Reduced ADHD symptoms at adolescence may not lead to decreased risks for psychiatric comorbidity, and identification of severe ADHD symptoms at childhood and age-specific comorbid patterns throughout the developmental stage is important to offset the long-term adverse psychiatric outcomes of ADHD.

SUMMAR Y This study aimed to investigate the association between attention-deficit hyperactivity disorder (ADHD) symptoms and subtypes, and sleep schedules, daytime inadvertent napping, and sleep problems ⁄ disorders in children and adolescents with and without ADHD. The sample included 325 patients with ADHD, aged 10-17 years [male: 81.5%; combined type (ADHD-C): 174; predominantly inattentive type (ADHD-I): 130; predominantly hyperactive-impulsive type (ADHD-HI): 21], and 257 children and adolescents without lifetime ADHD (non-ADHD). We conducted psychiatric interviews with the participants and their mothers before making the diagnoses of ADHD, other psychiatric disorders, and sleep problems or disorders. We also collected the medication treatment data and parent and teacher reports of ADHD symptoms. Multilevel models were used for data analyses controlling for sex, age, psychiatric comorbidities, and treatment with methylphenidate. The ADHD-C and ADHD-I groups had more daytime inadvertent napping. In general, the three subtypes were associated with increased rates of sleep problems ⁄ disorders. Specifically, ADHD-C rather than ADHD-I was associated with circadian rhythm problems, sleep-talking, nightmares (also ADHD-HI), and ADHD-I was associated with hypersomnia. The most-related sleep schedules and problems for inattention and hyperactivity-impulsivity were earlier bedtime, later rise time, longer nocturnal sleep, more frequent daytime napping, insomnia, sleep terrors, sleep-talking, snoring, and bruxism across informants. The findings imply that in addition to the dichotomous approach of ADHD and considering the psychiatric comorbid conditions, ADHD subtypes and symptom dimensions need to be considered in clinical practice and in the research regarding the association between ADHD and sleep problems ⁄ disorders.k e y w o r d s adolescent, attention-deficit hyperactivity disorder subtype, attentiondeficit hyperactivity disorder symptoms, sleep problems ⁄ disorders, sleep schedules

BackgroundNeuroanatomical differences between individuals with and without autism spectrum disorder (ASD) were inconsistent in the literature. Such heterogeneity may substantially originate from age-differential effects.MethodsVoxel-based morphometry was applied in 86 males with ASD and 90 typically developing control (TDC) males (aged 7 to 29 years). Three steps of statistical modeling (model 1, multiple regression with age as a covariate; model 2, multiple regression further considering diagnosis-by-age interaction; model 3, age-stratified analyses) were performed to dissect the moderating effects of age on diagnostic group differences in neuroanatomy.ResultsAcross ages, males with and without ASD did not differ significantly in total gray matter (GM) or white matter (WM) volumes. For both groups, total GM volumes decreased and WM volumes increased with age. For regional volume, comparing with the model only held the age constant (model 1), the main effect of group altered when diagnosis-by-age interaction effects were considered (model 2). Here, participants with ASD had significantly greater relative regional GM volumes than TDC in the right inferior orbitofrontal cortex and bilateral thalamus; for WM, participants with ASD were larger than TDC in the bilateral splenium of corpus callosum and right anterior corona radiata. Importantly, significant diagnosis-by-age interactions were identified at the bilateral anterior prefrontal cortex, bilateral cuneus, bilateral caudate, and the left cerebellum Crus I for GM and left forceps minor for WM. Finally, age-stratified analyses (model 3) showed distinct patterns in GM and WM volumetric alterations in ASD among subsamples of children, adolescents, and adults.ConclusionsOur findings suggest that the heterogeneous reports on the atypical neuroanatomy of ASD may substantially originate from age variation in the study samples. Age variation and its methodological and biological implications have to be carefully delineated in future studies of the neurobiology of ASD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0022-3) contains supplementary material, which is available to authorized users.

In vitro and animal model data demonstrate that valproic acid (VPA) can ameliorate HIV-associated neurotoxicity. The authors conducted a pilot 10-week placebo-controlled study of VPA 250 mg twice daily in 22 HIV-infected individuals with (n = 16) and without (n = 6) cognitive impairment. VPA was safe and well tolerated, with trends toward improved neuropsychological performance and brain metabolism in the impaired subjects.

Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) to explore its impact in adults with autism spectrum disorder (ASD). Among 25 adults with ASD, 19 (mean age: 20.8 years) completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation) in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT) and the Wisconsin Card Sorting Test (WCST). Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Social Responsiveness Scale (SRS). In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71) while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations.

