title: Tumor necrosis factor-alpha expression in peripheral blood mononuclear cells correlates with early childhood social interaction in autism spectrum disorder.
abstract: Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines. Since social experience of children with autism spectrum disorder is generally unlike to typically developing children, we hypothesized that social interaction during childhood contribute to pro-inflammatory cytokine expression in subjects with autism spectrum disorder. We compared revised Autism Diagnostic Interview scores and expression levels of pro-inflammatory cytokines in peripheral blood mononuclear cells of subjects with autism spectrum disorder (n = 30). The score of domain A on the revised Autism Diagnostic Interview, indicating social interaction impairment in early childhood, was negatively correlated with tumor necrosis factor-α mRNA expression level in peripheral blood mononuclear cells but not interleukin-1β or -6. Consistently, tumor necrosis factor-α mRNA expression was markedly low in subjects with autism spectrum disorder compared to typically developing children who presumably experienced the regular levels of social interaction. These findings suggest that the low blood levels of tumor necrosis factor-α mRNA in subjects with autism spectrum disorder might be due to impaired social interaction in early childhood.
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan. Electronic address: mmm@naramed-u.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Makinodan
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Japan; Department of Development of Functional Brain Activities, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ikawa
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamuro
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Toritsuka
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Sohei
authors.initials: S
authors.lastname: Kimoto
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Takahira
authors.initials: T
authors.lastname: Yamauchi
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Department of Faculty of Sociology, Chukyo University, Toyota, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.affiliation: Aichi Children's Health and Medical Center, Obu, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Japan; Department of Development of Functional Brain Activities, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Nara, 634-8522, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000097:blood*; D002648:Child; D016207:Cytokines / Q000097:blood; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007398:Interpersonal Relations; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: Autism spectrum disorder; Childhood; Peripheral blood mononuclear cells; Social interaction; Tumor necrosis factor-α