Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study.

BACKGROUND: The current study used eye tracking to investigate attention and recognition memory in Phelan-McDermid syndrome (PMS), a rare genetic disorder characterized by intellectual disability, motor delays, and a high likelihood of comorbid autism spectrum disorder (ASD). Social deficits represent a core feature of ASD, including decreased propensity to orient to or show preference for social stimuli. METHODS: We used a visual paired-comparison task with both social and non-social images, assessing looking behavior to a novel image versus a previously viewed familiar image to characterize social attention and recognition memory in PMS (n = 22), idiopathic ASD (iASD, n = 38), and typically developing (TD) controls (n = 26). The idiopathic ASD cohort was divided into subgroups with intellectual disabilities (ID; developmental quotient < 70) and without (developmental quotient > 70) and the PMS group into those with and without a co-morbid ASD diagnosis. RESULTS: On measures of attention, the PMS group with a comorbid ASD diagnosis spent less time viewing the social images compared to non-social images; the rate of looking back and forth between images was lowest in the iASD with ID group. Furthermore, while all groups demonstrated intact recognition memory when novel non-social stimuli were initially presented (pre-switch), participants with PMS showed no preference during the post-switch memory presentation. In iASD, the group without ID, but not the group with ID, showed a novelty preference for social stimuli. Across indices, individuals with PMS and ASD performed more similarly to PMS without ASD and less similarly to the iASD group. CONCLUSION: These findings demonstrate further evidence of differences in attention and memory for social stimuli in ASD and provide contrasts between iASD and PMS.

Social cognitive skills groups increase medial prefrontal cortex activity in children with autism spectrum disorder.

Few studies have examined the neural mechanisms of change following social skills interventions for children with autism spectrum disorder (ASD). This study examined the neural effects of social cognitive skills groups during functional MRI (fMRI) tasks of irony comprehension and eye gaze processing in school-aged children with ASD. Verbally fluent children (ages 8-11) were randomized to social cognitive skills groups or facilitated play comparison groups. Behavioral assessments and fMRI scans were obtained at baseline and endpoint (12 weeks). During fMRI, children completed two separate tasks to engage social cognition circuitry: comprehension of potentially ironic scenarios (n = 34) and viewing emotionally expressive faces with direct or averted gaze (n = 24). Whole-brain analyses were conducted to examine neural changes following treatment. Regression analyses were also conducted to explore the relationship between neural and behavioral changes. When comparing the two groups directly, the social cognitive skills group showed greater increases in activity in the medial prefrontal cortex (mPFC), implicated in theory of mind, relative to the comparison group for both irony comprehension and gaze processing tasks. Increased mPFC activity during the irony task was associated with improvement in social functioning on the Social Responsiveness Scale across both groups. Findings indicate that social cognitive skills interventions may increase activity in regions associated with social cognition and mentalizing abilities. LAY SUMMARY: Social skills groups are a common intervention for school-aged children with ASD. However, few studies have examined the neural response to social skills groups in school-aged children with ASD. Here, we report on a study evaluating neural outcomes from an empirically supported social cognitive skills training curriculum using fMRI. This study seeks to understand the effects of targeting emotion recognition and theory of mind on the brain circuitry involved in social cognition in verbally fluent children ages 8-11. Results indicate increased neural activity in the mPFC, a region considered to be a central hub of the "social brain," in children randomized to social cognitive skills groups relative to a comparison group that received a high-quality, child-directed play approach. In addition, increased activation in the mPFC during an irony comprehension task was associated with gains in social functioning across both groups from pre- to post-treatment. This is the first fMRI study of social skills treatment outcomes following a randomized trial with an active treatment condition in school-aged children with ASD.

Reduced engagement of visual attention in children with autism spectrum disorder.

LAY ABSTRACT: Limited eye contact and difficulty tracking where others are looking are common in people with autism spectrum disorder. It is unclear, however, whether these are specifically social differences; it is possible that they are a result of broader alterations in engaging and disengaging visual attention. We used eye-tracking technology with children with autism spectrum disorder (n = 35) and typical development (n = 32), showing them both social and nonsocial imaging to test their visual attention. Children with autism spectrum disorder had a significant difference in how long it took them to look from an image in the middle to one on the side, depending on whether the middle image stayed on the screen or flashed off before the one on the side appeared. This difference was present for both social and nonsocial images, and was related to cognitive ability for only the children with autism spectrum disorder. Our findings suggest that children with autism spectrum disorder have differences in general processes of engaging visual attention that are not specifically social in nature, and that these processes may relate to cognitive ability in autism spectrum disorder. Affected processes of visual engagement in autism spectrum disorder may contribute to symptoms like reduced eye contact, but social-specific symptoms of autism spectrum disorder likely do not stem from reduced visual engagement alone.

