Attenuated hypothalamic-pituitary-adrenal axis functioning predicts accelerated pubertal development in girls 1 year later.

Pubertal development signals an important juncture in the transition from childhood to adulthood. The timing and tempo of puberty are variable, and individual differences have been linked with health outcomes (Marceau, Ram, Houts, Grimm, & Susman, 2011). For example, early puberty has been associated with heightened risk of psychological symptoms (Graber, Lewinsohn, Seeley, & Brooks-Gunn, 1997; Negriff & Susman, 2011) as well as physical health problems like obesity (Wang, 2002) and breast cancer (Bernstein, 2002; Sellers et al., 1992). Although genetic effects have been found to account for 50%–80% of the variability in pubertal timing across studies (Palmert & Hirschhorn, 2003), environmental factors, including psychosocial stressors, have also been associated with pubertal development (Belsky, Steinberg, & Draper, 1991; Graber, Brooks-Gunn, & Warren, 1995). The question of how stress influences pubertal development is complex, given evidence that stress both delays pubertal development in some cases (as has been found during extreme privation, e.g., famine and war) and accelerates it in others (e.g., in the context of father absence or family adversity; Ellis, 2004). At the hormonal level, the hypothalamic–pituitary–adrenal (HPA) axis, which secretes glucocorticoids, the main one cortisol, is known to have a suppressive effect on the hypothalamic–pituitary–gonadal (HPG) axis (Chrousos & Gold, 1992). The HPG axis is responsible for reproduction, communicates with the gonads, and coordinates the release of sex hormones as well as multiple other metabolic processes. When threat is imminent, the body diverts resources toward the threat and away from longer range goals such as reproduction, growth, and immunity. When a stressful experience or anticipation activates the HPA axis, reproductive system activity is correspondingly dampened via the suppressive effects of HPA axis hormones on the luteinizing hormone-releasing hormone. HPA axis activation also inhibits pituitary gonadatrophs and the gonad itself, and renders target tissues for sex steroids (i.e., testes and ovaries) more resistant to these hormones (Chrousos & Gold, 1992). This inhibiting effect of physiological or emotional stress on the reproductive system, in the context of puberty, has been labeled “stress-suppression theory” (Ellis, 2004) and has been supported by evidence that puberty appears delayed among subordinate primates (French, 1997) and among youth exposed to extreme stress and trauma, such as during war (Prebeg & Bralic, 2000). However, a more recent study found changes in the coupling of the HPA and HPG axes over adolescence that appeared modulated by early life stress (Ruttle, Shirtcliff, Armstrong, Klein, & Essex, 2013). Specifically, HPA–HPG “cross-talk” appeared weakly positive at age 11 but shifted to more adult like negative coupling by age 15. Girls exposed to early stress showed an earlier shift to the latter pattern, with negative HPA–HPG coupling appearing by age 13. In contrast to stress-suppression theory, other theories of environmental effects on puberty (e.g., psychosocial acceleration theory, paternal investment theory, and child development theory; reviewed by Ellis, 2004) posit an opposite direction of effects, with more stressful rearing environments predicting accelerated pubertal development. These theories have received empirical support, with factors like father absence, harsh or unsupportive parenting, parental unemployment, and family conflict associated with earlier pubertal development in girls (e.g., Arim et al., 2011; Belsky et al., 2007; Deardorff et al., 2011; Ellis & Garber, 2000), while positive family characteristics like approval and warmth have been linked with delayed pubertal development (Graber et al., 1995). These findings of psychosocial effects on puberty appear to be robust across a variety of assessment approaches, including physician assessment of Tanner stages (as used in papers such as Belsky et al., 2007, and Deardorff et al., 2011), and self-reported or parent-reported pubertal development using measures such as the Pubertal Development Scale (PDS; Petersen, Crockett, Richards, & Boxer, 1988; used in Arim et al., 2011; Ellis & Garber, 2000). A number of possible mechanisms have been proposed to explain these findings, such as genes, pheromones (related to the presence of familial or extrafamilial males), body fat (with stress-related weight gain triggering earlier puberty), and stress hormones. Despite the fact that stress hormones have been mentioned as a possible mechanism, few studies have actually measured stress hormones or used prospective designs, so the contributions of HPA axis functioning to psychosocial effects on puberty remain unstudied. In speculating about the HPA axis as a mechanism linking