Stress in an Adolescent's Family Decreases the Hormones of Puberty.

Curr Dir Psychol Sci. Author manuscript; available in PMC 2014 Dec 23.

Published in final edited form as:

PMCID: PMC4274618

NIHMSID: NIHMS627920

The Teenage Brain: The Stress Response and the Adolescent Brain

Russell D. Romeo

Department of Psychology and Neuroscience and Behavior Program, Barnard Higher of Columbia University, New York, NY 10027

Abstract

Adolescence is a fourth dimension of many psychosocial and physiological changes. 1 such change is how an individual responds to stressors. Specifically, adolescence is marked by significant shifts in hypothalamic-pituitary-adrenal (HPA) axis reactivity, resulting in heightened stress-induced hormonal responses. It is before long unclear what mediates these changes in stress reactivity and what impacts they may have on an adolescent individual. Nevertheless, stress-sensitive limbic and cortical encephalon areas that continue to mature during adolescence may be particularly vulnerable to these shifts in responsiveness. Consequently, perturbations of the maturing adolescent encephalon may contribute to the increment in stress-related psychological dysfunctions, such every bit anxiety, low, and drug abuse, oftentimes observed during this stage of development. The purpose of this review is to depict the changes that occur in HPA function during adolescence, too as briefly talk over the possible ramifications of these changes on the developing brain and psychological wellness.

Keywords: Boyhood, Hypothalamic-Pituitary-Adrenal Axis, Puberty, Stress

Stress happens. It's a fact of life. Nevertheless, the blazon of stressors nosotros feel and how we respond to them modify throughout our life. Adolescence represents a stage in development when both of these aspects of stress are in flux. Though most of united states of america appreciate that the nature of stressors change during adolescence, less appreciated are the unique ways in which adolescent individuals respond to stress. This review will focus on the substantial shifts in stress reactivity exhibited during adolescence, especially in the context of hormonal responsiveness. Information technology will also hash out the potential impact of these hormonal changes on the developing boyish encephalon. The research described in this review will largely highlight the work conducted on basic fauna models, as it is from these models that most of our mechanistic understanding of historic period-dependent changes in stress reactivity and neurobiological function are derived.

The Stress Response

When an private experiences a stressor, be information technology physical or psychological, ii hormonal systems are activated to help the private cope with the situation. The first is mediated by the rapid actions of the sympathetic nervous system, leading to the release of epinephrine and norepinephrine into the blood stream. It is this immediate response that mediates the transient so chosen "fight-or-flight" reaction to stress. The second is a slower, more protracted hormonal response mediated by the hypothalamic-pituitary-adrenal (HPA) centrality. This response is initiated by a group of neurons in the paraventricular nucleus of the hypothalamus (PVN), which secrete corticotropin-releasing hormone (CRH) to point the pituitary to release adrenocorticotropic hormone (ACTH). ACTH, in plow, stimulates the adrenal glands to synthesize and secrete the glucocorticoids (i.east., cortisol in humans and corticosterone in many rodent species). Once the stressor has concluded, the glucocorticoids human action though negative feedback on the pituitary gland and a variety of forebrain regions, namely the hypothalamus, hippocampus, and prefrontal cortex, ultimately terminating the response past reducing the farther production and release of CRH and ACTH (Herman et al., 2003; Effigy 1). Thus, in the context of the HPA reaction to stress, the brain is both the initiator and a major target of the glucocorticoid response.

A simplified schematic of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis as well as the negative feedback that allows the HPA axis to recover back to baseline following termination of a stressor. Abbreviation: adrenal gland (AD), adrenocorticotropin hormone (ACTH), anterior pituitary (AP), corticosterone (CORT), corticotropin-releasing hormone (CRH), negative feedback (−), positive drive (+).

The glucocorticoids are responsible for many of the adaptive physiological and behavioral responses to stressors, such as mobilizing energy stores, enhancing immune reactions, and increasing learning and memory abilities. However, chronic or more than prolonged exposure to these hormones can result in numerous maladaptive outcomes, including metabolic disorders and impaired immune and cognitive functions. Thus, factors that regulate HPA reactivity and the dynamics of the hormonal stress response can have important short- and long-term consequences on an individual's physiology and behavior (McEwen, 1998).

