Wouter De la Marche

What’s new in autism?

This review on autism spectrum disorder (ASD) focusses on recent insights in the clinical picture, such as continuity of the phenotype and the concept of broader phenotype, on epidemiology and on clinical issues relevant to physicians, including new methods for early screening and diagnosis, psychiatric and somatic co-morbidity, and the expansion of so-called complementary and alternative treatments. ASD is a disorder with mainly genetic causes and recent insights show that a variety of genetic mechanisms may be involved, i.e. single gene disorders, copy number variations and polygenic mechanisms. Technological advances in genetics have lead to a number of promising findings, which, together with other lines of fundamental research, suggest that ASD may be a disorder of connectivity in the brain, at least in a subgroup of patients. It is possible that part of the genetic load in autism actually reflects gene–environment interaction, but there is no evidence for purely environmental causes in a substantial number of cases. Clinical research suggests that ASD may be a multi-system disorder in at least a subgroup of subjects, affecting the gastro-intestinal (GI) tract, the immune system and perhaps other systems. Behavioural treatments remain the cornerstone of management, and are mainly aimed at stimulation of the domains of impaired development and reducing secondary behaviours. These treatments are constantly being refined, but the main progress in this area may be the increase of research on effectiveness.

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

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.

Measuring quantitative autism traits in families: informant effect or intergenerational transmission?

Autism spectrum disorders (ASD) have a high degree of heritability, but there is still much debate about specific causal genes and pathways. To gain insight into patterns of transmission, research has focused on the relatedness of quantitative autism traits (QAT) between family members, mostly using questionnaires. Yet, different kinds of bias may influence research results. In this paper, we focus on possible informant effects and, taking these into account, on possible intergenerational transmission of QAT. This study used multiple informant data retrieved via the Social Responsiveness Scale from 170 families with at least one member with ASD. Using intraclass correlations (ICCs) and mixed model analyses, we investigated inter-informant agreement and differences between parent and teacher reports on children and between self- and other-reports on adults. Using structural equation modelling (SEM), we investigated the relatedness of QAT between family members in ASD families. Parent–teacher agreement about social responsiveness was poor, especially for children with ASD, though agreement between parents was moderate to strong for affected and unaffected children. Agreement between self- and other-report in adult men was good, but only moderate in women. Agreement did not differ between adults with and without ASD. While accounting for informant effects, our SEM results corroborated the assortative mating theory and the intergenerational transmission of QAT from both fathers and mothers to their offspring.