Endocrine markers of puberty timing and antisocial behaviour in girls and boys.

BACKGROUND: Early puberty is associated with higher than average risk of antisocial behaviour, both in girls and boys. Most studies of such association, however, have focused on psychosocial mediating and moderating factors. Few refer to coterminous hormonal measures. AIM: The aim of this review is to consider the role of hormonal markers as potential mediating or moderating factors between puberty timing and antisocial behaviour. METHOD: A systematic literature search was conducted searching Medline, Embase, Web of Science, Scopus, Psycinfo, Cochrane and Google Scholar. RESULTS: Just eight studies were found to fit criteria, all cross-sectional. Measurements were too heterogeneous to allow meta-analysis. The most consistent associations found were between adrenal hormones-both androgens and cortisol-which were associated with early adrenarche and antisocial behaviours in girls and later adrenarche and antisocial behaviour in boys. CONCLUSIONS: The findings from our review suggest that longitudinal studies to test bidirectional hormone-behaviour associations with early or late puberty would be worthwhile. In view of the interactive processes between hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, integrated consideration of the hormonal end products is recommended.

Unfavorable Hormonal and Psychologic Profile in Adult Women with a History of Premature Adrenarche and Pubarche, Compared to Women with Polycystic Ovary Syndrome.

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm3). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised.

Relationships between adrenarcheal hormones, hippocampal volumes and depressive symptoms in children.

Early timing of puberty (i.e., advanced pubertal maturation relative to same-age peers) has been associated with depressive symptoms during adolescence. To date, research on this relationship has focused on gonadarche, the second phase of puberty, while less is known about the first phase of puberty, adrenarche. Increasing evidence suggests that androgens that rise during adrenarche, most notably dehyrdoepiandrosterone (DHEA) and testosterone, may be involved both in the development of the hippocampus, and risk for depression. The current study investigated whether hippocampal volumes mediated the relationship between adrenarcheal timing (based on relative levels of adrenarcheal hormones) and depressive symptoms in children. Data were collected from a cross-sectional sample of 88 children (46 female) selected to have relatively increased variance in these androgens. Participants completed brain MRI structural scans, provided saliva samples for hormones, and completed the Children's Depression Inventory (CDI). Contrary to predictions, larger right hippocampi significantly partially mediated the positive relationship between early timing of testosterone exposure (i.e., relatively high levels of testosterone for one's age) and depressive symptoms in girls. No other evidence of significant mediation effects was obtained, however DHEA and testosterone exposure showed unique effects on hippocampal volumes in males and females, and larger hippocampal volumes predicted higher depressive symptoms in the entire sample. These results suggest that adrenarcheal timing may be related to hippocampal development and depressive symptoms, extending current knowledge of pubertal risk processes.

Increased symptoms of anxiety and depression in prepubertal girls, but not boys, with premature adrenarche: associations with serum DHEAS and daily salivary cortisol concentrations.

Concerns over anxiety and depressive symptoms in children with premature adrenarche (PA) have been recently raised. However, to date, most relevant studies are on a small number of girls. In this cross-sectional study, 82 pre-pubertal children (66 girls and 16 boys) diagnosed with PA, were compared to 63 control children regarding their psychological characteristics and hypothalamic-pituitary-adrenal (HPA) axis function, as assessed by salivary cortisol measurement. Symptoms of anxiety and depression were assessed by child self-report (Spence Children's Anxiety Scale (SCAS) and Depression self-rating scale for Children (DSRS)) and parent-report (Child Behaviour Checklist (CBCL)) tests validated for the Greek population. Salivary cortisol levels were determined directly after awakening (approximately 7am) and evening (8pm) of the same day. Morning serum DHEAS levels were assessed in PA children. Girls with PA scored significantly higher on anxiety (p = .016) and depression (p =.039) scales than controls. No group differences were noted for parent reports and children's salivary cortisol concentrations. Boys with PA did not demonstrate significant differences in any of the aforementioned parameters. Our findings suggest that girls with PA may be at higher risk for reporting symptoms of anxiety and depression than their non-PA peers. HPA axis dysregulation in this population was not documented.