Adolescent Development of the Hormonal Stress Response

Although adolescence is marked by many neuroendocrine changes, the shifts in HPA function are more subtle than the relatively conspicuous increases in gonadal hormones associated with puberty. That is, though basal ACTH and glucocorticoid levels remain fairly stable throughout adolescence, it is the amount and duration of these hormones released in times of stress that show notable changes. Numerous studies in both male and female rats, for example, betoken that animals on the cusp of adolescence (i.eastward., ~30 days of age) show significantly protracted ACTH and corticosterone responses compared to adults (i.e., > 65 days of historic period) following a brief exposures to a variety of stressors (e.1000., foot shock, hypoxia, restraint; Goldman, Winget, Hollingshead, & Levine, 1973; Romeo, Lee, Chhua, McPherson, & McEwen, 2004; Romeo, Lee, & McEwen, 2004; Vazquez & Akil, 1993). Specifically, these hormonal stress responses tin can last 45–60 min longer in animals prior to adolescent maturation (Romeo, 2010a, 2010b; Figure 2). These extended hormonal responses in per-adolescent animals are different than those of neonatal pre-weanling rats (i.e., prior to 21 days of age), which usually demonstrate hypo-responsiveness to stressors (Sapolsky & Meaney, 1986). Interestingly, these prolonged ACTH and corticosterone responses post-obit stress practice non but gradually assume their adult-similar patterns as puberty and adolescence progress, only instead show relatively more abrupt shifts, with stress-induced ACTH responses maturing later on (i.e., between 50–sixty days of historic period) than corticosterone responses (i.e., betwixt 30–40 days of age; Foilb, Lui, & Romeo, 2011; Figure three). These data indicate that each node along the HPA centrality may have its ain developmental trajectory during boyhood. It is important to note that recent studies in human adolescents have besides reported changes in hormonal responsiveness, though not exactly paralleling the rodent studies. More specifically, boys and girls in later on stages of adolescence (15–17 years old) displaying greater stress-induced cortisol levels compared to individuals in tardily childhood or earlier stages of adolescence (9–xiii years onetime; Gunnar, Wewerka, Frenn, Long, & Griggs, 2009; Stroud et al., 2009).

Mean (± SEM) plasma adrenocorticotropin hormone (ACTH) and corticosterone levels in pre-adolescent (28 days of historic period) and adult (77days of historic period) male rats before, during, and after a 30 min session of restraint stress (blackness bar under x-axis). Asterisks signal a significant deviation between the ages at that time signal. Adapted from (Romeo, Lee, Chhua, et al., 2004).

Mean (± SEM) plasma adrenocorticotropin hormone (ACTH) and corticosterone levels throughout pubertal and boyish development in xxx-, 40-, 50-, sixty-, and lxx-day one-time male rats before, during, and later a 30 min session of restraint stress (blackness bar under x-axis). In the upper panel, asterisks indicate significant differences from the 60- and 70-day old rats at that time point. In the lower panel, "#" indicates that 30-day old rats were significantly unlike from all other ages at that time point. Adapted from (Foilb et al., 2011).

Contributing Factors that Mediate the Adolescent Changes in Stress Reactivity

The mechanisms that mediate these adolescent-related changes in hormonal responsiveness remain unclear. However, it appears to involve both the activation and feedback phases of the HPA response. In the context of activation, experiments have shown that neural activity in the PVN, particularly in the CRH-containing cells, is higher in adolescent than adult animals following stress (Romeo et al., 2006; Viau, Bingham, Davis, Lee, & Wong, 2005). These data suggest that the prolonged ACTH and corticosterone responses prior to puberty may in part be driven past greater stress-induced CRH production and release. Along with these differences in activation, studies on negative feedback have shown that pre-treatment with the synthetic glucocorticoid, dexamethasone is less effective at blunting a stress-induced corticosterone response in prepubertal compared to developed rats (Goldman et al., 1973). Thus, these results would support the notion that periadolescent animals may show less glucocorticoid-dependent negative feedback on the HPA centrality than adults. Future studies volition need to address what cellular mechanisms mediate these putative age-dependent changes in sensitivity to negative feedback, such as differences in glucocorticoid receptor function in the encephalon and pituitary. To date, however, these avenues of research have been largely unexplored.

