Cerebellar Contributions to Cerebral Connectivity in Severe Mental Illness: A Developmental Cascade and...

Severe mental illness (SMI) includes neuropsychiatric disorders of adult onset, but also those that begin to show symptoms in adolescence and early childhood. This review treats the psychotic spectrum disorders and autism as neurodevelopmental in origin, each arising from perturbation of early brain development rather than from a process beginning at the age of clinical presentation. Grouping them is a claim about developmental origin and not about shared pathogenesis: they differ in the nature and timing of the perturbation and in the cortical systems being organized when it occurs. The diversity of social, language, behavioral, and cognitive symptoms and traits observed within this class is now well recognized. The language adopted to recognize such diversity has employed the term "spectrum" (e.g., autism spectrum disorder (ASD) and schizophrenia or psychotic spectrum). The substantial expansion of structural and functional connectivity research over the past 40 years has shown that both ASD and psychotic spectrum disorders have also been conceptualized as disorders of brain circuitry. Moreover, and particularly for ASD, this research was developed within a diagnostic time frame that itself underwent six revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), from the third edition (DSM-III; 1980) to the fifth edition, text revision (DSM-5-TR; 2022), with the largest changes involving the elimination of the early language onset requirement and the consolidation of prior subtypes into a single autism spectrum disorder. The present review develops a mechanistic account of cerebral connectivity differences in autistic disorder as defined under DSM-III and DSM-IV, where diagnostic practice, and in particular the exclusion of clinically significant language delay from Asperger's disorder, enriched cohorts for a subgroup in which cerebellar vermal lobule VI and VII abnormality, posterior callosal reduction, and atypical predictive processing were originally identified. The present account proposes, as a hypothesis rather than as an established finding, that deviation of vermal lobules VI and VII from typical development, in the direction of either hypoplasia or hyperplasia, both reported within the same DSM-III/IV cohort, and on evidence consistent with prenatal origin, initiates a developmental cascade that may shape postnatal cerebral connectivity through disinhibition of deep cerebellar nuclei and altered excitatory drive to thalamocortical circuits during sensitive periods. Cross-condition evidence indicates that vermal abnormality also occurs in conditions with distinct primary diagnoses (Joubert syndrome, fragile X, Rett syndrome, Williams syndrome, schizophrenia), producing the autistic-disorder cluster only when the upstream perturbation also affects cortical context-integration substrates at the relevant developmental window. These conditions are treated as further instances of a common neurodevelopmental class rather than as separate kinds of disorder, with autistic disorder as the focal case because it is where the vermal findings were first identified. Transdiagnostic connectivity evidence spanning autism and schizophrenia cohorts is examined to establish whether the cerebellar account generalizes across the SMI class or is specific to autistic disorder, and the regional and directional distribution of the cerebellar findings in each condition is treated as the discriminating variable. The framework proposes the cerebellum as a substrate for predictive internal models scaffolding auditory, social, and contextual learning, and is empirically testable through infant connectivity and event-related potential studies and through stratified re-analysis of multisite samples.