Sex differences in brain and behavior in adolescence: Findings from the Philadelphia Neurodevelopmental Cohort

Abstract

Sex differences in brain and behavior were investigated across the lifespan. Parameters include neurobehavioral measures linkable to neuroanatomic and neurophysiologic indicators of brain structure and function. Sexual differentiation of behavior has been related to organizational factors during sensitive periods of development, with adolescence and puberty gaining increased attention. Adolescence is a critical developmental period where transition to adulthood is impacted by multiple factors that can enhance vulnerability to brain dysfunction. Here we highlight sex differences in neurobehavioral measures in adolescence that are linked to brain function. We summarize neuroimaging studies examining brain structure, connectivity and perfusion, underscoring the relationship to sex differences in behavioral measures and commenting on hormonal findings. We focus on relevant data from the Philadelphia Neurodevelopmental Cohort (PNC), a community-based sample of nearly 10,000 clinically and neurocognitively phenotyped youths age 8–21 of whom 1600 have received multimodal neuroimaging. These data indicate early and pervasive sexual differentiation in neurocognitive measures that is linkable to brain parameters. We conclude by describing possible clinical implications.

A three‐wave longitudinal study of subcortical–cortical resting‐state connectivity in adolescence: Testing age‐ and puberty‐related changes

“…That is, amygdala–hippocampus connectivity, a connection most prominently influenced by sex, was stronger for boys than for girls, and hippocampal–ventral ACC connectivity was stronger for girls than for boys. Previous research on sex differences has mostly been done in adults (e.g., Alarcón, Cservenka, Rudolph, Fair, & Nagel, ; Kogler et al, ), and has shown higher hippocampal and/or amygdala connectivity in females than males, possibly related to their better memory performance (Gur & Gur, ). The sex differences we observed here may be an interesting starting point, but should be interpreted with caution until replicated, given the lack of consistent findings in prior developmental samples.…”

Association between structural brain network efficiency and intelligence increases during adolescence

“…Girls enter puberty earlier than boys (Mul et al, ), and their brains also develop at a different pace during adolescence (Gogtay et al, ; Gur and Gur, ; Raznahan et al, ). Although puberty might in addition to age explain variance in brain development (Blanton et al, ; Brouwer et al, ; Menzies, Goddings, Whitaker, Blakemore, & Viner, ; review by Peper, Hulshoff Pol, Crone, & van Honk, ), we did not control for differences in pubertal timing.…”

Cross-sectional and longitudinal associations of family income-to-needs ratio with cortical and subcortical brain volume in adolescent boys and girls

“…Neural plasticity during adolescence is second only to infancy; this heightened plasticity may render the brain especially vulnerable to variation in environmental input during adolescence (Gee & Casey, 2015). Conceptualizing adolescence as an "organizational" period for the brain (Gur & Gur, 2016), researchers have posited that neurodevelopment during adolescence underlies the acquisition of complex skills involving executive function that are important for wellbeing in adulthood (Aoki, Romeo, & Smith, 2017). Given the sensitivity of the adolescent brain and the potentially cascading consequences of deviations in neurodevelopment, it is important to characterize more precisely the associations between SES and brain volume during this period.…”

“…Although studies of the neural correlates of SES typically "control" statistically for the biological sex of participants (i.e., by holding sex constant in predictive models), researchers rarely test sex as a moderator of SES and brain structure. The confluence of sex differences in neurodevelopment (Dennison et al, 2013;Gur & Gur, 2016;Wierenga, Langen, Oranje, & Durston, 2014;Wierenga, Sexton, Laake, Giedd, & Tamnes, 2018) and in sensitivity to environmental input Jaffee, Caspi, Moffitt, Polo-Tomás, & Taylor, 2007;Whittle et al, 2014Whittle et al, , 2017 may lead to sex differences in the corresponding to family size. Given wide variation in cost of living across the United States, the same income in different geographic areas may not reflect equivalent economic wellbeing.…”

“…associations of SES with brain structure. For example, the effects of environmental input are likely to depend on the nature of ongoing neurodevelopmental processes (Bock, Wainstock, Braun, & Segal, 2015), which are sexually dimorphic (i.e., whereas some regions develop faster in boys, others develop faster in girls; [Dennison et al, 2013;Gur & Gur, 2016;Wierenga et al, 2014]). Importantly, there is growing evidence that environmental input, including variation in SES, has sex-specific effects on brain structure.…”