Elsevier

Psychoneuroendocrinology

Volume 81, July 2017, Pages 70-79
Psychoneuroendocrinology

Longitudinal changes in pubertal maturation and white matter microstructure

https://doi.org/10.1016/j.psyneuen.2017.03.017Get rights and content

Highlights

  • Result showed increases in FA with age and higher FA in boys versus girls.

  • Physical pubertal development contributes to changes in FA.

  • Sex-specific patterns seen between changes in physical puberty and FA.

Abstract

Emerging evidence in the field of adolescent neurodevelopment suggests that pubertal processes may contribute to known trajectories of brain maturation, and may contribute, in part, to sex differences in related cognitive, behavioral and mental health outcomes. The current longitudinal study examined how changes in physical pubertal maturation (measured by the Peterson Developmental Scale) predict changes in white matter microstructure in 18 boys and 15 girls over an approximate 2-year follow-up period, while accounting for age. Using Tract-Based Spatial Statistics and multi-level modeling, the results showed that physical pubertal changes predict patterns of changes in fractional anisotropy (FA) in white matter regions in the thalamus, precentral gyrus, superior corona radiata, corpus callosum (genu), superior corona radiata, and superior frontal gyrus. Sex specific changes were also seen, as changes in gonadal and adrenal development related to increases in FA in the superior frontal gyrus and precentral gyrus in boys, but gonadal development related to decreases in FA in the anterior corona radiata in girls. These findings are the first to show how changes over time in pubertal development influence white matter development. In addition, they support a larger body of emerging research suggesting that pubertal processes contribute to distinct changes in boys and girls across brain development.

Introduction

Adolescence is a unique period of brain development, where changes in brain structure and function are coupled with improvements in cognitive domains important for adult-like functioning. White matter volumes continue to increase with age across adolescence. Child and adolescent neuroimaging studies using longitudinal diffusion tensor imaging (DTI) consistently show decreases in mean diffusivity (MD) with age, as well as increases in fractional anisotropy (FA) and decreases in radial diffusivity (RD) (Giorgio et al., 2010, Bava et al., 2011, Lebel and Beaulieu, 2011, Wang et al., 2012, Simmonds et al., 2014). A number of sex differences have also been reported in white matter microstructure (Schmithorst et al., 2008, Herting et al., 2012, Wang et al., 2012, Simmonds et al., 2014, Seunarine et al., 2016), suggesting that patterns of white matter development differ between boys and girls as they mature through late childhood and adolescence in a region- and time- specific manner. These white matter changes are thought to reflect a combination of increased axonal diameter and continued myelination (Paus, 2010). Maturation of white matter is thought to play a vital role in communication between various regions throughout the brain, which may allow for improved signal transduction. Further, white matter maturation likely impacts the concurrent development of cognitive, emotional, behavioral and motor outcomes. Further understanding of major factors influencing white matter maturation is needed to improve our understanding of individual differences in risk for emotional and behavioral problems that begin to emerge during the teenage years (Ladouceur et al., 2012). While much has been learned, most existing research has examined white matter development as a function of chronological age. We aimed to address this gap in knowledge by exploring longitudinal changes in white matter as a function of puberty compared to chronological age.

Beyond chronological age, both animal and human studies have shown that pubertal maturation exerts sex-specific effects on brain structure (for review see (Juraska et al., 2013)). A few cross-sectional studies have examined how puberty may contribute to the sex differences in white matter microstructure development seen across adolescence. Asato et al. (2010) examined puberty in children (8–12 years), adolescents (13–17 years), and adults (18–28 years) using DTI. In all but one white matter region of interest, maturation seemed incomplete for individuals in mid-puberty, but were adult-like for those with completed pubertal maturation (i.e. post-pubertal stage). Using physical markers of pubertal development as a continuous variable, puberty has also been shown to relate to higher FA values in a sex-specific manner in superior frontal white matter regions (Herting et al., 2012). In the same study, testosterone levels were found to positively predict FA in regions where boys had higher FA compared to girls, whereas estradiol was found to show a negative relationship with FA in girls (Herting et al., 2012). However, a separate study found pubertal stage and testosterone related to MD, but not FA, in various white matter regions in boys, while DHEA and estradiol did not relate to DTI outcome measures (Menzies et al., 2015). Collectively, these cross-sectional studies show that pubertal maturation relates to white matter microstructure in a sex-specific manner. However, it remains unclear how within-subject changes in pubertal development may influence changes in white matter microstructure across adolescence in boys and girls.

The current longitudinal DTI study aimed to replicate known age-related changes in white matter across adolescence, as well as expand the existing literature by examining how changes in pubertal development influence changes in white matter development across adolescence. We examined how changes in adrenal- and gonadal- related pubertal markers influence changes in white matter diffusivity in boys and girls (FA, as well as MD, RD and axial diffusivity (AD)). Given previously reported sex differences (Asato et al., 2010, Herting et al., 2012, Simmonds et al., 2014), we expected to replicate widespread age-related changes in white matter microstructure across adolescence, and for boys to show larger increases in FA as compared to girls. Furthermore, we expected that changes in pubertal development would predict changes in white matter development, after accounting for age, and in a sex-specific manner.

Section snippets

Participants

The current longitudinal study design included adolescents between the ages of 10 and 18 years of age at the time of their first MRI visit (Time 1) and were asked to participate in a follow-up visit (Time 2) approximately 2 years later (Fig. 1A). Participants were recruited via fliers, advertisements, and online postings. Written assent and consent were obtained from all participants and their parent or legal guardian, according to procedures outlined by the Institutional Review Board of

Sample characteristics

Four subjects were removed due to unusable data at one or more timepoints, whereas 10 individuals had only one (out of 2 possible) DTI runs at one of the two timepoints. The final sample included 19 boys and 25 girls for age analyses. Demographics for the final samples included 36% Caucasian, 30% African American/Black, 21% more than 1 race, 2% Native Hawaiian or other, and 11% chose not to disclose, with 50% Hispanic. The sample came from households with various income levels ($5000–9999:

Discussion

The present study was the first to examine how longitudinal changes in different aspects of puberty-related markers of physical development predicted changes in white matter microstructure in adolescents. Neurodevelopment has primarily been studied in the context of age. Beyond replicating age and sex effects in white matter microstructure, we show that pubertal-markers contribute to these changes across adolescence after accounting for age-related change. The results suggest that changes in

Conclusions

The current study examined how within-subject changes in physical markers of pubertal development influence changes in white matter microstructure. The results show that both adrenal- and gonadal-based pubertal changes predict unique changes in FA. Furthermore, the results suggest that adrenal and gonadal-based changes lead to increases in FA in boys, but decreases in FA in girls, in frontal (precentral and superior frontal gyrus) as well as anterior and posterior corona radiata white matter

Conflicts of interest

None.

Funding

Financial support was provided by the National Institutes of Health under award numbers: R01MH087563 (Sowell), F32HD078084 (Herting), and F32AA022561 (Uban). The funding sources had no involvement in study design; data collection, analysis, and interpretation; writing the report; or the decision to submit the article for publication.

Acknowledgements

We would like to thank Alexy Andrade, Max Orozco, Kirsten Lynch, Tatevik Abaryan, and Genevieve Rodriguez for helping with data collection, as well as Alexy Andrade for scoring and analytic support.

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