Stress and the developing adolescent brain

Abstract

Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes coincident with adolescence. An emerging line of research has indicated that stressors experienced during this crucial developmental stage may affect the trajectory of this neural maturation and contribute to the increase in psychological morbidities, such as anxiety and depression, often observed during adolescence. In this review, we discuss the short- and long-term effects of periadolescent stress exposure on the structure and function of the brain. More specifically, we examine how stress at prepubertal and early adolescent stages of development affects the morphological plasticity of limbic and cortical brain regions, as well as the enduring effects of adolescent stress exposure on these brain regions in adulthood. We suggest that, due to a number of converging factors during this period of maturation, the adolescent brain may be particularly sensitive to stress-induced neurobehavioral dysfunctions with important consequences on an individual's immediate and long-term health and well-being.

Keywords: ACTH; CA1; CMS; CRS; CVS; DG; GR; HPA; HPA axis; LR; MPN; MR; N-methyl-D-aspartate; NMDA; OFC; SEM; SP-MF; TSST-C; Trier Social Stress Test for Children; adolescence; adrenocorticotropin hormone; chronic mild stress; chronic restraint stress; chronic variable stress; cornu ammonis 1; dentate gyrus; glucocorticoid receptor; hypothalamic–pituitary–adrenal; low responder; mPFC; medial prefrontal cortex; medial preoptic nucleus; mineralocorticoid receptor; orbitofrontal cortex; puberty; standard error of the mean; stress; supra-pyramidal mossy fiber terminal fields.

Figure 1

Time lines of development in rodents (e.g., rats and mice, A) and humans (B) along with approximate age ranges and commonly used terms for referring to those stages of development. Abbreviations: d, day; wk, week; yr, year.

Figure 2

Mean (± SEM) plasma corticosterone in prepubertal (30 days old) and adult (70 days old) male rats before, during, or after a single 30 min session of restraint stress (left panel) or 30 min sessions of restraint administered daily for eight days (right panel). Asterisks indicate a significant difference between prepubertal and adult animals at that time point. Adapted from (Lui et al., in press).

Figure 3

Representative tracings and data plots for the effects of chronic restraint stress (CRS) during adolescence on apical dendritic remodeling in both males and females in the CA3 region of the hippocampus (A), the medial prefrontal cortex prelimbic region (B), and basolateral amygdala (C). Asterisks indicate a significant difference between CRS and control animals. Note dendritic atrophy in the hippocampus and prefrontal cortex, but dendritic hypertrophy in the amygdala. Adapted from (Eiland et al., 2012).