Ilse Noens

Is There a Common Neuroanatomical Substrate of Language Deficit between Autism Spectrum Disorder and Specific Language Impairment

Discussion of an overlap between specific language impairment (SLI) and autism spectrum disorder (ASD) is on going. The most intriguing overlap between both phenotypes is the similarity in the observed language deficits described in SLI and a subgroup of ASD with co-occurring linguistic impairment, ASD-LI. Examining whether a similar neuroanatomical substrate underlies this phenotypical linguistic overlap, we studied the white matter microstructural properties of the superior longitudinal fascicle (SLF) of 19 ASD-LI adolescents (mean age 13.8 ± 1.6 years) and 21 age-matched controls and compared them with 13 SLI children (mean age 10.1 ± 0.4 years) and 12 age-matched controls. A linguistic profile assessment and a diffusion tensor imaging analysis of the SLF were performed. Linguistic testing revealed a mixed receptive-expressive disorder profile in both groups, confirming their overlap at phenotypical level. At neuroanatomical level, no significant differences in mean SLF fractional anisotropy (FA) and mean SLF apparent diffusion coefficient values between ASD-LI participants and controls were seen. By contrast, the mean SLF FA was significantly reduced in the SLI children as compared with their controls. The observation of structural SLF disturbances in SLI but not in ASD-LI suggests the existence of a different neuroanatomical substrate for the language deficits in both disorders.

Making Sense in a Fragmentary World Communication in People with Autism and Learning Disability

The communicative capabilities of people with autism are impaired and limited in significant ways. The problems are characterized by a lack of intentionality and symbol formation, which indicates that the deviant development of communication in autism is associated with a specific cognitive style. The central coherence theory can offer insight into the specific communication problems of people with autism, since a weaker drive for central coherence leads to problems in sense-making and, consequently, in communication. In the case of the comorbidity of autism and learning disability, the communication problems are aggravated. The crucial point is the determination of the level of sense-making, taking this comorbidity into account. Assessment and intervention have to be tuned to individual needs, in order to increase the communicative competence of people with autism and learning disability.

Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernickes and Brocas areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition. While considerable work has focused on cognitive functioning, several research groups also observed difficulties in social functioning as a prominent feature of NF1. These problems and the possible link between NF1 and Autism Spectrum Disorder (ASD) have become increasingly important in recent NF1 literature. The aim of the current study was to assess ASD characteristics in a hospital‐based NF1 pediatric population (n = 82) using the standardized Children Social Behavior Questionnaire (CSBQ) and Social Responsiveness Scale (SRS) to account for the prevalence, severity, and nature of social problems. In a parallel study, comprehensive ASD assessment was performed in a subgroup of NF1 children with a strong suspicion of ASD (n = 31). Results indicate that NF1 children have more social problems than typical controls, more frequently reported above 8 years. The SRS shows that 63% is at risk of ASD symptoms. According to item analyses, most problems were observed on items measuring orientation in, understanding of and being tuned onto a social situation (CSBQ) and social cognition and communication (SRS). In the parallel study, 27 NF1 children were diagnosed with ASD. These children have a distinct phenotype compared to a heterogeneous ASD group, with pronounced social–communicative impairments and fewer restrictive/repetitive behaviors. This study provides a better understanding of social problems in NF1 and the phenotypical overlap with ASD symptomatology. Despite their willingness to engage with others, NF1 children with or without ASD encounter various difficulties in their social–communicative life.

Diagnosing Autism Spectrum Disorder: who will get a DSM‐5 diagnosis?

Background Introduction of proposed criteria for DSM-5 Autism Spectrum Disorder (ASD) has raised concerns that some individuals currently meeting diagnostic criteria for Pervasive Developmental Disorder (PDD; DSM-IV-TR/ICD-10) will not qualify for a diagnosis under the proposed changes. To date, reports of sensitivity and specificity of the new criteria have been inconsistent across studies. No study has yet considered how changes at the ‘sub domain’ level might affect overall sensitivity and specificity, and few have included individuals of different ages and ability levels. Methods A set of DSM-5 ASD algorithms were developed using items from the Diagnostic Interview for Social and Communication Disorders (DISCO). The number of items required for each DSM-5 subdomain was defined either according to criteria specified by DSM-5 (Initial Algorithm), a statistical approach (Youden J Algorithm), or to minimise the number of false positives while maximising sensitivity (Modified Algorithm). The algorithms were designed, tested and compared in two independent samples (Sample 1, N = 82; Sample 2, N = 115), while sensitivity was assessed across age and ability levels in an additional dataset of individuals with an ICD-10 PDD diagnosis (Sample 3, N = 190). Results Sensitivity was highest in the Initial Algorithm, which had the poorest specificity. Although Youden J had excellent specificity, sensitivity was significantly lower than in the Modified Algorithm, which had both good sensitivity and specificity. Relaxing the domain A rules improved sensitivity of the Youden J Algorithm, but it remained less sensitive than the Modified Algorithm. Moreover, this was the only algorithm with variable sensitivity across age. All versions of the algorithm performed well across ability level. Conclusions This study demonstrates that good levels of both sensitivity and specificity can be achieved for a diagnostic algorithm adhering to the DSM-5 criteria that is suitable across age and ability level.

