Autism Spectrum Disorder in 2023: A Challenge Still Open

Abstract

In this paper, we provide an update on autism spectrum disorder (ASD), including epidemiology, etiopathogenesis, clinical presentation, instrumental investigations, early signs, onset patterns, neuropsychological hypotheses, treatments, and long-term outcome. The prevalence of this condition has increased enormously over the last few decades. This increase prompted a search for possible environmental factors whose effects would add up to a genetic predisposition leading to the development of autism. But the genetic and environmental variables involved are extremely numerous, and conclusive data regarding the etiopathogenesis are still far away. Assuming that a well-defined etiology is still found today only in a minority of cases, numerous pathogenetic mechanisms have been hypothesized. Among these, we mention oxidative stress, mitochondrial dysfunction, alteration of the intestinal microbiota, immune dysregulation, and neuroinflammation. These pathogenetic mechanisms could alter epigenetic status and gene expression, finally leading to ASD. Inherent in the term spectrum is the great clinical heterogeneity of this condition, mainly due to the frequent comorbidity that characterizes it. The earlier the diagnosis is made and the earlier psychoeducational treatment begins, the better the prognosis. In this sense, the role of pediatricians can be decisive in making children with signs suggestive of autism undergo a specialist diagnostic course. The development of increasingly advanced cognitive-behavioral educational techniques has considerably improved the prognosis of affected individuals, even though only a small minority of them come off the autistic spectrum. Pharmacological therapies are used to treat comorbidities. During childhood, the most important prognostic factor for long-term outcome seems to be intellectual functioning.

Possible Overestimation of Comorbid Oppositional Defiant Disorder in Autism Spectrum Disorder

“…Oppositional defiant disorder is one of the many neuropsychiatric comorbidities reported in individuals with autism spectrum disorder (ASD), along with intellectual disability, attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, and depressive disorders. 2 , 3 Depending on the studies available in the literature, the recurrence of ODD reported in children and adolescents with ASD varies greatly from approximately 7% to 75%, most likely due to the different methodologies used. However, according to most studies, it is higher than 20%.…”

“…Indeed, the symptoms that characterize ODD could at least partly find an explanation in the context of the complex clinical picture presented by individuals with ASD. For example, when a child with ASD perceives very unpleasant sensations (e.g., in a crowded and noisy environment or when faced with highly disturbing visual stimuli) due to his/her own sensory abnormalities (so frequent in these patients), 3 , 8 he/she may present intense and stubborn manifestations of rejection toward the situation experienced, associated with apparently inexplicable reactions of anger toward the persons around him/her. These symptoms can mimic the clinical picture of ODD, particularly in younger children who are unable to communicate verbally.…”

“…Finally, the above-mentioned could have an even broader value, not limited only to ODD, as it suggests caution in using in general the concept of comorbidity in a clinically complex and heterogeneous pathological condition such as ASD. 3 , 10 A global (so to speak, “holistic”) approach to the child with ASD, which allows the various problems present to be addressed without keeping them separate, appears to be the most appropriate to meet the needs that this condition entails.…”