Another factor known to significantly modulate hormonal stress reactivity in adult man and non-human animals is gonadal hormones (Viau, 2002). In males, testosterone tends to reduce hormonal stress responsiveness, while in females estradiol often enhances stress reactivity (Viau, 2002). It is possible, therefore, that the substantial departure in gonadal hormones experienced by animals before and later puberty account for the changes in stress reactivity. However, not-man animate being studies that have experimentally manipulated gonadal hormone levels through surgery and/or hormone replacement have shown that prepubertal animals continue to bear witness greater stress-induced ACTH and corticosterone responses compared to adults (Romeo, Lee, Chhua, et al., 2004; Romeo, Lee, & McEwen, 2004). These results suggest, therefore, that elementary differences in gonadal hormone levels before and after puberty are non responsible for these adolescent-related changes in HPA stress responsiveness.

The Interaction of Boyhood and Stress History on Hormonal Responsiveness

Like to age, previous experience with stressors can besides shape one's hormonal stress responsiveness (Grissom & Bhatnagar, 2009). For example, an adult animal repeatedly exposed to the aforementioned stressor (homotypic stress) displays a habituated hormonal response compared to an adult exposed to that stressor for the showtime time. On the other hand, if an animal experiences the same stressor over and over again and is so hit with a novel stressor (heterotypic stress), a sensitized hormonal response is exhibited above that evoked by the novel stressor alone. These feel-dependent changes in HPA reactivity are different before and after adolescent development. In particular, homotypic stress leads to habituation in adults, only not in pre-boyish males (Lui et al., in press), while heterotypic stress leads to a similar peak response at both ages, just a slower recovery in animals prior to adolescence (Lui et al., in press; Figure four). It is currently unknown at what time during boyhood evolution these responses to homotypic and heterotypic stressors assume their adult-like patterns.

Mean (± SEM) plasma corticosterone levels in pre-boyish (30 days of age) and developed (77days of age) male person rats before, during, and later a 30 min session of restraint stress (black bar nether ten-axis) post-obit astute, homotypic, or heterotypic stress paradigms. Astute stress consisted of a single 30 min session of restraint stress, homotypic stress a daily 30 min session of restraint stress for 8 consecutive days, and heterotypic stress a daily 30 min session of cold room exposure (at 4°C) for seven consecutive days followed by 30 min of restraint on the eight^th day. Asterisks indicate a significant difference between the ages at that time indicate. Adjusted from (Lui et al., in printing).

The mechanisms responsible for this historic period- and experience-dependent plasticity in HPA reactivity are unclear. Though the contribution of negative feedback to these feel-dependent changes has not yet been explored, recent evidence suggests that differential activation of the PVN may be involved. That is, like to the greater activation of PVN neurons in adolescent animals following acute stress (Romeo et al., 2006), boyish animals also demonstrate higher PVN activation after both homotypic and heterotypic stress compared to adults, suggesting greater stress-induced hypothalamic bulldoze to the pituitary prior to machismo (Lui et al., in press). In addition to neurobiological substrates mediating these shifts in reactivity, peripheral factors may also play a role. For example, it is possible that the boyish pituitary and adrenal glands are more sensitive to CRH and ACTH, respectively, than they are in adulthood, thus in part potentially contributing to their greater responsiveness during adolescence. Regardless of the mechanisms that mediate these historic period-specific hormonal responses, these data advise that following an acute or repeated stressor an adolescent individual experiences greater exposure to the glucocorticoids than an adult.

Stress and the Adolescent Brain: a Perfect Storm?

As alluded to above, the encephalon is a major target of the glucocorticoids and these hormones are known to be potent modulators of many neurobiological processes, including neuronal plasticity (McEwen, 2007). In adults, chronic exposure to stress results in smaller and structurally less complex hippocampal and prefrontal cortical neurons. These morphological changes are also paralleled by decreases in spatial learning and attention shifting, cerebral abilities reliant upon an intact hippocampus and prefrontal cortex, respectively. Neurons in the amygdala, conversely, evidence stress-induced growth in adulthood, along with increased amygdala-dependent fear learning (McEwen, 2007). Importantly, these effects of stress on the adult brain are reversible, such that if animals are allowed to recover from the stressors for at least 10 days, and so these parameters revert to their pre-stress levels (McEwen, 2007).

