Sex differences in the effect of puberty on hippocampal morphology.

OBJECTIVE Puberty is the defining process of adolescence, and is accompanied by divergent trajectories of behavior and cognition for males and females. Here we examine whether sex differences exist in the effect of puberty on the morphology of the hippocampus and amygdala. METHOD T1-weighted structural neuroimaging was performed in a sample of 524 pre- or postpubertal individuals ages 10 to 22 years. Hippocampal and amygdala volume and shape were quantified using the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) FIRST procedure and scaled by intracranial volume. The effects on regional volume of age, sex, puberty, and their interactions were examined using linear regression. Postpubertal sex differences were examined using a vertex analysis. RESULTS Prepubertal males and females had similar hippocampal volumes, whereas postpubertal females had significantly larger bilateral hippocampi, resulting in a significant puberty-by-sex interaction even when controlling for age and age-by-sex. This effect was regionally specific and was not apparent in the amygdala. Vertex analysis revealed that postpubertal differences were most prominent in the lateral aspect of the hippocampus bilaterally, corresponding to the CA1 subfield. CONCLUSIONS These results establish that there are regionally specific sex differences in the effect of puberty on the hippocampus. These findings are relevant for the understanding of psychiatric disorders that have both hippocampal dysfunction and prominent gender disparities during adolescence.

[1]  C. Woolley,et al.  Gonadal hormone modulation of dendrites in the mammalian CNS. , 2005, Journal of neurobiology.

[2]  C. Roselli,et al.  Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system. , 1985, Endocrinology.

[3]  S. Nolen-Hoeksema,et al.  The emergence of gender differences in depression during adolescence. , 1994, Psychological bulletin.

[4]  Satrajit S. Ghosh,et al.  Nipype: A Flexible, Lightweight and Extensible Neuroimaging Data Processing Framework in Python , 2011, Front. Neuroinform..

[5]  T. Paus,et al.  Why do many psychiatric disorders emerge during adolescence? , 2008, Nature Reviews Neuroscience.

[6]  Jagath C. Rajapakse,et al.  Sexual dimorphism of the developing human brain , 1997, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[7]  Robert J. Handa,et al.  An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol , 2008, Hormones and Behavior.

[8]  Ross Ihaka,et al.  Gentleman R: R: A language for data analysis and graphics , 1996 .

[9]  F. Naftolin,et al.  Sexual differentiation of the central nervous system. , 1981, Science.

[10]  Martijn P. van den Heuvel,et al.  Sex steroids and connectivity in the human brain: A review of neuroimaging studies , 2011, Psychoneuroendocrinology.

[11]  C. Kellogg,et al.  Brain Androgen-Inducible Aromatase Is Critical for Adolescent Organization of Environment-Specific Social Interaction in Male Rats , 1999, Hormones and Behavior.

[12]  A. Addington,et al.  Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence , 2010, Proceedings of the National Academy of Sciences.

[13]  O. Rønnekleiv,et al.  Anatomic distribution and regulation of aromatase gene expression in the rat brain. , 1998, Biology of reproduction.

[14]  Stephen M. Smith,et al.  A Bayesian model of shape and appearance for subcortical brain segmentation , 2011, NeuroImage.

[15]  Kiralee M. Hayashi,et al.  Dynamic mapping of normal human hippocampal development , 2006, Hippocampus.

[16]  D. Louis Collins,et al.  Volumetric analysis of medial temporal lobe structures in brain development from childhood to adolescence , 2013, NeuroImage.

[17]  Gereon R Fink,et al.  Sex differences and the impact of steroid hormones on the developing human brain. , 2009, Cerebral cortex.

[18]  Ivo D Dinov,et al.  Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity. , 2011, Cerebral cortex.

[19]  T. Hare,et al.  The Adolescent Brain , 2008, Annals of the New York Academy of Sciences.

[20]  Dinggang Shen,et al.  Puberty-related influences on brain development , 2006, Molecular and Cellular Endocrinology.

[21]  B. Luna.  Developmental changes in cognitive control through adolescence. , 2009, Advances in child development and behavior.

[22]  N. M. Morris,et al.  Validation of a self-administered instrument to assess stage of adolescent development , 1980, Journal of youth and adolescence.

[23]  L. Somerville,et al.  Developmental neurobiology of cognitive control and motivational systems , 2010, Current Opinion in Neurobiology.

