Autistic Disorders and Schizophrenia: Related or Remote? An Anatomical Likelihood Estimation

Abstract

Shared genetic and environmental risk factors have been identified for autistic spectrum disorders (ASD) and schizophrenia. Social interaction, communication, emotion processing, sensorimotor gating and executive function are disrupted in both, stimulating debate about whether these are related conditions. Brain imaging studies constitute an informative and expanding resource to determine whether brain structural phenotype of these disorders is distinct or overlapping. We aimed to synthesize existing datasets characterizing ASD and schizophrenia within a common framework, to quantify their structural similarities. In a novel modification of Anatomical Likelihood Estimation (ALE), 313 foci were extracted from 25 voxel-based studies comprising 660 participants (308 ASD, 352 first-episode schizophrenia) and 801 controls. The results revealed that, compared to controls, lower grey matter volumes within limbic-striato-thalamic circuitry were common to ASD and schizophrenia. Unique features of each disorder included lower grey matter volume in amygdala, caudate, frontal and medial gyrus for schizophrenia and putamen for autism. Thus, in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms. However, the distinctive neuroanatomy also mapped in each condition raises the question about how this is arrived in the context of common etiological pressures.

Long-term pathological consequences of prenatal infection: beyond brain disorders

“…In this sense, the adverse effects induced by prenatal infection may reflect an early entry into a deviant neurodevelopmental route, but the specificity of subsequent disease or symptoms is likely to be influenced by the genetic and environmental context in which the prenatal infectious process occurs. This concept would, indeed, be consistent with the emerging evidence suggesting that seemingly remote disorders, such as schizophrenia, autism, attention-deficit/hyperactivity disorder, and major depression share considerable amounts of risk factors and brain dysfunctions (23,92,138). The presence of shared genetic and environmental risks among those illnesses has led to the proposal that they might lie along a continuum of genetically and environmentally induced neurodevelopmental causalities (103,113), wherein prenatal infection may be one of the many factors that shape the eventual pathological outcomes.…”

Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

“…Interestingly, a recent meta-analysis showed that insular and cingulate deficits are shared among individuals with schizophrenia or autism-spectrum disorders, though some hemispheric differences in terms of more left lateralized deficits may occur in individuals with schizophrenia. 57 This meta-analysis included mostly studies with neuroleptic-naïve participants, though the psychotic symptom burden among autistic individuals was not reported. Further, a prominent role for the anterior insula in the social processing defects of autism-spectrum disorders has been proposed on the basis of various functional magnetic resonance imaging (fMRI) studies.…”

Can Asperger syndrome be distinguished from autism? An anatomic likelihood meta-analysis of MRI studies

“…Moreover, ALE can be used to extract information about neuroanatomic overlap in related conditions. [54][55][56] Building on this application of ALE, we scrutinized the available literature to establish the relative proportion of participants with Asperger syndrome and autism in each VBM study of grey matter volume in people with autism spectrum disorders. It was possible to categorize the study samples as either entirely or predominantly people with Asperger syndrome or autism.…”