Though we know relatively piffling about how stressors experienced during boyhood may influence the immediate and long-term structure and part of the encephalon, many factors may converge during this phase of development that may brand the adolescent encephalon specially vulnerable to stressors. Get-go, contempo longitudinal structural neuroimaging studies have indicated that the areas known to be the most sensitive to stress in adulthood, namely the hippocampus, prefrontal cortex, and amygdala, all keep to mature during boyhood (Giedd & Rapoport, 2010). 2nd, the adolescent brain may be more responsive to the glucocorticoids than the adult brain, as a previous animal study indicated that an equivalent dose of corticosterone increased cistron expression to a greater degree in the adolescent compared to adult hippocampus (Lee, Brandy, & Koenig, 2003). Finally, due to the increases in hormonal stress reactivity described above, information technology would appear that these maturing and exquisitely stress-sensitive brain regions in the adolescent would exist exposed to greater and more prolonged levels of glucocorticoids. Thus, like a "perfect storm", the convergence of these factors may render the adolescent encephalon especially vulnerable to perturbations, and hence psychological morbidities (Romeo & McEwen, 2006).

Unfortunately, there is a scarcity of studies that straight compare the effects of stress on the boyish and adult brain, and fewer that track whether these effects are more indelible if the stressors occur during adolescence. Thus, support for the notion that the boyhood brain may be particularly sensitive to stress has yet to be thoroughly tested empirically. A growing torso of inquiry, however, has begun to study on the effects of acute and chronic stress exposure on the structure and role of the adolescent brain. Studies in young adult rats indicated that previous exposure to chronic stress during adolescence resulted in reduced structural plasticity in the hippocampus and prefrontal cortex, and increased plasticity in the amygdala (Eiland, Ramroop, Colina, Manely, & McEwen, 2012; Isgor, Kabbaj, Akil, & Watson, 2004). Additional animal studies using models of social stress during boyhood (e.g., social instability, isolation) take also indicated decreases in markers of neural plasticity, such every bit neurogenesis and synaptic connectivity (Leussis & Andersen, 2008; McCormick, Nixon, Thomas, Lowie, & Dyck, 2010). These stress-induced alterations in the adolescent brain are also associated with compromised emotional function and cognitive skills (Eiland et al., 2012; Isgor et al., 2004; Leussis & Andersen, 2008). Although from these data information technology would seem that the bear upon of chronic stress on the adolescent and adult brain is similar, 1 important difference may be in the reversibility of these effects. Specifically, fifty-fifty a month subsequently recovery from chronic adolescent stress, some of these structural and functional changes persist (Isgor et al., 2004; Leussis & Andersen, 2008). It would therefore announced that the effects of stress on the adolescent encephalon may exist longer lasting when compared to the adult. Future experiments will need to directly assess this possibility, likewise as explore whether there are other unique effects of stress on the structure and office of the adolescent brain.

Conclusions

The data reviewed above conspicuously indicate that adolescence is time of dramatic changes in HPA role and stress responsiveness. Boyhood is also a pregnant period of connected neural maturation, specifically within stress-sensitive limbic and cortical regions. Thus it is possible that prolonged or repeated exposure to stress may result in a heightened sensitivity to these stressors, ultimately leading to maladaptive neurobehavioral evolution. Though the physiological and psychological implications of stress on the adolescent brain are far from clear, the increases in stress-related dysfunctions during boyhood, such every bit anxiety, depression, schizophrenia, and drug corruption highlight the importance of a better understanding of the interaction between changes in stress reactivity and adolescent brain development.

Acknowledgments

Funding

Preparation of this article was supported in part by grants from the National Institutes of Health (MH-090224) and the National Scientific discipline Foundation (IOS-1022148).

Recommended Reading

• Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience. 2009;10:434–45. A highly attainable review on the impact of stress on the prenatal, neonatal, boyish, adult, and aged brain. [PubMed] [Google Scholar]
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• Romeo, R. D. (2010b). (See References). This review provides greater item of HPA changes during pubertal and adolescent maturation.
• Spear LP. The adolescent encephalon and age-related behavioral manifestations. Neuroscience and Biobehavioral Reviews. 2000;24:417–463. An all-encompassing and attainable review on the adolescent maturation of encephalon and behavior. [PubMed] [Google Scholar]

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