Children with a History of Premature Adrenarche Have Good Health-Related Quality of Life at the Age of 12 Years.

BACKGROUND/AIM: Children with premature adrenarche (PA) are taller and more overweight than their healthy peers, and PA girls have a slightly accelerated pubertal development. There is some evidence that early exposure to androgens may have an influence on psychosocial development. The aim of this cross-sectional case-control study was to evaluate health-related quality of life (HRQoL) in PA children at the age of 12 years. METHODS: The HRQoL was assessed for 43 PA (36 girls) and 63 control children (52 girls) at the median age of 12.0 years using the standardized 16D instrument, and the scores of the PA children were compared to those of the control children and reference population. RESULTS: The mean overall HRQoL scores did not differ between PA and control girls, PA and control boys, or all PA and control children or the reference population. Independently of PA, overweight girls had a lower mean overall HRQoL score than lean girls, and both overweight girls and boys were on average worse off on the dimension of appearance than their lean peers. CONCLUSIONS: PA children have as good self-rated HRQoL as their peers at the age of 12 years. Overweight is associated with a worse HRQoL profile independently of PA.

One-Year Follow-Up of Girls with Precocious Puberty and Their Mothers: Do Psychological Assessments Change over Time or with Treatment?

BACKGROUND: To determine whether psychological characteristics of girls with variations of early puberty and their mothers change over time and with treatment in girls with central precocious puberty (CPP). METHODS: Girls with CPP, premature adrenarche (PA), and early normal puberty (ENP) completed psychological assessments at baseline and after 1 year along with their mothers. All girls with CPP were treated with GnRH analogs. Psychological effects of group and time were examined using 2 × 3 mixed ANOVAs. RESULTS: Sixty-two subjects aged 7.5 ± 1.4 years (range 4.8-10.5) were enrolled, of whom 36 (15 with CPP, 8 with PA, and 13 with ENP) completed 1-year follow-up assessments. Psychological measures were normal in all girls. No significant group differences were found for any measure of girls' psychological functioning at either time point. However, across all groups there was change over time with a decrease in perceived physical competence (p < 0.001) and an increase in perceived maternal acceptance (p = 0.001). CONCLUSION: No abnormalities in psychological functioning were found among girls with variations of early puberty, and all groups were in the normal range. Our results are largely reassuring regarding concerns of adverse psychological consequences of early puberty in girls.

Associations between dehydroepiandrosterone (DHEA) levels, pituitary volume, and social anxiety in children.

Early timing of adrenarche, associated with relatively high levels of dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) in children, has been linked with mental health problems, particularly anxiety. However, little is known about possible neurobiological mechanisms underlying this association. The pituitary gland is a key component of the hypothalamic-pituitary-adrenal (HPA) axis, the activation of which triggers the onset of adrenarche. The purpose of this study was to examine the extent to which pituitary gland volume mediated the relationship between levels of DHEA/DHEA-S relative to age (i.e., adrenarcheal timing) and symptoms of anxiety in 95 children (50 female, M age 9.50 years, SD 0.34 years). Relatively high DHEA and DHEA-S (DHEA/S) levels were found to be associated with larger pituitary gland volumes. There was no significant direct effect of relative DHEA/S levels on overall symptoms of anxiety. However, results supported an indirect link between relatively high DHEA/S levels and symptoms of social anxiety, mediated by pituitary gland volume. No sex differences were observed for any relationship. Our findings suggest that neurobiological mechanisms may be partly responsible for the link between relatively early adrenarche and anxiety symptoms in children. One possible mechanism for this finding is that an enlarged pituitary gland in children experiencing relatively advanced adrenarche might be associated with hyper-activity/reactivity of the HPA axis. Further research is needed to understand the role of stress in the link between adrenarcheal timing and HPA-axis function, especially in relation to the development of anxiety symptoms in children and adolescents.

