Poster No:
2147
Submission Type:
Abstract Submission
Authors:
Shau-Ming Wei1, Isabel Wilder2, Shane Kippenhan3, Michael Gregory1, Christina Recto2, Destiny Wright2, Caroline Raymond2, Lynnette Nieman4, Peter Schmidt1, Karen Berman5
Institutions:
1NIMH, Bethesda, MD, 2NIMH/NIH, Bethesda, MD, 3NIH, Bethesda, MD, 4NIDDK/NIH, Bethesda, MD, 5NIMH, National Institutes of Health, Bethesda, MD
First Author:
Co-Author(s):
Karen Berman
NIMH, National Institutes of Health
Bethesda, MD
Introduction:
Puberty is a period of marked changes in behavior, emotion, and cognition (1-3). Well-documented sex differences in the brain also emerge during this critical developmental period (4,5). The hippocampus is reported to undergo substantial structural and functional changes during puberty, and basic science studies have demonstrated that puberty-related sex hormone secretion influences hippocampal morphology (6,7). While some studies in humans have documented both the emergence of sex differences (8) and sex-hormone related changes (9,10) in hippocampal structure during puberty, these findings have been complicated by confounding variables (such as age, menstrual cycle status), cross-sectional designs, or temporally sparse sampling of longitudinal data during a period when neurodevelopmental changes may be occurring rapidly. Here, we employed data from the ongoing "NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty" to document developmental trajectories of hippocampal volume and estradiol (E2) and testosterone (T) serum levels in healthy boys and girls from prepuberty to age 18 to identify associated patterns of change.
Methods:
Healthy children between the ages of 8 (when they were ascertained by clinicians to be pre-pubertal) and 18 years were studied every 9 months with neuroimaging and hormonal measurements. Fasting morning blood samples to measure E2 and T levels and 3T structural MRI scans (GE MR750 scanner, sagittal acquisition, 1mm isotropic voxels; TE=1.8ms; TR=10.5ms) were collected across 566 cumulative visits of 135 healthy children (56 girls). To control for menstrual cycle-related hormonal effects, structural scans from menarchal girls were collected during the follicular phase (days 4-11 of the menstrual cycle) as confirmed by serum progesterone levels <2 ng/ml. Repeated measures correlations (R's rmcorr package) and longitudinal mixed-effects spline models (R's gamm4 package) were used to identify associations across age between estradiol and testosterone levels and Freesurfer-derived whole hippocampal volume.
Results:
Serum E2 and T levels positively correlated with left and right hippocampal volumes in both sexes separately, regardless of age (p's<0.0006, r's>0.22). Mixed-effects spline-modeling of developmental relationships between hormones and hippocampal volumes showed significant age-by-T interactions for left hippocampus and age-by-E2 interactions bilaterally. Hippocampal volumes increased faster as estradiol levels increased (p's<0.001), and a similar relationship was found with testosterone for the left hippocampus, where hippocampal volume increased faster with increasing testosterone (p=0.02).
Conclusions:
Our longitudinal findings empirically document E2- and T-dependent hippocampal structural changes across puberty. The specific observation that higher gonadal hormone levels are associated with faster age-related increases of bilateral hippocampal volume suggests that the rapidity of the pubertal transition could have significant developmental impact on long-term hippocampal morphology and function and reinforces the importance of temporally high-density investigation. Finally, these changes in hippocampal volume related to variations in gonadal hormone levels during puberty may have important implications for understanding the emergence of sex differences and increases in vulnerability to neuropsychiatric disorders that are well documented during this period.
Lifespan Development:
Normal Brain Development: Fetus to Adolescence
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Normal Development 1
Subcortical Structures 2
Keywords:
Development
STRUCTURAL MRI
Structures
Other - sex hormones
1|2Indicates the priority used for review
Provide references using author date format
1. Somerville LH, Casey BJ. (2010) Developmental neurobiology of cognitive control and motivational systems. Curr Opin Neurobiol. 20:236–241.
2. Luna B. (2009) Developmental changes in cognitive control through adolescence. Adv Child Dev Behav. 37:233–278.
3. Casey BJ, Jones RM, Hare TA. (2008) The Adolescent Brain. Ann N Y Acad Sci. 1124:111–126.
4. Blakemore S-J, Burnett S, Dahl RE. (2010) The role of puberty in the developing adolescent brain. Hum Brain Mapp. 31:926–933.
5. Giedd JN, Clasen LS, Lenroot R, et al. (2006) Puberty-related influences on brain development. Mol Cell Endocrinol. 254–255. 154–162.
6. Cooke BM, Woolley CS. (2005) Gonadal hormone modulation of dendrites in the mammalian CNS. J Neurobiol. 64:34–46.
7. Gould E, Woolley CS, Frankfurt M, McEwen BS. (1990) Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci. 10:1286–1291.
8. Satterthwaite TD, Vandekar S, Wolf DH, Ruparel K, et al. (2014) Sex differences in the effect of puberty on hippocampal morphology. J Am Acad Child Adolesc Psychiatry. Mar;53(3):341-50.
9. Herting, M.M., Gautam, P., Spielberg, J.M., Kan, E., et al. (2014) The role of testosterone and estradiol in brain volume changes across adolescence: A longitudinal structural MRI study. Hum. Brain Mapp. 35: 5633-5645.
10. Vijayakumar N, Youssef G, Allen NB, Vicki Anderson V, et al. (2021) The effects of puberty and its hormones on subcortical brain development. Comprehensive Psychoneuroendocrinology 7:100074