Brief Report: A Job-Based Social Skills Program (JOBSS) for Adults with Autism Spectrum Disorder: A Pilot Randomized Controlled Trial.

Adults with autism spectrum disorder (ASD) have low employment rates; even those who are employed have low wages and limited hours. This study evaluated the effectiveness of the Job-Based Social Skills (JOBSS) curriculum, a manualized, 15-week, group-delivered intervention for adults with ASD. The intervention aimed to increase social-pragmatic skills necessary to obtain and maintain employment. Twenty-two adults were randomly assigned to either JOBSS intervention or wait-list control groups. Results showed significant improvement in social cognition, as reported by caregivers, among JOBSS group participants compared to wait-list control participants. Forty-five percent of intervention participants gained employment in the six months following participation. This curriculum has potential to improve social skills of adults with ASD, thereby increasing successful employment.

Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations.

Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to SHANK3 haploinsufficiency, but also usually encompassing many other genes. While the number of point mutations identified in SHANK3 has increased in recent years due to large-scale sequencing studies, systematic studies describing the phenotype of individuals harboring such mutations are lacking. Methods: We provide detailed clinical and genetic data on 17 individuals carrying mutations in SHANK3. We also review 60 previously reported patients with pathogenic or likely pathogenic SHANK3 variants, often lacking detailed phenotypic information. Results: SHANK3 mutations in our cohort and in previously reported cases were distributed throughout the protein; the majority were truncating and all were compatible with de novo inheritance. Despite substantial allelic heterogeneity, four variants were recurrent (p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A), suggesting that these are hotspots for de novo mutations. All individuals studied had intellectual disability, and autism spectrum disorder was prevalent (73%). Severe speech deficits were common, but in contrast to individuals with 22q13.3 deletions, the majority developed single words, including 41% with at least phrase speech. Other common findings were consistent with reports among individuals with 22q13.3 deletions, including hypotonia, motor skill deficits, regression, seizures, brain abnormalities, mild dysmorphic features, and feeding and gastrointestinal problems. Conclusions: Haploinsufficiency of SHANK3 resulting from point mutations is sufficient to cause a broad range of features associated with PMS. Our findings expand the molecular and phenotypic spectrum of PMS caused by SHANK3 point mutations and suggest that, in general, speech impairment and motor deficits are more severe in the case of deletions. In contrast, renal abnormalities associated with 22q13.3 deletions do not appear to be related to the loss of SHANK3.

Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder.

Phelan-McDermid syndrome (PMS) is a single-locus cause of developmental delay, autism spectrum disorder, and minimal verbal abilities. There is an urgent need to identify objective outcome measures of expressive language for use in this and other minimally verbal populations. One potential tool is an automated language processor called Language ENvironment Analysis (LENA). LENA was used to obtain over 542 h of audio in 18 children with PMS. LENA performance was adequate in a subset of children with PMS, specifically younger children and those with fewer stereotypic vocalizations. One LENA-derived language measure, Vocalization Ratio, had improved accuracy in this sample and may represent a novel expressive language measure for use in severely affected populations.

A clinician-administered observation and corresponding caregiver interview capturing DSM-5 sensory reactivity symptoms in children with ASD.