Depression, immune function, and early adrenarche in children.

Despite consistent findings of an association between depression and immunity in adult and adolescent populations, little is known about the nature of this relationship at earlier ages. Studies of children have yielded mixed results, suggesting methodological confounds and/or the presence of significant moderating factors. Timing of adrenarche, the first phase of puberty that occurs during late childhood, is a plausible moderator of the depression-immunity relationship in late childhood due to its associations with both the immune system and psychological wellbeing. We hypothesized that: (1) a depression-immunity association exists in children, (2) this association is moderated by adrenarcheal timing, and, (3) this association is also moderated by gender. Data were drawn from a nested study of 103 participants (62 females, Mage=9.5, age range: 8.67-10.21 years) participating in a population based cohort study of the transition from childhood to adolescence (across puberty). Participants in this nested study completed the Children's Depression Inventory 2 (CDI-2) and provided morning saliva samples to measure immune markers (i.e., C-reactive protein, CRP; and secretory immunoglobulin A, SIgA). Using hierarchical regression, inflammation measured by CRP was positively associated with the negative mood/physical symptoms (NM/PS) subscale (ß=0.23, t=2.33, p=0.022) of the CDI-2. A significant interaction effect of SIgA x adrenarcheal timing was found for NM/PS (ß=-0.39, t=-2.19, p=0.031) and Interpersonal Problems (ß=-0.47, t=-2.71, p=0.008). SIgA and NM/PS were positively associated for relatively late developers. SIgA and Interpersonal Problems were positively associated for late developers, and negatively associated for early developers. We suggest that both sets of findings might be partially explained by the immunosuppressive effect of the hormonal changes associated with earlier adrenarche, namely testosterone. These results also suggest that adrenarcheal timing has an effect on the association between depression and immunity, and is therefore an important measure in research with younger populations. Future research should utilize longitudinal designs to demonstrate direction of influence of variables, and use a broader range of pro- and anti-inflammatory markers.

Adrenarche and the Emotional and Behavioral Problems of Late Childhood.

PURPOSE: Mental and behavioral disorders increase in prevalence with the passage through puberty. Yet the first symptoms for many children emerge between seven and 11 years, before the pubertal rise in gonadal hormones. A possibility that symptom onset may be linked to the adrenarchal rise in androgens has been little explored. METHODS: The Childhood to Adolescence Transition Study recruited a stratified random sample of 1,239 eight-nine year olds from primary schools in Melbourne, Australia. Saliva samples were assayed for dehydroepiandrosterone, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. Emotional and behavioral problems were assessed through parental report on the Strengths and Difficulties Questionnaire. RESULTS: In males, high levels of all androgens were associated with greater total difficulties and peer problems. Higher dehydroepiandrosterone and testosterone were associated with emotional symptoms and DHEA-S with conduct problems. In females, DHEA-S was associated with peer problems. CONCLUSIONS: In late childhood, androgens are associated with emotional and behavioral problems in males, raising a possibility that the adrenarchal transition plays a contributing role. If so, the late primary school years may prove to be an important phase for preventing the onset of mental health and behavioral problems in boys.

Study protocol: the Childhood to Adolescence Transition Study (CATS).

