Principal pathogenetic components and biological endophenotypes in autism spectrum disorders

Roberto Sacco, Paolo Curatolo, Barbara Manzi, Roberto Militerni, Carmela Bravaccio, Alessandro Frolli, Carlo Lenti, Monica Saccani, Maurizio Elia, Karl Ludvig Reichelt, Tiziana Pascucci, Stefano Puglisi-Allegra, Antonio M. Persico

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. The aim of this study is to begin identifying at least some of these components and to assess their association with biological endophenotypes. To address this issue, we recruited 245 Italian patients with idiopathic autism spectrum disorders and their first-degree relatives. Using a stepwise approach, patient and family history variables were analyzed using principal component analysis ("exploratory phase"), followed by intra- and inter-component cross-correlation analyses ("follow-up phase"), and by testing for association between each component and biological endophenotypes, namely head circumference, serotonin blood levels, and global urinary peptide excretion rates ("biological correlation phase"). Four independent components were identified, namely "circadian & sensory dysfunction," "immune dysfunction," "neurodevelopmental delay," and "stereotypic behavior," together representing 74.5% of phenotypic variance in our sample. Marker variables in the latter three components are positively associated with macrocephaly, global peptiduria, and serotonin blood levels, respectively. These four components point toward at least four processes associated with autism, namely (I) a disruption of the circadian cycle associated with behavioral and sensory abnormalities, (II) dysreactive immune processes, surprisingly linked both to prenatal obstetric complications and to excessive postnatal body growth rates, (III) a generalized developmental delay, and (IV) an abnormal neural circuitry underlying stereotypies and early social behaviors.

Original languageEnglish
Pages (from-to)237-252
Number of pages16
JournalAutism Research
Volume3
Issue number5
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Endophenotypes
Autistic Disorder
Serotonin
Megalencephaly
Social Behavior
Principal Component Analysis
Obstetrics
Head
Peptides
Growth
Autism Spectrum Disorder
Neurodevelopmental Disorders

Keywords

  • Autistic disorder
  • Macrocephaly
  • Neurodevelopment
  • Pervasive developmental disorders
  • Principal component analysis
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)

Cite this

Sacco, R., Curatolo, P., Manzi, B., Militerni, R., Bravaccio, C., Frolli, A., ... Persico, A. M. (2010). Principal pathogenetic components and biological endophenotypes in autism spectrum disorders. Autism Research, 3(5), 237-252. https://doi.org/10.1002/aur.151

Principal pathogenetic components and biological endophenotypes in autism spectrum disorders. / Sacco, Roberto; Curatolo, Paolo; Manzi, Barbara; Militerni, Roberto; Bravaccio, Carmela; Frolli, Alessandro; Lenti, Carlo; Saccani, Monica; Elia, Maurizio; Reichelt, Karl Ludvig; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Persico, Antonio M.

In: Autism Research, Vol. 3, No. 5, 10.2010, p. 237-252.

Research output: Contribution to journalArticle

Sacco, R, Curatolo, P, Manzi, B, Militerni, R, Bravaccio, C, Frolli, A, Lenti, C, Saccani, M, Elia, M, Reichelt, KL, Pascucci, T, Puglisi-Allegra, S & Persico, AM 2010, 'Principal pathogenetic components and biological endophenotypes in autism spectrum disorders', Autism Research, vol. 3, no. 5, pp. 237-252. https://doi.org/10.1002/aur.151
Sacco R, Curatolo P, Manzi B, Militerni R, Bravaccio C, Frolli A et al. Principal pathogenetic components and biological endophenotypes in autism spectrum disorders. Autism Research. 2010 Oct;3(5):237-252. https://doi.org/10.1002/aur.151
Sacco, Roberto ; Curatolo, Paolo ; Manzi, Barbara ; Militerni, Roberto ; Bravaccio, Carmela ; Frolli, Alessandro ; Lenti, Carlo ; Saccani, Monica ; Elia, Maurizio ; Reichelt, Karl Ludvig ; Pascucci, Tiziana ; Puglisi-Allegra, Stefano ; Persico, Antonio M. / Principal pathogenetic components and biological endophenotypes in autism spectrum disorders. In: Autism Research. 2010 ; Vol. 3, No. 5. pp. 237-252.
@article{7f3d54bd717b445486e4a336b6f9c86a,
title = "Principal pathogenetic components and biological endophenotypes in autism spectrum disorders",
abstract = "Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. The aim of this study is to begin identifying at least some of these components and to assess their association with biological endophenotypes. To address this issue, we recruited 245 Italian patients with idiopathic autism spectrum disorders and their first-degree relatives. Using a stepwise approach, patient and family history variables were analyzed using principal component analysis ({"}exploratory phase{"}), followed by intra- and inter-component cross-correlation analyses ({"}follow-up phase{"}), and by testing for association between each component and biological endophenotypes, namely head circumference, serotonin blood levels, and global urinary peptide excretion rates ({"}biological correlation phase{"}). Four independent components were identified, namely {"}circadian & sensory dysfunction,{"} {"}immune dysfunction,{"} {"}neurodevelopmental delay,{"} and {"}stereotypic behavior,{"} together representing 74.5{\%} of phenotypic variance in our sample. Marker variables in the latter three components are positively associated with macrocephaly, global peptiduria, and serotonin blood levels, respectively. These four components point toward at least four processes associated with autism, namely (I) a disruption of the circadian cycle associated with behavioral and sensory abnormalities, (II) dysreactive immune processes, surprisingly linked both to prenatal obstetric complications and to excessive postnatal body growth rates, (III) a generalized developmental delay, and (IV) an abnormal neural circuitry underlying stereotypies and early social behaviors.",
keywords = "Autistic disorder, Macrocephaly, Neurodevelopment, Pervasive developmental disorders, Principal component analysis, Serotonin",
author = "Roberto Sacco and Paolo Curatolo and Barbara Manzi and Roberto Militerni and Carmela Bravaccio and Alessandro Frolli and Carlo Lenti and Monica Saccani and Maurizio Elia and Reichelt, {Karl Ludvig} and Tiziana Pascucci and Stefano Puglisi-Allegra and Persico, {Antonio M.}",
year = "2010",
month = "10",
doi = "10.1002/aur.151",
language = "English",
volume = "3",
pages = "237--252",
journal = "Autism Research",
issn = "1939-3806",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Principal pathogenetic components and biological endophenotypes in autism spectrum disorders

