Adolescent maturation of the prefrontal cortex: Role of stress and sex in shaping adult risk for compromise

Abstract

Adolescence is a highly dynamic period of development, which includes the final organizational phases of neural maturation within the prefrontal cortex (PFC). The organizational events of neural pruning and myelination occur in a sex‐specific manner, potentially giving rise to the disparities in mood disorders in adulthood. Because of the extended developmental time period of the PFC, environmental insults, including psychosocial stressors, may play a major role in steering the maturation of this region. In this review, the literature surrounding the sex specific alterations that occur in the PFC in rodent models following adolescent stress will be discussed. This will be complimented by a brief review on the state of human research in PFC sex differences in the development of white matter and cytoarchitecture across the lifespan. Taken together, the impact of developmental psychosocial stress on the circuitry of the PFC and resulting adult phenotypes will be summarized with a focus on the importance of considering sex differences in order to build a better understanding of developmental influences on adult disorders.

Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice

“…A wealth of observations in animals ( Brenhouse and Andersen, 2011 ; Shaw et al, 2020b ) and humans ( Eid et al, 2019 ) show that females are more vulnerable than male to develop stress-related disorders, such as major depression and anxiety. Here, we found important sex-dependent differences following peripubertal stress; in fact, most effects were only observed in diestrus females or when considering both sexes together, but rarely only in males.…”

“…The impact of stressful events is especially important during early life, when certain cortical regions, specially the prefrontal cortex (PFC), are still developing ( Shaw et al, 2020a ). Late stages of neural development extend well into adolescence (in mice from postnatal day (P) 28 until P42 ( Spear, 2000 ; Rice and Barone, 2000 ), herewith termed peripubertal period).…”

Sex differences in the neurochemistry of frontal cortex: Impact of early life stress

“…However, most of the differences described to date are structural (e.g. gray and white matter volume differences between male and female humans, Gennatas et al., 2017; Lenroot & Giedd, 2010; Shaw et al., 2019; Szeszko et al., 2003), and potential sex differences in neurochemistry are poorly understood. Neurochemical information is particularly crucial because the vast majority of standard treatments for mental disorders rely on pharmacotherapy that aims to address potential neurochemical imbalances (Bortolasci et al., 2018; World Health Organization, 2001).…”

“…The frontal cortex matures slower than other brain regions in humans and rodents (Case y & Jones, 2010; Drzewiecki et al., 2020; Ganella, et al., 2018; Paus & Giedd, 2008; Shaw et al., 2008; Steinberg, 2008; Zbukvic & Kim, 2018), and it is particularly susceptible to experience‐dependent changes, again in humans and in rodents (Charlton et al., 2019; Eiland & Romeo, 2013; Gee et al., 2013; Guerin et al., 2019; Shaw et al., 2019). Indeed, many mental disorders have been linked to frontal cortex dysfunction following stress early in life (Casey & Jones, 2010; Gee et al., 2018; Paus & Giedd, 2008; Shaw et al., 2019). Notably, the rate of frontal cortex development is sex‐dependent, with earlier maturation apparent in females compared to males (Cullity et al., 2019; Gennatas et al., 2017).…”

Sex differences in mechanisms of disease

“…Two reviews on this topic lead the issue. First, Shaw et al examine one of the most stress‐sensitive developmental periods, adolescence. They focus on the prefrontal cortex, which continues to mature throughout adolescence, undergoing critical windows of structural plasticity in both gray and white matter.…”