Vineland Screener 0–12 years research version (NL). Constructing a screening instrument to assess adaptive behaviour

In Western countries the need to assess the adaptive behaviour of a wide range of individuals within the framework of research and policy‐making has increased in recent years. To meet this need a screener version of the Vineland Adaptive Behaviour Scales (VABS) was developed in the Netherlands. This screener is a questionnaire to be filled out by primary care‐givers. Using a limited number of items the instrument covers the four domains of adaptive behaviour portrayed in the original Expanded Version of the VABS.

Intentional communication in nonverbal and verbal low-functioning children with autism.

UNLABELLED In this study we characterized profiles of communicative functions and forms of children with autism and intellectual disability (n=26), as compared to typically developing children (n=26) with a comparable nonverbal mental age (2-5 years). Videotapes of the Communication and Symbolic Behavior Scales - Developmental Profile were analyzed using a standardized observation scheme in which three main functions were distinguished: behavior regulation, social interaction, and joint attention. Different forms of communication were also investigated: gestures, vocalizations/verbalizations, and eye gaze. Results indicated that in typically developing children the proportion of communication for the purpose of joint attention was much higher than for behavior regulation, whereas in children with autism the opposite pattern was seen. Low-functioning nonverbal children with autism mainly communicated for behavior regulation and not or only rarely for declarative purposes. Generally, this subgroup used the least complex forms to communicate. Low-functioning verbal children with autism differed from typically developing children only in the rate, not in the proportion of communication for specific functions. Combinations of three different communicative forms were used by verbal children with autism less frequently than by typically developing children. LEARNING OUTCOMES After reading this paper, readers should be able to: (1) describe early development of communicative functions, (2) explain differences in communication profiles with respect to form and function between verbal and nonverbal low-functioning children with autism and typically developing children matched on nonverbal mental age and (3) discuss clinical implications of the findings for communication interventions in verbal and nonverbal low-functioning children with autism.

Narrowing the critical deletion region for autism spectrum disorders on 16p11.2.

Narrowing the Critical Deletion Region for Autism Spectrum Disorders on 16p11.2 An Crepel, Jean Steyaert, Wouter De la Marche, Veerle De Wolf, Jean-Pierre Fryns, Ilse Noens, Koen Devriendt, and Hilde Peeters* Center for Human Genetics, Clinical Genetics, K.U.Leuven, Leuven, Belgium Department of Child and Adolescent Psychiatry, UPC-K.U.Leuven, Leuven, Belgium Department of Clinical Genetics, Academic Hospital Maastricht, and Research Institute Growth & Development (GROW), Maastricht University, Maastricht, The Netherlands Center for Parenting, Child Welfare and Disabilities, Department of Educational Sciences, University of Leuven, Leuven, Belgium Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts

Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity

Impaired executive functioning (EF) has been proposed to underlie symptoms of autism spectrum disorders (ASD). However, insight in the EF profile of ASD individuals is hampered due to task impurity and inconsistent findings. To elucidate these inconsistencies, we investigated the influence of task and sample characteristics on EF in ASD, with an extended test battery designed to reduce task impurity. Additionally, we studied the relation between EF and ASD symptoms. EF (inhibition, cognitive flexibility, generativity, working memory and planning) was measured in open-ended versus structured assessment situations, while controlling for possible confounding EF and non-EF variables. The performance of 50 individuals with ASD was compared with that of 50 age, gender and IQ matched typically developing (TD) individuals. The effects of group (ASD versus TD), age (children versus adolescents) and gender were examined, as well as the correlation between age, IQ, ASD symptoms and EF. Individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in open-ended compared to structured settings. Group differences did not depend on gender and only occasionally on participants’ age. This suggests that inconsistencies between studies largely result from differences in task characteristics and less from differences in the investigated sample features. However, age and IQ strongly correlated with EF, indicating that group differences in these factors should be controlled for when studying EF. Finally, EF correlated with both social and non-social ASD symptoms, but further research is needed to clarify the nature of this relationship.

Quantitative autism traits in first degree relatives: evidence for the broader autism phenotype in fathers, but not in mothers and siblings:

Autism spectrum disorder (ASD) symptoms are present in unaffected relatives and individuals from the general population. Results are inconclusive, however, on whether unaffected relatives have higher levels of quantitative autism traits (QAT) or not. This might be due to differences in research populations, because behavioral data and molecular genetic research suggest that the genetic etiology of ASD is different in multiplex and simplex families. We compared 117 unaffected siblings and 276 parents of at least one child with ASD with 280 children and 595 adults from the general population on the presence of QAT using the Social Responsiveness Scale (SRS). Mean SRS scores for siblings, control children, parents and control adults were 25.4, 26.6, 33.7 and 32.9. Fathers of children with ASD showed significantly higher levels of QAT than controls, but siblings and mothers did not. We could not detect a statistically significant difference in SRS scores between relatives from simplex and multiplex families. These results do not support the theory of differential (genetic) etiology in multiplex and simplex families and suggest that a carried genetic risk is generally not expressed phenotypically in most relatives, except in fathers.