AU - Sacco, Roberto

AU - Curatolo, Paolo

AU - Manzi, Barbara

AU - Militerni, Roberto

AU - Bravaccio, Carmela

AU - Frolli, Alessandro

AU - Lenti, Carlo

AU - Saccani, Monica

AU - Elia, Maurizio

AU - Reichelt, Karl Ludvig

AU - Pascucci, Tiziana

AU - Puglisi-Allegra, Stefano

AU - Persico, Antonio M.

PY - 2010/10

Y1 - 2010/10

N2 - Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. The aim of this study is to begin identifying at least some of these components and to assess their association with biological endophenotypes. To address this issue, we recruited 245 Italian patients with idiopathic autism spectrum disorders and their first-degree relatives. Using a stepwise approach, patient and family history variables were analyzed using principal component analysis ("exploratory phase"), followed by intra- and inter-component cross-correlation analyses ("follow-up phase"), and by testing for association between each component and biological endophenotypes, namely head circumference, serotonin blood levels, and global urinary peptide excretion rates ("biological correlation phase"). Four independent components were identified, namely "circadian & sensory dysfunction," "immune dysfunction," "neurodevelopmental delay," and "stereotypic behavior," together representing 74.5% of phenotypic variance in our sample. Marker variables in the latter three components are positively associated with macrocephaly, global peptiduria, and serotonin blood levels, respectively. These four components point toward at least four processes associated with autism, namely (I) a disruption of the circadian cycle associated with behavioral and sensory abnormalities, (II) dysreactive immune processes, surprisingly linked both to prenatal obstetric complications and to excessive postnatal body growth rates, (III) a generalized developmental delay, and (IV) an abnormal neural circuitry underlying stereotypies and early social behaviors.

AB - Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. The aim of this study is to begin identifying at least some of these components and to assess their association with biological endophenotypes. To address this issue, we recruited 245 Italian patients with idiopathic autism spectrum disorders and their first-degree relatives. Using a stepwise approach, patient and family history variables were analyzed using principal component analysis ("exploratory phase"), followed by intra- and inter-component cross-correlation analyses ("follow-up phase"), and by testing for association between each component and biological endophenotypes, namely head circumference, serotonin blood levels, and global urinary peptide excretion rates ("biological correlation phase"). Four independent components were identified, namely "circadian & sensory dysfunction," "immune dysfunction," "neurodevelopmental delay," and "stereotypic behavior," together representing 74.5% of phenotypic variance in our sample. Marker variables in the latter three components are positively associated with macrocephaly, global peptiduria, and serotonin blood levels, respectively. These four components point toward at least four processes associated with autism, namely (I) a disruption of the circadian cycle associated with behavioral and sensory abnormalities, (II) dysreactive immune processes, surprisingly linked both to prenatal obstetric complications and to excessive postnatal body growth rates, (III) a generalized developmental delay, and (IV) an abnormal neural circuitry underlying stereotypies and early social behaviors.

KW - Autistic disorder

KW - Macrocephaly

KW - Neurodevelopment

KW - Pervasive developmental disorders

KW - Principal component analysis

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=79251485318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251485318&partnerID=8YFLogxK

U2 - 10.1002/aur.151

DO - 10.1002/aur.151

M3 - Article

VL - 3

SP - 237

EP - 252

JO - Autism Research

JF - Autism Research

SN - 1939-3806

IS - 5

ER -