BACKGROUND: Sensory reactivity is a new criterion for autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). However, there is no consensus on how to reliably measure sensory reactivity, particularly in minimally verbal individuals. The current study is an initial validation of the Sensory Assessment for Neurodevelopmental Disorders (SAND), a novel clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on DSM-5 criteria for ASD. METHODS: Eighty children between the ages of 2 and 12 participated in this study; 44 children with ASD and 36 typically developing (TD) children. Sensory reactivity symptoms were measured using the SAND and the already validated Short Sensory Profile (SSP). Initial psychometric properties of the SAND were examined including reliability, validity, sensitivity and specificity. RESULTS: Children with ASD showed significantly more sensory reactivity symptoms compared to TD children across sensory domains (visual, tactile, and auditory) and within sensory subtypes (hyperreactivity, hyporeactivity and seeking). The SAND showed strong internal consistency, inter-rater reliability and test-retest reliability, high sensitivity (95.5%) and specificity (91.7%), and strong convergent validity with the SSP. SIGNIFICANCE: The SAND provides a novel method to characterize sensory reactivity symptoms based on DSM-5 criteria for ASD. This is the first known sensory assessment that combines a clinician-administered observation and caregiver interview to optimally capture sensory phenotypes characteristic of individuals with neurodevelopmental disorders. The SAND offers a beneficial new tool for both research and clinical purposes and has the potential to meaningfully enhance gold-standard assessment of ASD. Autism Res 2017, 10: 1133-1140. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Rapid and Objective Assessment of Neural Function in Autism Spectrum Disorder Using Transient Visual Evoked Potentials.

OBJECTIVE: There is a critical need to identify biomarkers and objective outcome measures that can be used to understand underlying neural mechanisms in autism spectrum disorder (ASD). Visual evoked potentials (VEPs) offer a noninvasive technique to evaluate the functional integrity of neural mechanisms, specifically visual pathways, while probing for disease pathophysiology. METHODS: Transient VEPs (tVEPs) were obtained from 96 unmedicated children, including 37 children with ASD, 36 typically developing (TD) children, and 23 unaffected siblings (SIBS). A conventional contrast-reversing checkerboard condition was compared to a novel short-duration condition, which was developed to enable objective data collection from severely affected populations who are often excluded from electroencephalographic (EEG) studies. RESULTS: Children with ASD showed significantly smaller amplitudes compared to TD children at two of the earliest critical VEP components, P60-N75 and N75-P100. SIBS showed intermediate responses relative to ASD and TD groups. There were no group differences in response latency. Frequency band analyses indicated significantly weaker responses for the ASD group in bands encompassing gamma-wave activity. Ninety-two percent of children with ASD were able to complete the short-duration condition compared to 68% for the standard condition. CONCLUSIONS: The current study establishes the utility of a short-duration tVEP test for use in children at varying levels of functioning and describes neural abnormalities in children with idiopathic ASD. Implications for excitatory/inhibitory balance as well as the potential application of VEP for use in clinical trials are discussed.

Erratum to: Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome.

[This corrects the article DOI: 10.1186/s11689-016-9138-9.].

Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS. No controlled neuroimaging studies of PMS have been reported to date. The goal of this study was to examine the neural circuitry supporting the perception of auditory communicative signals in children with PMS as compared to idiopathic ASD (iASD). METHODS: Eleven children with PMS and nine comparison children with iASD were scanned using functional magnetic resonance imaging (fMRI) under light sedation. The fMRI paradigm was a previously validated passive auditory task, which presented communicative (e.g., speech, sounds of agreement, disgust) and non-communicative vocalizations (e.g., sneezing, coughing, yawning). RESULTS: Previous research has shown that the superior temporal gyrus (STG) responds selectively to communicative vocal signals in typically developing children and adults. Here, selective activity for communicative relative to non-communicative vocalizations was detected in the right STG in the PMS group, but not in the iASD group. The PMS group also showed preferential activity for communicative vocalizations in a range of other brain regions associated with social cognition, such as the medial prefrontal cortex (MPFC), insula, and inferior frontal gyrus. Interestingly, better orienting toward social sounds was positively correlated with selective activity in the STG and other "social brain" regions, including the MPFC, in the PMS group. Finally, selective MPFC activity for communicative sounds was associated with receptive language level in the PMS group and expressive language in the iASD group. CONCLUSIONS: Despite shared behavioral features, children with PMS differed from children with iASD in their neural response to communicative vocal sounds and showed relative strengths in this area. Furthermore, the relationship between clinical characteristics and neural selectivity also differed between the two groups, suggesting that shared ASD features may partially reflect different neurofunctional abnormalities due to differing etiologies.

Measuring Sensory Reactivity in Autism Spectrum Disorder: Application and Simplification of a Clinician-Administered Sensory Observation Scale.

