Cluster Analysis of Autistic Patients Based on Principal Pathogenetic Components

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 Res 2012,••:••–••. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

[1]  R. Płoski,et al.  [Polish version of the ADI-R (Autism Diagnostic Interview-Revised)]. , 2012, Psychiatria polska.

[2]  So Hyun Kim,et al.  Combining information from multiple sources for the diagnosis of autism spectrum disorders for toddlers and young preschoolers from 12 to 47 months of age. , 2012, Journal of child psychology and psychiatry, and allied disciplines.

[3]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[4]  Alison E Lane,et al.  Brief Report: Further Evidence of Sensory Subtypes in Autism , 2011, Journal of autism and developmental disorders.

[5]  Roger Bakeman,et al.  Support for a Dimensional View of Autism Spectrum Disorders in Toddlers , 2012, Journal of autism and developmental disorders.

[6]  M. Elia,et al.  Principal pathogenetic components and biological endophenotypes in autism spectrum disorders , 2010, Autism research : official journal of the International Society for Autism Research.

[7]  C. Arango.  Clinical subtyping and early detection: short-term challenges for child and adolescent psychiatry , 2010, European Child & Adolescent Psychiatry.

[8]  Клинические дисциплины.  Autism Diagnostic Observation Schedule , 2010 .

[9]  Jacob Vorstman,et al.  Dissecting the Clinical Heterogeneity of Autism Spectrum Disorders through Defined Genotypes , 2010, PloS one.

[10]  J. A. Van de Water,et al.  The immune system's role in the biology of autism , 2010, Current opinion in neurology.

[11]  C. Tinelli,et al.  An Autistic Endophenotype Results in Complex Immune Dysfunction in Healthy Siblings of Autistic Children , 2009, Biological Psychiatry.

[12]  Carrie Houts,et al.  The structure of the Autism Diagnostic Interview-Revised: diagnostic and phenotypic implications. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[13]  Vanessa Hus,et al.  The Autism Diagnostic Observation Schedule—Toddler Module: A New Module of a Standardized Diagnostic Measure for Autism Spectrum Disorders , 2009, Journal of autism and developmental disorders.

[14]  Valerie W. Hu,et al.  Novel clustering of items from the Autism Diagnostic Interview‐Revised to define phenotypes within autism spectrum disorders , 2009, Autism research : official journal of the International Society for Autism Research.

[15]  Joseph D. Buxbaum,et al.  Multiple rare variants in the etiology of autism spectrum disorders , 2009, Dialogues in clinical neuroscience.

[16]  Jessica Brian,et al.  Temperament and its Relationship to Autistic Symptoms in a High-Risk Infant Sib Cohort , 2009, Journal of abnormal child psychology.

[17]  T. Doetschman.  Influence of genetic background on genetically engineered mouse phenotypes. , 2009, Methods in molecular biology.

[18]  S. Orapeleng,et al.  An exploratory analysis of the use of cognitive, adaptive and behavioural indices for cluster analysis of ASD subgroups. , 2008, Journal of intellectual disability research : JIDR.

[19]  C. Lintas,et al.  Autistic phenotypes and genetic testing: state-of-the-art for the clinical geneticist , 2008, Journal of Medical Genetics.

[20]  H. Tager-Flusberg,et al.  Sensory clusters of toddlers with autism spectrum disorders: differences in affective symptoms. , 2008, Journal of child psychology and psychiatry, and allied disciplines.

[21]  S. Baron-Cohen,et al.  Behavioral and Brain Functions Clinical Heterogeneity among People with High Functioning Autism Spectrum Conditions: Evidence Favouring a Continuous Severity Gradient , 2008 .

[22]  T. Bourgeron,et al.  Abnormal melatonin synthesis in autism spectrum disorders , 2008, Molecular Psychiatry.

[23]  Gerome Breen,et al.  Behavioral and Brain Functions Dopamine-beta Hydroxylase Polymorphism and Cocaine Addiction , 2022 .

