Heterogeneity thwarts autism explanatory power: A proposal for endophenotypes

Abstract

Many researchers now believe that autism heterogeneity is likely to include many disorders, but most research is based on samples defined by the DSM-5 Autism Spectrum Disorder (ASD) criteria. However, individuals diagnosed with autism have complex and varied biological causes for their symptoms. Therefore, autism is not a unitary biological entity. And although autism is significantly different from typical development, autism is not a unitary clinical disorder because diagnosed individuals vary in symptom patterns, comorbidities, biomarkers, and gene variants. The DSM-5 ASD criteria were designed to reduce heterogeneity, and there have been many other efforts to reduce autism heterogeneity including using more stringent clinical criteria, dividing autism into low and high functioning groups, creating subgroups, and by studying larger samples. However, to date these efforts have not been successful. Heterogeneity is extensive and remains unexplained, and no autism pathophysiology has been discovered. Most importantly, heterogeneity has hindered the explanatory power of the autism diagnosis to discover drug regimens and effective behavioral treatments. The paper proposes that possible transdiagnostic endophenotypes may reduce autism heterogeneity. Searching for transdiagnostic endophenotypes requires exploring autism symptoms outside of the framework of the DSM-5 autism diagnosis. This paper proposes that researchers relax diagnostic criteria to increase the range of phenotypes to support the search for transdiagnostic endophenotypes. The paper proposes possible candidates for transdiagnostic endophenotypes. These candidates are taken from DSM-5 ASD criteria, from concepts that have resulted from researched theories, and from symptoms that are the result of subtyping. The paper then sketches a possible basis for a future transdiagnostic endophenotypes screening tool that includes symptoms of autism and other neurodevelopmental disorders.