This pilot study suggests that a higher dosage of zolpidem (> 10 mg/d) is the key risk predictor for CSBs.

Results regarding the effects of methylphenidate and atomoxetine on executive functions were inconsistent and no study has directly compared the efficacy of these two medications in improving executive functions in adults with attention-deficit hyperactivity disorder (ADHD). We conducted an 8-10 wk, open-label, head-to-head, randomized clinical trial involving adults with a clinical diagnosis of ADHD confirmed by psychiatric interview. The two treatment arms were immediate-release methylphenidate (IR-methylphenidate) (n = 31) and atomoxetine once daily (n = 32). Executive functions were assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), including spatial working memory, spatial span, intra-extra dimensional set shifts, rapid visual information processing and Stockings of Cambridge (SOC). In addition to the symptom assessments at baseline (week 0), visit 2 (week 4-5) and visit 3 (week 8–10), they received CANTAB assessments at baseline and visit 3 (60.4 ± 6.3 d). Compared to baseline, adults treated with atomoxetine showed significant improvement in spatial working memory, spatial short-term memory, sustained attention and spatial planning at visit 3; adults treated with IR-methylphenidate showed significant improvement in spatial working memory at visit 3. Comparing the magnitude of improvement in executive functions between these two medications, the effect was generally similar for the two groups, although atomoxetine might have significantly greater efficacy than IR-methylphenidate in terms of improving spatial planning (SOC). Our results provide evidence to support that both IR-methylphenidate and atomoxetine improved various executive functions in adults with ADHD with greater improvement in atomoxetine than IR-methylphenidate in spatial planning.

The posterior superior temporal sulcus is a potential therapeutic target of brain stimulation for autism spectrum disorder. We conducted a 4-week randomized, single-blind parallel sham-controlled trial, followed by additional 4-week open-label intervention to evaluate the feasibility and efficacy regarding intermittent theta burst stimulation over the bilateral posterior superior temporal sulcus in autism spectrum disorder. In total, 78 intellectually able children and adolescents were randomized to the active ( n = 40) and sham groups ( n = 38). During the first 4 weeks, the active group received two-session/week intermittent theta burst stimulation, whereas the sham group received the same number of sham stimulation. After unblinding, both groups received eight-session real stimulation over the additional 4 weeks. In total, 91% participants completed the protocol with mild and transitory side-effects. There was no significant group-by-time interaction for active versus sham group on clinical symptoms and social cognitive performances in the first 4 weeks. The within-group analysis revealed 8 weeks (including a 4-week blind trial and a 4-week open-label intervention) of intermittent theta burst stimulation achieved greater efficacy than 4-week interventions. Participants with higher intelligence, better social cognitive performances, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. Our study demonstrated the feasibility of long-term intermittent theta burst stimulation over the posterior superior temporal sulcus in children and adolescents with autism spectrum disorder. However, the findings from the first 4-week blind trial do not support the therapeutic efficacy of intermittent theta burst stimulation over the posterior superior temporal sulcus on the clinical symptoms and cognitive performance of social impairment, given the current stimulation protocol. The exploratory analyses suggest that the therapeutic efficacy might be moderated by several individual characteristics and more intermittent theta burst stimulation sessions. Lay abstract Intermittent theta burst stimulation is a varied form of repetitive transcranial magnetic non-invasive brain stimulation technique used to treat several neurological and psychiatric disorders. Its feasibility and therapeutic effects on the bilateral posterior superior temporal sulcus in children with autism are unknown. We conducted a single-blind, sham-controlled parallel randomized clinical trial in a hitherto largest sample of intellectually able children with autism ( N = 78). Participants randomized to the active group received two-session/week intermittent theta burst stimulation for continuous 8 weeks. Those in the sham group received two-session/week sham stimulations in the first 4 weeks and then active intervention for the following 4 weeks after unblinding. First, we found that continuous 8-week intermittent theta burst stimulation on the bilateral posterior superior temporal sulcus in children with autism is safe and tolerable. Second, we found that 8-week intermittent theta burst stimulation produced greater therapeutic efficacy, although we did not find any significant effects of 4-week intermittent theta burst stimulation on core symptoms and social cognitive performances in autism. Further analysis revealed that participants with higher intelligence and better social cognitive performance, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. This study identified that the factors contribute to responders and the results suggest that longer courses of non-invasive brain stimulation may be needed to produce therapeutic benefits in autism, with consideration of heterogeneous responses.