Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence.
Humans have systematic sex differences in brain-related behavior, cognition, and pattern of mental illness risk. Many of these differences emerge during adolescence, a developmental period of intense neurostructural and endocrine change. Here, by creating "movies" of sexually dimorphic brain development using longitudinal in vivo structural neuroimaging, we show regionally specific sex differences in development of the cerebral cortex during adolescence. Within cortical subsystems known to underpin domains of cognitive behavioral sex difference, structural change is faster in the sex that tends to perform less well within the domain in question. By stratifying participants through molecular analysis of the androgen receptor gene, we show that possession of an allele conferring more efficient functioning of this sex steroid receptor is associated with "masculinization" of adolescent cortical maturation. Our findings extend models first established in rodents, and suggest that in humans too, sex and sex steroids shape brain development in a spatiotemporally specific manner, within neural systems known to underpin sexually dimorphic behaviors.
Raznahan
Armin
A
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. raznahana@mail.nih.gov
Lee
Yohan
Y
Stidd
Reva
R
Long
Robert
R
Greenstein
Dede
D
Clasen
Liv
L
Addington
Anjene
A
Gogtay
Nitin
N
Rapoport
Judith L
JL
Giedd
Jay N
JN
D000293:Adolescent; D000294:Adolescent Behavior; D041923:Adolescent Development; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D012737:Sex Factors; D015398:Signal Transduction
D000728:Androgens; D011944:Receptors, Androgen