Cluster Analysis of Autistic Patients Based on Principal Pathogenetic Components


Address for correspondence and reprints: Antonio M. Persico, Lab. of Molecular Psychiatry & Neurogenetics, University “Campus Bio-Medico,” Via Alvaro del Portillo 21, I-00128 Rome, Italy. E-mail:


We have recently described four principal pathogenetic components in autism: (I) circadian and sensory dysfunction, (II) immune abnormalities, (III) neurodevelopmental delay, and (IV) stereotypic behaviors. Using hierarchical and k-means clustering, the same 245 patients assessed in our principal component analysis can be partitioned into four clusters: (a) 43 (17.6%) have prominent immune abnormalities accompanied by some circadian and sensory issues; (b) 44 (18.0%) display major circadian and sensory dysfunction, with little or no immune symptoms; (c) stereotypies predominate in 75 (31.0%); and (d) 83 (33.9%) show a mixture of all four components, with greater disruptive behaviors and mental retardation. The “immune” component provides the largest contributions to phenotypic variance (P = 2.7 x 10–45), followed by “stereotypic behaviors.” These patient clusters may likely differ in genetic and immune underpinnings, developmental trajectories, and response to treatment. Autism Res2012,••:••–••. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.