{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:38:13Z","timestamp":1789349893107,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2010,9,27]],"date-time":"2010-09-27T00:00:00Z","timestamp":1285545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010degree relatives. Using a stepwise approach, patient and family history variables were analyzed using principal component analysis (\u201cexploratory phase\u201d), followed by intra\u2010 and inter\u2010component cross\u2010correlation analyses (\u201cfollow\u2010up phase\u201d), and by testing for association between each component and biological endophenotypes, namely head circumference, serotonin blood levels, and global urinary peptide excretion rates (\u201cbiological correlation phase\u201d). Four independent components were identified, namely \u201ccircadian &amp; sensory dysfunction,\u201d \u201cimmune dysfunction,\u201d \u201cneurodevelopmental delay,\u201d and \u201cstereotypic behavior,\u201d 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.<\/jats:p>","DOI":"10.1002\/aur.151","type":"journal-article","created":{"date-parts":[[2010,9,27]],"date-time":"2010-09-27T19:03:20Z","timestamp":1285614200000},"page":"237-252","source":"Crossref","is-referenced-by-count":89,"title":["Principal pathogenetic components and biological endophenotypes in autism spectrum 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