[24]  Dorret I. Boomsma,et al.  Sex steroids and brain structure in pubertal boys and girls , 2009, Psychoneuroendocrinology.

[25]  J. Fudge,et al.  A developmental neurobiological model of motivated behavior: Anatomy, connectivity and ontogeny of the triadic nodes , 2009, Neuroscience & Biobehavioral Reviews.

[26]  Daniel S. Marcus,et al.  The extensible neuroimaging archive toolkit , 2007, Neuroinformatics.

[27]  G. H. Glover,et al.  Pubertal stage and brain anatomy in girls , 2012, Neuroscience.

[28]  Paul M. Thompson,et al.  Sexual dimorphism of brain developmental trajectories during childhood and adolescence , 2007, NeuroImage.

[29]  Raquel E Gur,et al.  Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21. , 2012, Neuropsychology.

[30]  Mark A. Elliott,et al.  Being right is its own reward: Load and performance related ventral striatum activation to correct responses during a working memory task in youth , 2012, NeuroImage.

[31]  Gregory F Ball,et al.  Sex Differences in the Brain: The Not So Inconvenient Truth , 2012, The Journal of Neuroscience.

[32]  Peter E. Wais,et al.  The Hippocampus Supports both the Recollection and the Familiarity Components of Recognition Memory , 2006, Neuron.

[33]  Y. Arai,et al.  Organizational action of estrogen on synaptic pattern in the amygdala: implications for sexual differentiation of the brain , 1981, Brain Research.

[34]  H. Kraemer,et al.  How can we learn about developmental processes from cross-sectional studies, or can we? , 2000, The American journal of psychiatry.

[35]  Michael I. Miller,et al.  Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type , 2006, NeuroImage.

[36]  F. Bidlingmaier,et al.  Plasma Estrogens in Childhood and Puberty under Physiologic and Pathologic Conditions , 1973, Pediatric Research.

[37]  E Gould,et al.  Estrogen Stimulates a Transient Increase in the Number of New Neurons in the Dentate Gyrus of the Adult Female Rat , 1999, The Journal of Neuroscience.

[38]  M. Keshavan,et al.  Sex differences in brain maturation during childhood and adolescence. , 2001, Cerebral cortex.

[39]  Lucía Pronsato,et al.  Role of 17β-estradiol and testosterone in apoptosis , 2011, Steroids.

[40]  C. Woolley,et al.  Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  Rhoshel K. Lenroot,et al.  Sex differences in the adolescent brain , 2010, Brain and Cognition.

[42]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited—Again , 1995, NeuroImage.

[43]  Benjamin Thyreau,et al.  PyXNAT: XNAT in Python , 2012, Front. Neuroinform..

[44]  S. Blakemore,et al.  The role of puberty in the developing adolescent brain , 2010, Human brain mapping.

[45]  J. Rapoport,et al.  Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4–18 years , 1995, The Journal of comparative neurology.

[46]  C. Zahn-Waxler,et al.  Disorders of childhood and adolescence: gender and psychopathology. , 2008, Annual review of clinical psychology.

[47]  R. Kahn,et al.  Sex differences in the risk of schizophrenia: evidence from meta-analysis. , 2003, Archives of general psychiatry.

[48]  C. D. Fowler,et al.  Estrogen and adult neurogenesis in the amygdala and hypothalamus , 2008, Brain Research Reviews.

[49]  Polina Golland,et al.  Automated segmentation of hippocampal subfields from ultra‐high resolution in vivo MRI , 2009, Hippocampus.

[50]  Marisa O. Hollinshead,et al.  Identification of common variants associated with human hippocampal and intracranial volumes , 2012, Nature Genetics.

[51]  C. Sisk,et al.  The neural basis of puberty and adolescence , 2004, Nature Neuroscience.

[52]  A. Beltz,et al.  Sexual differentiation of human behavior: Effects of prenatal and pubertal organizational hormones , 2011, Frontiers in Neuroendocrinology.

[53]  Christos Davatzikos,et al.  Neuroimaging of the Philadelphia Neurodevelopmental Cohort , 2014, NeuroImage.

[54]  Alan C. Evans,et al.  Testosterone-related cortical maturation across childhood and adolescence. , 2012, Cerebral cortex.

[55]  S. DeKosky,et al.  Gonadal steroids influence axon sprouting in the hippocampal dentate gyrus: A sexually dimorphic response , 1986, Experimental Neurology.