title: Common infections with polyomaviruses and herpesviruses and neuropsychological development at 4 years of age, the Rhea birth cohort in Crete, Greece.
abstract: Viral infections of the central nervous system may have detrimental effects for the developing brain, but the effects of less virulent common infections are unclear. We aim to investigate the impact of common viral infections of early childhood on neuropsychological performance of children at age four.
  
  
  
  We used cross-sectional data on 674 children participating at the 4 years of age follow-up of the Rhea birth cohort in Crete, Greece. Blood levels of IgG antibodies to 10 polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, HPyV6, HPyV7, TSPyV, MCPyV, HPyV9, and HPyV10) and four herpesviruses [Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and herpes simplex virus-2 (HSV-2)] were measured using multiplex serology. Child's neuropsychological development at age four was assessed using the McCarthy Scales of Children's Abilities, the Attention-Deficit Hyperactivity Disorder Test (ADHDT), and the Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression models were used to explore the associations.
  
  
  
  Seroprevalence to polyomaviruses ranged from 21% for HPyV9 to 82% for HPyV10. Seroprevalence for EBV was 53%, for CMV 26%, for HSV-1 3.6%, and for HSV-2 1.5%. Children seropositive to ≥8 polyomaviruses had lower score in ADHDT inattention subscale [β = -1.28 (95% CI: -2.56, -0.001)] and lower score in SDQ hyperactivity-inattention subscale [β = -.99 (95% CI: -1.60, -0.37)] versus children seropositive to ≤3 polyomaviruses. Seropositivity to BKPyV, a potential neurotropic virus, was associated with higher score in ADHDT inattention subscale [β = .87 (95% CI: 0.03, 1.71)].
  
  
  
  These findings suggest that acquisition of polyomaviruses during development may influence behavioral outcomes in early childhood.
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Karachaliou
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Leda
authors.initials: L
authors.lastname: Chatzi
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Theano
authors.initials: T
authors.lastname: Roumeliotaki
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Mariza
authors.initials: M
authors.lastname: Kampouri
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Andriani
authors.initials: A
authors.lastname: Kyriklaki
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Koutra
authors.affiliation: Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chalkiadaki
authors.affiliation: Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Michel
authors.affiliation: Department of Pediatric Hematology-Oncology University of Crete, University Hospital of Heraklion, Heraklion, Greece.
authors.forename: Eftichia
authors.initials: E
authors.lastname: Stiakaki
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. s.sanjose@iconcologia.net.|Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, L'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain. s.sanjose@iconcologia.net.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjose
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000453:epidemiology*; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D002658:Developmental Disabilities / Q000097:blood / Q000453:epidemiology*; D005260:Female; D006115:Greece / Q000453:epidemiology; D006566:Herpesviridae Infections / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D008297:Male; D027601:Polyomavirus Infections / Q000097:blood / Q000453:epidemiology*; D016036:Seroepidemiologic Studies
keywords: Attention-deficit/hyperactivity disorder; epidemiologic studies; neural development; preschool children