stress with accelerated pubertal development, researchers (e.g., Ellis & Garber, 2000; Ellis, 2004) have pointed to the interaction of the HPA and HPG axes, but they have noted that findings to date (linking higher family stress to earlier onset and faster tempo of puberty) present a paradox given that the HPA axis is known to suppress the HPG axis. The “attenuation hypothesis” (Susman, 2006) helps to reconcile this apparently “paradoxical” relationship between psychosocial stress and accelerated puberty. According to this hypothesis, early, chronic stressful experiences may act to downregulate the stress system of some children, an adaptive strategy that protects the organism from the costs of continued adrenocortical overload. In support of this hypothesis, studies have linked early adversity with low baseline cortisol and attenuated reactivity to stress (e.g., Carpenter et al., 2007; Elzinga et al., 2008; Granger et al., 1998; Luecken, Kraft, & Hagan, 2009; Roisman et al., 2009). Previous investigations of the sample studied in this paper reported a history of maltreatment to be linked with low or attenuated patterns of cortisol responses to a stress task (Trickett, Gordis, Peckins, & Susman, in press). Youth whose maltreatment included physical or sexual abuse showed more pronounced attenuation, relative to youth who had experienced only neglect or emotional abuse, indicating that more severe maltreatment has a more suppressive effect on the HPA axis. Evidence that early life stress may dampen, rather than heighten, HPA axis functioning in some contexts suggests the intriguing and untested possibility that youths with attenuated HPA axis functioning might be at risk for earlier puberty through the reduction of HPA axis-mediated suppression of the HPG axis, or the removal of a “hormonal brake” regulating puberty. Besides the current study, the only study, to our knowledge, to explore HPA axis functioning as predictive of pubertal tempo (Ellis, Shirtcliff, Boyce, Deardorff, & Essex, 2011) reported results consistent with the above possibility. The authors sampled cortisol when children (59% girls) were in first grade and took self-report and mother-report PDS measures of pubertal development (averaged together) up to four times when children were between third and ninth grades. Children whose cortisol levels increased over a 4-hr laboratory protocol showed a trend (significant in the case of pubic hair development) toward slower initial tempo of pubertal development (up to age 12.5) followed by faster subsequent pubertal tempo (after age 12.5). The association between higher cortisol and slower initial pubic hair development was stronger among children who received supportive parenting, a finding the authors interpret in terms of the “biological sensitivity to context” hypothesis (e.g., youth who are more physiologically sensitive to their environments have especially positive outcomes in high-resource environments and especially negative outcomes in aversive environments; Boyce & Ellis, 2005). However, the study was not designed primarily to examine cortisol and is limited by the lack of a standardized stress protocol, such as the Trier Social Stress Test, designed to elicit a cortisol response; instead, the authors used the slope of cortisol (increasing or decreasing) over the course of the entire laboratory visit to index “adrenocortical reactivity.” The current report examines how HPA axis functioning in early to mid-puberty (ages 9–12) affects the tempo of pubertal development across approximately 1 year in a large, ethnically diverse sample of maltreated and nonmaltreated boys and girls. Because of its prospective design, this report can make a unique contribution to understanding the mechanisms of pubertal development. We hypothesize that HPA axis functioning at the first assessment (Time 1 [T1]) will be linked with tempo, modeled as pubertal stage at a second assessment (Time 2 [T2]), controlling for T1 pubertal stage. Given evidence that HPA activity suppresses HPG activity, we expect that attenuated cortisol, which has previously been associated with maltreatment in this sample (Trickett et al., in press), will predict accelerated puberty. In addition to looking at an overall measure of pubertal development, we will examine components of puberty that are assumed to reflect adrenal development (e.g., pubic hair development) and gonadal (breast/genital) development separately given that these are mediated by different hormones. Hypotheses will be tested separately for girls and for boys because the majority of past studies have focused exclusively on girls (Ellis, 2004), and then with boys and girls together to test the moderating role for gender. We also examined a possible moderating role for maltreatment, investigating whether an association between cortisol and puberty is stronger or weaker among youth with a history of maltreatment.