Sensory reactivity is a new DSM-5 criterion for autism spectrum disorder (ASD). The current study aims to validate a clinician-administered sensory observation in ASD, the Sensory Processing Scale Assessment (SPS). The SPS and the Short Sensory Profile (SSP) parent-report were used to measure sensory reactivity in children with ASD (n = 35) and typically developing children (n = 27). Sixty-five percent of children with ASD displayed sensory reactivity symptoms on the SPS and 81.1 % on the SSP. SPS scores significantly predicted SSP scores. We next identified the five SPS tasks that best differentiated groups. Our results indicate that a combination of parent-report and at least the five most differentiating observational tasks may be most sensitive in identifying the presence of sensory reactivity issues.

Erratum: A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome.

[This corrects the article DOI: 10.1186/2040-2392-5-54.].

Randomized comparative trial of a social cognitive skills group for children with autism spectrum disorder.

OBJECTIVE: This study evaluated the efficacy of a targeted social skills training group in school-aged children with autism spectrum disorder (ASD). The intervention, Seaver-NETT (Nonverbal communication, Emotion recognition, and Theory of mind Training), is a 12-session cognitive-behavioral intervention (CBI) for verbal, school-aged children targeting ASD-specific social behavioral impairments. METHOD: Sixty-nine children with ASD, 8 to 11 years of age, with verbal IQs greater than 70, participated in a randomized comparative trial to examine the efficacy of NETT relative to a facilitated play group. Treatment outcomes included caregiver reports of social behavior and neuropsychological assessments of social cognition conducted by blinded raters. Outcomes were collected at baseline, endpoint, and 3 months posttreatment. RESULTS: Significant improvements were found on social behavior outcomes such as nonverbal communication, empathic responding, and social relations in the NETT condition relative to the active control at endpoint. Verbal IQ moderated the interaction effect on social behavior, with higher verbal IQ associated with improvements in the CBI condition. No significant improvements were found on social cognitive outcomes. No significant group differences were found at 3-month follow-up conducted with approximately half the sample (n = 34). CONCLUSION: These data indicate that targeted CBI social skills groups such as NETT improve social communication deficits in verbal, school-aged children with ASD. The moderating effects of high verbal IQ suggest a need to consider participant and treatment characteristics associated with outcomes in future studies. Clinical trial registration information-Neural and Behavioral Outcomes of Social Skills Groups in Children With Autism Spectrum Disorder; https://clinicaltrials.gov; NCT01190917.

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.

Metabolic mapping of deep brain structures and associations with symptomatology in autism spectrum disorders.

Structural neuroimaging studies in autism report atypical volume in deep brain structures which are related to symptomatology. Little is known about metabolic changes in these regions, and how they vary with age and sex, and/or relate to clinical behaviors. Using magnetic resonance spectroscopy we measured N-acetylaspartate, choline, creatine, myoinositol and glutamate in the caudate, putamen, and thalamus of 20 children with autism and 16 typically developing controls (7-18 years). Relative to controls, individuals with autism had elevated glutamate/creatine in the putamen. In addition, both groups showed age-related increases in glutamate in this region. Boys, relative to girls had increased choline/creatine in the thalamus. Lastly, there were correlations between glutamate, choline, and myoinositol in all three regions, and behavioral scores in the ASD group. These findings suggest changes in deep gray matter neurochemistry, which are sensitive to diagnosis, age and sex, and are associated with behavioral differences.

A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome.

BACKGROUND: Autism spectrum disorder (ASD) is now understood to have multiple genetic risk genes and one example is SHANK3. SHANK3 deletions and mutations disrupt synaptic function and result in Phelan-McDermid syndrome (PMS), which causes a monogenic form of ASD with a frequency of at least 0.5% of ASD cases. Recent evidence from preclinical studies with mouse and human neuronal models of SHANK3 deficiency suggest that insulin-like growth factor-1 (IGF-1) can reverse synaptic plasticity and motor learning deficits. The objective of this study was to pilot IGF-1 treatment in children with PMS to evaluate safety, tolerability, and efficacy for core deficits of ASD, including social impairment and restricted and repetitive behaviors. METHODS: Nine children with PMS aged 5 to 15 were enrolled in a placebo-controlled, double-blind, crossover design study, with 3 months of treatment with IGF-1 and 3 months of placebo in random order, separated by a 4-week wash-out period. RESULTS: Compared to the placebo phase, the IGF-1 phase was associated with significant improvement in both social impairment and restrictive behaviors, as measured by the Aberrant Behavior Checklist and the Repetitive Behavior Scale, respectively. IGF-1 was found to be well tolerated and there were no serious adverse events in any participants. CONCLUSIONS: This study establishes the feasibility of IGF-1 treatment in PMS and contributes pilot data from the first controlled treatment trial in the syndrome. Results also provide proof of concept to advance knowledge about developing targeted treatments for additional causes of ASD associated with impaired synaptic development and function.

Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring.

Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes. One example is SHANK3 on the terminal end of chromosome 22q. Loss of one functional copy of SHANK3 results in 22q13 deletion syndrome or Phelan-McDermid syndrome (PMS) and causes a monogenic form of ASD and/or ID with a frequency of 0.5% to 2% of cases. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. With chromosomal microarray analyses now a standard of care in the assessment of ASD and developmental delay, and with the emergence of whole exome and whole genome sequencing in this context, identification of PMS in routine clinical settings will increase significantly. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. Evaluations must include a thorough history and physical and dysmorphology examination. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Endocrine, renal, cardiac, and gastrointestinal problems all require assessment and monitoring in addition to the risk of recurring infections, dental and vision problems, and lymphedema. Finally, all patients should have cognitive, behavioral, and ASD evaluations. The objective of this paper is to address this gap in the literature and establish recommendations to assess the medical, genetic, and neurological features of PMS.

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency.

BACKGROUND: 22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is a neurodevelopmental disorder characterized by intellectual disability, hypotonia, delayed or absent speech, and autistic features. SHANK3 has been identified as the critical gene in the neurological and behavioral aspects of this syndrome. The phenotype of SHANK3 deficiency has been described primarily from case studies, with limited evaluation of behavioral and cognitive deficits. The present study used a prospective design and inter-disciplinary clinical evaluations to assess patients with SHANK3 deficiency, with the goal of providing a comprehensive picture of the medical and behavioral profile of the syndrome. METHODS: A serially ascertained sample of patients with SHANK3 deficiency (n = 32) was evaluated by a team of child psychiatrists, neurologists, clinical geneticists, molecular geneticists and psychologists. Patients were evaluated for autism spectrum disorder using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-G. RESULTS: Thirty participants with 22q13.3 deletions ranging in size from 101 kb to 8.45 Mb and two participants with de novo SHANK3 mutations were included. The sample was characterized by high rates of autism spectrum disorder: 27 (84%) met criteria for autism spectrum disorder and 24 (75%) for autistic disorder. Most patients (77%) exhibited severe to profound intellectual disability and only five (19%) used some words spontaneously to communicate. Dysmorphic features, hypotonia, gait disturbance, recurring upper respiratory tract infections, gastroesophageal reflux and seizures were also common. Analysis of genotype-phenotype correlations indicated that larger deletions were associated with increased levels of dysmorphic features, medical comorbidities and social communication impairments related to autism. Analyses of individuals with small deletions or point mutations identified features related to SHANK3 haploinsufficiency, including ASD, seizures and abnormal EEG, hypotonia, sleep disturbances, abnormal brain MRI, gastroesophageal reflux, and certain dysmorphic features. CONCLUSIONS: This study supports findings from previous research on the severity of intellectual, motor, and speech impairments seen in SHANK3 deficiency, and highlights the prominence of autism spectrum disorder in the syndrome. Limitations of existing evaluation tools are discussed, along with the need for natural history studies to inform clinical monitoring and treatment development in SHANK3 deficiency.

Effects of age and symptomatology on cortical thickness in autism spectrum disorders.

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours.

The effect of diagnosis, age, and symptom severity on cortical surface area in the cingulate cortex and insula in autism spectrum disorders.

Functional activity in the anterior cingulate cortex and insula has been reported to be abnormal during social tasks in autism spectrum disorders. However, few studies have examined surface morphometry in these regions and how this may be related to autism spectrum disorder symptomatology. In this study, 27 individuals with autism spectrum disorders and 25 controls between the ages of 7 to 39 years underwent structural magnetic resonance imaging. Our primary analysis examined differences in surface area in the cingulate and insula, between individuals with and without autism spectrum disorders, as well as age-related changes and associations with social impairments. Surface area in the right cingulate was significantly different between groups and decreased more rapidly with age in autism spectrum disorder participants. In addition, greater surface area in the insula and isthmus was associated with poorer social behaviors. Results suggest atypical surface morphometry in brain regions involved in social function, which appeared to be related to poorer social ability scores.