[24]  C. Lord,et al.  The Autism Diagnostic Observation Schedule: Revised Algorithms for Improved Diagnostic Validity , 2007, Journal of autism and developmental disorders.

[25]  Marcel Kinsbourne,et al.  Sensory and attention abnormalities in autistic spectrum disorders , 2006, Autism : the international journal of research and practice.

[26]  Anne Boomsma,et al.  Structural equation analysis of a hypothesised symptom model in the autism spectrum. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[27]  J. Lisý,et al.  Subtypes of autism by cluster analysis based on structural MRI data , 2005, European Child & Adolescent Psychiatry.

[28]  T. Kemper,et al.  Neuroanatomic observations of the brain in autism: a review and future directions , 2005, International Journal of Developmental Neuroscience.

[29]  A. Zimmerman,et al.  Neuroglial activation and neuroinflammation in the brain of patients with autism , 2005, Annals of neurology.

[30]  C. Barthélémy,et al.  Identification of behaviour profiles within a population of autistic children using multivariate statistical methods , 1995, European Child & Adolescent Psychiatry.

[31]  C. Barthélémy,et al.  Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research , 1995, European Child & Adolescent Psychiatry.

[32]  Stephanie Hayes,et al.  The factor structure of autistic traits. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[33]  C. Barthélémy,et al.  Behaviour profiles in a population of infants later diagnosed as having autistic disorder , 2004, European Child & Adolescent Psychiatry.

[34]  Helen Tager-Flusberg,et al.  A principal components analysis of the Autism Diagnostic Interview-Revised. , 2003, Journal of the American Academy of Child and Adolescent Psychiatry.

[35]  M A Pericak-Vance,et al.  Fine mapping of autistic disorder to chromosome 15q11‐q13 by use of phenotypic subtypes. , 2003, American journal of human genetics.

[36]  L. Lotspeich,et al.  Behavioral phenotypic variation in autism multiplex families: evidence for a continuous severity gradient. , 2002, American journal of medical genetics.

[37]  M. Stevens,et al.  Subgroups of children with autism by cluster analysis: a longitudinal examination. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[38]  Carl Feinstein,et al.  Subtypes of Pervasive Developmental Disorder: Clinical Characteristics* , 1999 .

[39]  David G. Stork,et al.  Pattern Classification (2nd ed.) , 1999 .

[40]  M. Prior,et al.  Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders. , 1998, Journal of child psychology and psychiatry, and allied disciplines.

[41]  C. Barthélémy,et al.  Bioclinical profiles of autism and other developmental disorders using a multivariate statistical approach , 1997, Biological Psychiatry.

[42]  U. Wolf.  Identical mutations and phenotypic variation , 1997, Human Genetics.

[43]  S Arndt,et al.  Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. , 1997, The American journal of psychiatry.

[44]  J. Matson,et al.  Empirically derived subtypes of pervasive developmental disorders: A cluster analytic study , 1995, Journal of autism and developmental disorders.

[45]  D. Curtis,et al.  Monte Carlo tests for associations between disease and alleles at highly polymorphic loci , 1995, Annals of human genetics.

[46]  L. Eaves,et al.  Subtypes of autism by cluster analysis , 1994, Journal of autism and developmental disorders.

[47]  Dc Washington.  Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. , 1994 .

[48]  S. Palazzi,et al.  Infantile autism and computerized tomography brain-scan findings: Specific versus nonspecific abnormalities , 1989, Journal of autism and developmental disorders.

[49]  H. Kraemer,et al.  Empirically derived subclassification of the autistic syndrome , 1986, Journal of autism and developmental disorders.

[50]  T. Oakland,et al.  A Review of the Vineland Adaptive Behavior Scales, Survey Form , 1985 .

[51]  L. Wing,et al.  Severe impairments of social interaction and associated abnormalities in children: Epidemiology and classification , 1979, Journal of autism and developmental disorders.