Specific Medical Conditions Are Associated with Unique Behavioral Profiles in Autism Spectrum Disorders
Autism spectrum disorder (ASD) is a heterogeneous group of disorders which occurs with numerous medical conditions. In previous research, subtyping in ASD has been based mostly on cognitive ability and ASD symptom severity. Several medical conditions have frequently been described as co-occurring with ASD. Research so far has not addressed the question of whether unique medical conditions occur in specific ASD subtypes. Medical phenotypes can potentially be used as biological variables to define specific endophenotypes in ASD.
The aim of the current study was to investigate whether specific medical conditions in ASD, including macrocephaly, microcephaly, developmental regression, food selectivity, and sleep problems are associated with unique behavioral profiles.
The study population included 1,224 participants, 1043 males and 181 females (M:F ratio=5.8:1) with a mean age of 49.9m (SD=29.4) diagnosed with ASD. All the participants underwent comprehensive assessments, including medical history and neurological examination, cognitive and adaptive behavior evaluations, and ASD diagnostic tests. The behavioral profile was composed of cognitive ability, adaptive skills, and autism severity using the relevant standardized scores and was examined in each of the aforementioned medical conditions.
Groups with and without the defined medical conditions were compared on the behavioral measures. Developmental regression was present in 19% of the population and showed a more severe clinical presentation, with lower cognitive abilities, more severe ASD symptoms, and more impaired adaptive functioning. Microcephaly was observed in 6.3% of the population and was characterized by a lower cognitive ability and more impaired adaptive functioning in comparison to the normative head circumference (HC) group. Severe food selectivity was found in 9.8% and severe sleep problems in 5.1% of the ASD population. The food selectivity and sleep problem subgroups both showed more impaired adaptive skills, and more severe autism symptoms as described by the parents, but not per the professional assessment. Macrocephaly was observed in 7.9% of the ASD population and did not differ from the normative HC group in any of the examined behavioral measures.
Based on these findings, two unique medical-behavioral subtypes in ASD that affect inherited traits of cognition and/or autism severity were suggested. The developmental regression phenotype occurred with widespread, more severe impairments in cognition, autism severity and adaptive skills, while the microcephaly phenotype occurred with more impaired cognition and adaptive skills. In contrast, severe food selectivity and sleep problems represent only comorbidities to ASD that affect functioning as manifested by lower adaptive skills. Defining specific subgroups in ASD with a unique biological signature and specific behavioral phenotypes may help future genetic and neuroscience research.