Pubertal status in early adolescence predicts changes in cortical grey matter structure over time

New neuroimaging research sheds light on the relationship between pubertal development and brain maturation in early adolescence. According to the research, which was published in Developmental Cognitive Neuroscience, the stage of puberty can predict how the grey matter of the brain changes over time. These changes may have implications for brain function and development during adolescence.

The researchers behind the new study aimed to provide more comprehensive understanding of the relationship between pubertal development and brain maturation by conducting a large-scale longitudinal study using advanced statistical techniques and controlling for various factors.

They noted that previous studies on the association between pubertal development and brain maturation had limitations, including small sample sizes, cross-sectional designs (which only provide a snapshot at a single point in time), and inconclusive findings about the directionality of effects and sex differences.

“I study the adolescent brain and when I came across the subject of puberty I was quite intrigued by research that showed that puberty has been advancing in the last few decades, especially in girls, potentially having an average age of 15-16 in the 1800s and now it seems to be 12-13, which has probably been the stable average since the 1950s-70s or so,” explained study author Dani Beck (@_DaniBeck), a neuroimaging researcher affiliated with the University of Oslo, the Norwegian Centre for Mental Disorders Research, and Diakonhjemmet Hospital.

He was also intrigued by the fact that the timing of puberty varies among individuals. “Some individuals may enter puberty at age 9, while others at age 13 or 14, and there is some evidence showing that although this variance is largely genetic (50-80% heritability for both males and females), there are also a wide range of environmental factors that influence pubertal onset, and that these are important to investigate in terms of their impact on the brain and mental health,” Beck explained.

Some factors that contribute to earlier puberty include socioeconomic status, obesity, and nutrition. Studies show that children growing up in more challenging environments tend to experience puberty earlier, he continued.

“There is no definitive or conclusive answer for this that the field has accepted as fact as a whole, but one popular theory that stems from sociology is the theory of adultification (there is also the stress acceleration hypothesis which is similar), and that these kids may be forced to adapt to harsher environments quicker by undergoing puberty earlier (either to ensure likelihood of reproductive success in a threatening environment or ‘adultify’ quicker to adapt to their environment). This is another thing I found to be fascinating, especially because it can have an influence on the development of the brain and potentially negative consequences for child mental health or risk of future mental health problems.”

To conduct the study, the researchers used data from the Adolescent Brain Cognitive Development (ABCD) Study, which is a large-scale longitudinal study of children and adolescents aged 9-14 years. They analyzed brain imaging data, specifically measures of grey matter volume, cortical thickness, surface area, and white matter microstructure, obtained through magnetic resonance imaging (MRI). They also assessed pubertal development using the Pubertal Development Scale (PDS), which measures the perceived development of secondary sex characteristics.

The study included a large sample of participants (8,896 at baseline and 6,099 at follow-up) and accounted for various factors such as socioeconomic status, body-mass index, and genetic ancestry-derived ethnicity. The researchers also addressed potential confounding effects by harmonizing data from multiple MRI scanners used across different study sites.

Both males and females demonstrated a connection between pubertal development and changes in the surface area of the brain (the total area of the outer surface of the brain). This means that as individuals went through puberty, their brain’s surface area underwent alterations.

Males who were more developed in terms of puberty at the beginning of the study showed less increase in surface area compared to those who were less developed. In other words, the more advanced the pubertal development, the less the surface area of the brain increased over time for males. This finding was unexpected, as previous research had reported decreases in surface area associated with more developed males.

Similarly, females also showed a relationship between pubertal development and changes in brain surface area, but the association was even stronger in females compared to males.

The study also used diffusion tensor imaging (DTI) to investigate the connections between pubertal development and the brain’s white matter structure. The researchers found that changes over time in pubertal development were related to changes in fractional anisotropy, which is a measure of the organization of white matter fibers, for both males and females.

For females, the study also found that the initial level of pubertal development predicted changes in cortical thickness over time. However, this association was not observed in males.

The findings suggest that the stage of puberty a person is in can predict the maturation of the cerebral cortex, which is the outer layer of the brain. However, the strength of these associations varies between males and females.

“The brain and the body co-exist and many of the things that influence our bodies, including physical changes throughout childhood and adolescence, also impact our brains. From our findings and other studies in the field, the data suggests that pubertal development and brain development are related, and the changes in one influences the changes in the other and vice versa.”

“But the most interesting finding of our paper is, is that puberty status seems to predict changes in the brain (at least cortical maturation/gray matter), not vice versa. Many that study hormones in the brain would disagree with this, as puberty is also a process that happens or starts in the brain in many ways, with hormones and changes potentially starting there, rather than puberty just being about sexual developmental or observable physical changes. In the end, more research needs to be done to further investigate this directionality. We definitely can’t claim the chicken came before the egg based on our findings alone.”

Beck said that he and his colleagues were surprised to find that there weren’t many connections between puberty and brain measures when they analyzed data from a single point in time, except for a link between puberty and cortical surface area in boys. It wasn’t until they examined changes that occurred over time that they found more significant results.

The researchers also acknowledged some limitations, such as the limited age range of the participants and the need for longitudinal data that spans the entire pubertal period to fully understand sex-specific developmental patterns.

“The participants also were recruited from age 9 and are in the oldest in this study 14 years old, which means the early gonadal processes for many kids are not captured in the data. Additionally, at this age range, not many of the boys actually have through much of the pubertal process, with many still in the early stages, while the girls progressed from early to mid- and even late pubertal development.”

“We used a longitudinal design which is very good in terms of design, but ideally we want to look at the entire process of puberty in these participants (in a wider age range) and follow them until early adulthood with 4-6 timepoints instead of 2. This would help us model change much better and be more confident in our results. And lastly, we only looked at puberty in terms of a parent filled questionnaire called the PDS, and ideally you would want to combine hormone measures as well to get a better validated overview of pubertal status.”

The researchers emphasize that adolescence is a critical period for brain development and that accelerated pubertal development may be a concern for the developing brain. Earlier pubertal timing has been linked to several negative psychological outcomes.

“The important thing about puberty and brain relations is probably their relation to mental health and risk of things like depression and anxiety in our youth, and this study did not have space to examine these things. So I think it would be nice to stress that this study establishes and replicates some important work in the field of puberty, and does a great job at investigating brain-puberty relations in such a large sample of children with longitudinal data! But the hope is for future research to follow it up by looking at psychopathology.”

“Another big interest which I touched on above is that there are small influences of the environment as being a contributing factor for earlier pubertal development, and if that is a reason the children are going through puberty earlier, and this has an effect on the brain developing quicker, and this in turn has an impact of increasing risk of depression and anxiety, then 1) we need more research that confirms this, 2) maybe we need to invest in intervention strategies that target increasing equity in communities and making sure children have some protective factors in schools and their communities which may help improve the environments they grow up in.”

The study, “Puberty differentially predicts brain maturation in male and female youth: A longitudinal ABCD Study“, was authored by Dani Beck, Lia Ferschmann, Niamh MacSweeney, Linn B. Norbom, Thea Wiker, Eira Aksnes, Valerie Karl, Fanny Dégeilh, Madelene Holm, Kathryn L. Mills, Ole A. Andreassen, Ingrid Agartz, Lars T. Westlye, Tilmann von Soest, and Christian K. Tamnes.

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