One Hundred Years of Insanity: Genomic, Psychological, and Evolutionary Models of Autism in Relation to Schizophrenia

Abstract

The Swiss psychiatrist Eugen Bleuler coined the terms 'schizophrenia', for the splitting of psychic functions, and 'autism', for withdrawal from external reality in patients with schizophrenia, almost exactly a century ago. Ever since 1943 when Leo Kanner co-opted 'autism' to refer to a new condition involving 'disturbance of affective contact' manifested in children, the relationship between schizophrenia and Kanner's autism has remained unclear. In this article I draw on data from studies of genomics, neurodevelopment, psychology, psychiatry and evolutionary biology to develop and evaluate alternative hypotheses for the relationship between autism and schizophrenia spectrum conditions. These data provide evidence for two hypotheses: partially-overlapping etiology of autism with schizophrenia mediated by common risk factors, and diametric causes of autism and schizophrenia mediated by genes underlying under-development versus dysregulated over-development of human social-brain phenotypes. The primary 1 practical implications of these results are that: (1) false-positive diagnoses of premorbidity to schizophrenia-spectrum conditions as autistic spectrum conditions may be common, and may indicate a structural flaw in current diagnostic, nosological frameworks, (2) schizophrenia may be due in part to losses of function in negative regulators of social cognition and affect, rather than deficits in brain development; (3) the development of new pharmacological treatments for autism and schizophrenia can benefit directly from models of how autistic spectrum and schizophrenia spectrum conditions are etiologically related; and (4) future studies of autism, schizophrenia, and their relationship to one another must increasingly seek to integrate across analytic levels, from genes to neurodevelopment, neurological function, neuroanatomy, cognition, and evolutionary biology of the social brain, in the context of subtyping the substantial genetic and clinical heterogeneity found in each set of conditions.