EU-AIMS -  an overview

Speakers: Professor Declan Murphy (Institute of Psychiatry, King’s College London) and Dr Will Spooren (Roche)

Professor Declan Murphy and Dr Will Spooren give an introductory talk about EU-AIMS. They present a general overview of EU-AIMS, its aims and how these aims are being accomplished.

Biomarkers in EU-AIMS

Why do we need stratification biomarkers for autism spectrum disorder? An overview of the EU-AIMS Longitudinal European Autism Project

Speaker: Dr. Eva Loth (Institute of Psychiatry, King’s College London)

Over the past years, researchers and clinicians have begun to recognize the enormous diversity between individuals with autism spectrum disorder (ASD) as a fundamental feature of this condition. For example, some children with ASD grow into independent adults while others remain very severely impaired throughout life. Some children with ASD also develop ADHD, depression or anxiety while others do not. Currently, we do not know what underpins these different symptom profiles and developmental trajectories, but we assume that different (genetic and environmental) factors may cause different forms of autism. We also recognize that different people with ASD not only want and need different types of treatment but also that many treatments may only work effectively for certain individuals. “Precision medicine” is a new approach that aims to match specific treatments to specific individuals that are most likely to benefit from them through use of stratification biomarkers. These are tests that help us to ascertain what form of autism a person may have based on a better understanding of his or her biological profile. So far, we do not have any validated biomarkers for ASD – primarily because most previous studies treated people with ASD as a uniform group and/ or because many studies were too small to look at sub-groups.

In this talk, Dr. Eva Loth (responsible for the Project Science Coordination and Deputy Lead Clinical Research in EU-AIMS) gives an overview of the EU-AIMS Longitudinal European Autism Project (LEAP).  LEAP is currently the worldwide largest study that aims to identify markers or tests that help us to divide ASD into different (biological) subgroups. The study is concurrently carried out in seven European study centres and includes over 800 individuals and their families. Each participant is comprehensively characterised in terms of his or her autism symptoms, associated mental health symptoms, functional outcomes, neurocognitive (psychological, emotional) profile, brain structure and function, biochemical markers and genomics.

Dr. Loth describes the study design, procedures, and the clinical characterisation of the sample. She outlines some approaches to identify subgroups using a person’s strengths and weaknesses across different cognitive tests as an example. Dr. Loth also describes the procedures intended to move the field forward by increasing transparency, robustness and reproducibility of the analyses, which is key for a biomarker to be used eventually in clinical practice.

Sex/Gender Differences and Autism

Why are sex and gender important for understanding autism?

Speaker: Dr. Meng-Chuan Lai (University of Toronto)

Autism has long been perceived as a male-predominant condition. Studies from clinical samples typically find a male:female prevalence ratio of 4-5:1, whereas population-based studies with active case ascertainment find a ratio closer to 3:1. These sex/gender ratios suggest sex/gender-related liability to developing autism, but the difference in clinical versus population estimates suggest some degree of ascertainment and diagnostic bias. Overall this may have resulted in male-biased identification and understanding of autism to date. Understanding autism in the light of sex and gender informs their moderating roles in both the presentation and emergence of this condition.

First, understanding how sex and gender moderate the presentation of behavioural characteristics of autism will inform why males are more likely to be identified. Females with autism tend to be under-recognized owing to higher likelihood of subtler and partially different behavioral presentation, and possible biases on the interpretation of their behaviours by the source of referral or the clinician.

Second, clarifying how variables related to sex and gender contribute to the male-predominance of prevalence will inform the diverse aetiologies and developmental mechanisms of autism. This may involve particularly the convergence of developmental pathways between the emergence of autism characteristics, typical sexual differentiation and gender socialization.

The optimization of supports for girls and women with autism is best based on the understanding of their needs and characteristics considering the moderating roles of sex and gender, targeting at resilience and person-environment fit, and taking into account the influences of gendered social-cultural contexts. This involves not only skill-building and graded exposure for the individual, but more importantly, the adjustment of the social and physical environments.