Autism spectrum disorder and schizophrenia: An updated conceptual review

Abstract

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate disorders, with distinct clinical profiles and natural histories. ASD, typically diagnosed in childhood, is characterized by restricted or repetitive interests or behaviors and impaired social communication, and it tends to have a stable course. SCZ, typically diagnosed in adolescence or adulthood, is characterized by hallucinations and delusions, and tends to be associated with declining function. However, youth with ASD are three to six times more likely to develop SCZ than their neurotypical counterparts, and increasingly, research has shown that ASD and SCZ converge at several levels. We conducted a systematic review of studies since 2013 relevant to understanding this convergence, and present here a narrative synthesis of key findings, which we have organized into four broad categories: symptoms and behavior, perception and cognition, biomarkers, and genetic and environmental risk. We then discuss opportunities for future research into the phenomenology and neurobiology of overlap between ASD and SCZ. Understanding this overlap will allow for researchers, and eventually clinicians, to understand the factors that may make a child with ASD vulnerable to developing SCZ. Lay Summary Autism spectrum disorder and schizophrenia are distinct diagnoses, but people with autism and people with schizophrena share several characteristics. We review recent studies that have examined these areas of overlap, and discuss the kinds of studies we will need to better understand how these disorders are related. Understanding this will be important to help us identify which autistic children are at risk of developing schizophrenia.

Association between increased anterior cingulate glutamate and psychotic-like symptoms, but not autistic traits

“…The greatest difference between the disorders, however, lies within the type of positive symptoms: While individuals with ASD may show repetitive or restricted behaviours, individuals with schizophrenia may suffer from hallucinations or delusions (10). Despite those differences, both disorders share common environmental risk factors, genetic predispositions as well as neuronal abnormalities (7,11). Patients with ASD and schizophrenia show, for example, abnormal development in the anterior cingulate cortex (ACC), striatum and frontal lobe (12)(13)(14).…”

“…Despite those differences, both disorders share common environmental risk factors, genetic predispositions as well as neuronal abnormalities (7,11). Patients with ASD and schizophrenia show, for example, abnormal development in the anterior cingulate cortex (ACC), striatum and frontal lobe (12–14).…”

“…Already in the earliest clinical reports of schizophrenia and autism spectrum disorder (ASD), their commonalities and associations have been discussed (1)(2)(3) . On a phenomenological level, schizophrenia and ASD overlap regarding negative symptoms, social cognition, and perceptual alterations (4). Additionally, both disorders display similar cognitive deficits in terms of working memory function, perspective taking, or response inhibition (5).…”

Exploring clozapine use in severe psychiatric symptoms associated with autism spectrum disorder: A scoping review

“…Given these therapeutic correspondences, it is tempting to conjecture that clozapine may act on neural mechanisms common to both conditions. The hypothesis of a psychopathological overlap or continuum between ASD and schizophrenia is not new (Chisholm et al, 2015; Jutla et al, 2022; King and Lord, 2011; Owen and O’Donovan, 2017), which also encompasses abnormalities associated with social cognition (Barlati et al, 2020; Isvoranu et al, 2022). However, whether the improved social behavior is linked to the attenuation of psychiatric symptoms or whether they manifest autonomously remains elusive.…”

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study

“…Previous studies have highlighted the substantial overlap between ASD and SCZ at genetic (53) , neural (54) , and behavioral levels (55) . However, these findings are less replicable due to methodological differences (56) . In contrast, we reproduced the asymmetric proximity between the ASD and SCZ group, whereby the SCZ group manifested stronger adjacency to the ASD group than the TDC group on the ASD neuromarker, whereas the ASD group displayed stronger proximity to the TDC group than the SCZ group on the SCZ neuromarker, by using different datasets and methods (36) .…”