title: Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults.
abstract: BACKGROUND
  Characterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism.
  
  
  RESULTS
  Our data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology.
  
  
  CONCLUSIONS
  The most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wegiel
authors.forename: Michael
authors.initials: M
authors.lastname: Flory
authors.forename: Izabela
authors.initials: I
authors.lastname: Kuchna
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Nowicki
authors.forename: Shuang Yong
authors.initials: SY
authors.lastname: Ma
authors.forename: Humi
authors.initials: H
authors.lastname: Imaki
authors.forename: Jarek
authors.initials: J
authors.lastname: Wegiel
authors.forename: Janusz
authors.initials: J
authors.lastname: Frackowiak
authors.forename: Bozena Mazur
authors.initials: BM
authors.lastname: Kolecka
authors.forename: Teresa
authors.initials: T
authors.lastname: Wierzba-Bobrowicz
authors.forename: Eric
authors.initials: E
authors.lastname: London
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001321:Autistic Disorder / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D012720:Severity of Illness Index; D055815:Young Adult