The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Recent estimates suggest that over 30% of children with autism spectrum disorders (ASD) meet diagnostic criteria for attention deficit/hyperactivity disorder (ADHD), and another 20% of children with ASD exhibit subthreshold clinical ADHD symptoms. Presence of ADHD symptoms in the context of ASD could have a variety of effects on cognition, autistic traits, and adaptive/ maladaptive behaviors including: exacerbating core ASD impairments; adding unique impairments specific to ADHD; producing new problems unreported in ASD or ADHD; having no clear impact; or producing some combination of these scenarios. Children with ASD and comorbid ADHD symptoms (ASD+ADHD; n=21), children with ASD without ADHD (ASD; n=28), and a typically developing control group (n=21) were included in the study; all groups were matched on age, gender-ratio, IQ, and socioeconomic status. Data were collected on verbal and spatial working memory, response inhibition, global executive control, autistic traits, adaptive functioning, and maladaptive behavior problems. In this sample, the presence of ADHD symptoms in ASD exacerbated impairments in executive control and adaptive behavior and resulted in higher autistic trait, and externalizing behavior ratings. ADHD symptoms were also associated with greater impairments on a lab measure of verbal working memory. These findings suggest that children with ASD+ADHD symptoms present with exacerbated impairments in some but not all domains of functioning relative to children with ASD, most notably in adaptive behavior and working memory. Therefore, ADHD may moderate the expression of components of the ASD cognitive and behavioral phenotype, but ASD+ADHD may not represent an etiologically distinct phenotype from ASD alone.Autism spectrum disorders (ASD) and attention deficit hyperactivity disorders (ADHD) are diagnosed based upon behavioral symptoms (APA, 2000). ASD is characterized by impairments in social functioning, communication, and restricted, repetitive behaviors/ interests, while ADHD is characterized by inattention and hyperactivity/impulsivity. Address Correspondence to: Benjamin E. Yerys, PhD, Children's Research Institute -Neuroscience, Children's National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010, Phone: (202) Fax: (301) 765-5497. 2 When spatial working memory data is combined for the ASD and ASD+ADHD groups and then compared to the TYP group we find a significant difference in total between errors, t(56) =2.81, p<0.05, Cohen's d=0.61).There are no conflicts of interest, financial or otherwise, for the remaining authors involved directly or indirectly with this manuscript. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAlthough the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Text Revision (DSM-IV-TR; APA, 2000) precludes a co-morbid diagnosis of ASD and ADHD, a recent study examining co-morbidity revealed that over 30% of children with highfunctioning ASD met diagnostic criteria for ADHD and a...

FMRI in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with Epilepsy, Attention Deficit/ Hyperactivity Disorder (ADHD), Autism Spectrum Disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (Epilepsy: 80%; ADHD (off methylphenidate): 77%; ADHD (on methylphenidate): 81%; ASD: 70%; TYP: 87%). Ten to 18-year-olds had a significantly greater scan success rate than 4-6-year-olds; adolescents (13-18-year-olds) demonstrated greater scan success rates than 7-9-year-olds. Success rate for completing an entire battery of experimental runs (n=2-6), varied between 50-59% for patient populations and 69% for TYP (79% when excluding 4-6-year-olds). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20-30% more children should be recruited in these patient groups, but only 10-20% for TYP for research studies. Studies with 4-6-year-olds may require 20-40% additional participants; studies with 10-18-year-olds may require 10-15% additional participants.Functional magnetic resonance imaging (fMRI) is an established tool in the study of brain function in children with developmental disorders, acquired disorders, and typical development (TYP) and has a clinical application in pre-surgical planning for children with Epilepsy (Medina et al., 2007). Unlike structural MRI where participants are required to lie still (and may do so while sleeping), fMRI requires awake and cooperative participants which precludes the use of sedation. There is a paucity of data examining the success rate of scanning children in fMRI paradigms.Address Correspondence: Benjamin E. Yerys, Children's National Medical Center, Children's Research Institute -Neuroscience, 111 Michigan Ave, NW, Washington, DC 20010, byerys@cnmc.org, Phone: 301-738-8940. NIH Public Access Author ManuscriptHum Brain Mapp. Author manuscript; available in PMC 2010 October 1. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptOne study has examined scan success rate in over 200 TYP children between 5-to 18-years of age (Byars et al., 2002). This study defined scan success as children completing at least one of four fMRI tasks and an anatomical reference scan. Children between the ages of five and six had a success rate of 47%; children between the ages of seven and nine had a success rate of 76%; and children above the age of ten had a success rate of 96%. It is unk...

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IMPORTANCE Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.OBJECTIVE To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia (SCZ). DESIGN, SETTING, AND PARTICIPANTSProfiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The number of cases and controls in each of the 6 disorders were as follows:

Functional magnetic resonance imaging was used to examine functional anatomy of attention to social (eye gaze) and nonsocial (arrow) communicative stimuli in late childhood and in a disorder defined by atypical processing of social stimuli, Autism Spectrum Disorders (ASD). Children responded to a target word ('LEFT'/'RIGHT') in the context of a distracting arrow or averted gaze pointing in a direction that was congruent, incongruent, or neutral (bar without arrowheads, central gaze) relative to the target word. Despite being irrelevant to the target task, both arrow and averted gaze facilitated responses (Congruent vs. Neutral trials) to the same extent in the two groups and led to interference (Incongruent vs. Congruent trials), which was greater from arrows in ASD than control children. In the brain, interaction between group and distracter-domain was observed in frontal-temporal regions during facilitation and frontal-striatal regions during interference. During facilitation, regions associated with attention to gaze in control children (left superior temporal sulcus, premotor) were associated with attention to arrows in ASD children; gaze was associated with medial temporal involvement in ASD children. During interference, regions associated with arrows in control children (anterior cingulate, right caudate) were activated in response to gaze in ASD children; further, left dorsolateral prefrontal cortex, a region not observed in control children, was activated during gaze-interference in ASD children. Thus, functional anatomy was atypical in ASD children during spontaneous processing of social and nonsocial communicative cues.

Background Polymorphism of the dopamine transporter genotype (DAT1) confers a small but significant susceptibility to Attention Deficit Hyperactivity Disorder (ADHD). We examined whether the volume of the head of caudate, a striatal structure with high DAT expression that is important for inhibitory function, differs by DAT1 in a children diagnosed with the disorder relative to age and IQ matched controls. Method Volume of the head of caudate was delineated in the right and left hemisphere and compared between 7–13 year old children with and without ADHD (Combined type) who were carriers of two (10/10) or one (9/10) copy of the 10-repeat DAT1 allele. Results Caudate volumes were overall smaller 10/10 than 9/10 children, particularly in the left than right hemisphere. While DAT1 effects did not vary by ADHD diagnosis, overall caudate volumes were smaller in ADHD relative to control children. Conclusions Altered caudate development associated with 10-repeat homozygosity of DAT1 may contribute susceptibility to ADHD.