficit/hyperactivity disorder (ADHD). Our results shed light on the role of confounding in the surprising outcome of the recent ADHD-200 Global Competition, which challenged researchers to develop algorithms for automated image-based diagnosis of the disorder.

We propose a penalized spline approach to performing large numbers of parallel non-parametric analyses of either of two types: restricted likelihood ratio tests of a parametric regression model versus a general smooth alternative, and nonparametric regression. Compared with naïvely performing each analysis in turn, our techniques reduce computation time dramatically. Viewing the large collection of scatterplot smooths produced by our methods as functional data, we develop a clustering approach to summarize and visualize these results. Our approach is applicable to ultra-high-dimensional data, particularly data acquired by neuroimaging; we illustrate it with an analysis of developmental trajectories of functional connectivity at each of approximately 70000 brain locations. Supplementary materials, including an appendix and an R package, are available online.

We compared the expression of phenotype of parvalbumin (PV)-immunoreactive cells in the prefrontal cortex (PFC) of juvenile rats reared in enriched environment (EE) after daily intermittent hypoxia (IH) exposure to those reared in standard environment (SE) and investigated the involvement of NADPH oxidase-2 (NOX2)-derived oxidative stress in the IH-induced neurodevelopmental and neurobehavioral consequences in a juvenile rat model of obstructive sleep apnea. Postnatal day 21 (P21) rats were exposed to IH or room air 8 h daily for 14 consecutive days. After the daily exposure, the rats were raised in SE or EE. In the PFC of P34 rats, we determined the impact (i) of IH exposures on NOX2-derived oxidative stress and PV immunoreactivity, (ii) of pharmacological NOX2 inhibition on IH-induced oxidative stress and PV immunoreactivity, and (iii) of EE on the IH-induced oxidative stress and PV immunoreactivity. Behavioral testing of psychiatric anxiety was carried out consecutively in the open-field test and elevated plus maze at P35 and P36. The results showed IH exposures increased NOX2 expression in the PFC of P34 rats, which was accompanied with elevation of NOX activity and indirect markers of oxidative stress (4-HNE). IH exposures increased 4-HNE immunoreactivity in cortical PV cells, which was accompanied with reduction of PV immunoreactivity. Treatment of IH rats with the antioxidant/NOX inhibitor apocynin prevented the PV cells loss in the PFC and reversed the IH-induced psychiatric anxiety. EE attenuated the NOX2-derived oxidative stress and reversed the PV-immunoreactivity reduction in the PFC induced by IH. Our data suggest that EE might prevent the juvenile hypoxia-induced developmental loss of PV cells in the PFC and attenuate the neurobehavioral alterations through inhibition of NOX2-derived oxidative stress.