Facilitating Autism Research

Abstract

Early autism research focused on behavior and cognition. In recent decades, the pace of research has accelerated, and advances in imaging and genetics have allowed the accumulation of biological data. Nevertheless, a coherent picture of the syndrome at either phenotypic or biological level has not emerged. We see two fundamental obstacles to progress in basic understanding of autism. First, the two defining features (impairment in social interactions and communication, and restricted, repetitive behaviors and interests) are historically seen as integrally related. Others hold that these two major traits are fractionable and must be studied independently, casting doubt on autism as a coherent syndrome. Second, despite much recent research on brain structure and function, environmental factors, and genetics/genomics, findings on the biological level have not generally aligned well with those on the phenotypic level. In the first two sections, we explore these challenges, and in the third section, we review approaches that may facilitate progress, such as (1) including in studies all individuals defined by social impairment without regard to repetitive behaviors, (2) forming narrowly defined subtypes by thorough characterization on specific features, both diagnostic and non-diagnostic, (3) focusing on characteristics that may be relatively robust to environmental influence, (4) studying children as early as possible, minimizing environmental influence, and including longitudinal course as an important part of the phenotype, (5) subtyping by environmental risk factors, (6) distinguishing between what participants can do and what they typically do, and (7) aggregating large data sets across sites. (JINS, 2017, 23, 903-915)

The contribution of environmental exposure to the etiology of autism spectrum disorder

“…Stratifying ASD on the basis of factors other than solely intellect, generating more homogenous groups, would still likely support more conclusive findings in relation to the etiology of autism. However, despite effort to subtype ASD and look at environmental and genetic risk factors within subtypes including sex, comorbidities, verbal abilities, neurocognitive and biological endophenotypes, these attempts have thus far not been very fruitful [265]. Nevertheless, there are still multiple options for stratification to be explored.…”

Autism Heterogeneity in a Densely Sampled U.S. Population: Results From the First 1,000 Participants in the RI‐CART Study

“…Despite the clear delineation of these core diagnostic features, ASD often manifests in a manner that can affect nearly all medical and functional domains, including emotional, behavioral, developmental, neurological, medical, and physical domains [Bishop-Fitzpatrick et al, 2018;Joshi et al, 2014;Lord et al, 2000;Lord et al, 2018;Maski, Jeste, & Spence, 2011;McElhanon, McCracken, Karpen, & Sharp, 2014]. While diagnostic classifications can be made with a high level of reliability, the significant heterogeneity of ASD manifestations across multiple levels of analysis (e.g., genetic, neural, behavioral, cognitive) has created a notable degree of variability in well-designed research studies [Fein & Helt, 2017;Gillberg & Fernell, 2014;Rutter, 2014].…”

“…Namely, disadvantaged individuals are underrepresented in ASD research and, more generally, in all clinical research. A combination methodology that can appropriately characterize the participant presentation within a large, well‐represented, population‐based sample may yield a more optimal ASD research sample, although practical issues such as feasibility and funding are ongoing barriers [Fein & Helt, ].…”

Autism Pathogenesis: The Superior Colliculus

“…Non-defined genetic causes represent the most prevalent etiology of ASD and several hundred of genetic markers have been proposed (Willsey et al, 2013). This complexity is increased by prenatal and postnatal genes-environment interactions (Fein and Helt, 2017). For that reason, this line of research could be useful to recognize subtypes of autisms but unfruitful to explain the presence of the cluster of symptoms in the entire spectrum including children with non-genetic etiologies.…”