BACKGROUND: Puberty is a multifaceted developmental process that begins in late-childhood with a cascade of endocrine changes that ultimately lead to sexual maturation and reproductive capability. The transition through puberty is marked by an increased risk for the onset of a range of health problems, particularly those related to the control of behaviour and emotion. Early onset puberty is associated with a greater risk of cancers of the reproductive tract and cardiovascular disease. Previous studies have had methodological limitations and have tended to view puberty as a unitary process, with little distinction between adrenarche, gonadarche and linear growth. The Childhood to Adolescence Transition Study (CATS) aims to prospectively examine associations between the timing and stage of the different hormonally-mediated changes, as well as the onset and course of common health and behavioural problems that emerge in the transition from childhood to adolescence. The initial focus of CATS is on adrenarche, the first hormonal process in the pubertal cascade, which begins for most children at around 8 years of age. METHODS/DESIGN: CATS is a longitudinal population-based cohort study. All Grade 3 students (8-9 years of age) from a stratified cluster sample of schools in Melbourne, Australia were invited to take part. In total, 1239 students and a parent/guardian were recruited to participate in the study. Measures are repeated annually and comprise student, parent and teacher questionnaires, and student anthropometric measurements. A saliva sample was collected from students at baseline and will be repeated at later waves, with the primary purpose of measuring hormonal indices of adrenarche and gonadarche. DISCUSSION: CATS is uniquely placed to capture biological and phenotypic indices of the pubertal process from its earliest manifestations, together with anthropometric measures and assessment of child health and development. The cohort will provide rich detail of the development, lifestyle, external circumstances and health of children during the transition from childhood through to adolescence. Baseline associations between the hormonal measures and measures of mental health and behaviour will initially be examined cross-sectionally, and then in later waves longitudinally. CATS will make a unique contribution to the understanding of adrenarche and puberty in children's health and development.

Executive functioning, cortisol reactivity, and symptoms of psychopathology in girls with premature adrenarche.

The study examined the interaction between early maturational timing (measured by premature adrenarche [PA]) and executive functioning and cortisol reactivity on symptoms of psychopathology. The study included 76 girls aged 6 through 8 years (mean = 7.50, SD = 0.85) with PA (n = 40) and on-time adrenarche (n = 36). Girls completed a battery of psychological and neuropsychological tests and blood sampling for cortisol. Parents completed the Child Behavior Checklist. The results demonstrated that girls with PA with lower levels of executive functioning had higher externalizing and anxious symptoms compared to other girls. In addition, girls with PA who demonstrated increases in serum cortisol had higher externalizing symptoms than those with stable patterns. Finally, girls with PA who demonstrated decreases in cortisol reported higher depressive symptoms. The findings from this study provide important information concerning the impact of cognitive functioning and stress reactivity on adjustment to early maturation in girls with PA. The results of this research may inform screening and intervention efforts for girls who may be at greatest risk for emotional and behavioral problems as a result of early maturation.

Adrenarche and middle childhood.

Middle childhood, the period from 6 to 12 years of age, is defined socially by increasing autonomy and emotional regulation, somatically by the development of anatomical structures for subsistence, and endocrinologically by adrenarche, the adrenal production of dehydroepiandrosterone (DHEA). Here I suggest that DHEA plays a key role in the coordinated development of the brain and body beginning with middle childhood, via energetic allocation. I argue that with adrenarche, increasing levels of circulating DHEA act to down-regulate the release of glucose into circulation and hence limit the supply of glucose which is needed by the brain for synaptogenesis. Furthermore, I suggest the antioxidant properties of DHEA may be important in maintaining synaptic plasticity throughout middle childhood within slow-developing areas of the cortex, including the insula, thamalus, and anterior cingulate cortex. In addition, DHEA may play a role in the development of body odor as a reliable social signal of behavioral changes associated with middle childhood.

Sex, attachment, and the development of reproductive strategies.

This target article presents an integrated evolutionary model of the development of attachment and human reproductive strategies. It is argued that sex differences in attachment emerge in middle childhood, have adaptive significance in both children and adults, and are part of sex-specific life history strategies. Early psychosocial stress and insecure attachment act as cues of environmental risk, and tend to switch development towards reproductive strategies favoring current reproduction and higher mating effort. However, due to sex differences in life history trade-offs between mating and parenting, insecure males tend to adopt avoidant strategies, whereas insecure females tend to adopt anxious/ambivalent strategies, which maximize investment from kin and mates. Females are expected to shift to avoidant patterns when environmental risk is more severe. Avoidant and ambivalent attachment patterns also have different adaptive values for boys and girls, in the context of same-sex competition in the peer group: in particular, the competitive and aggressive traits related to avoidant attachment can be favored as a status-seeking strategy for males. Finally, adrenarche is proposed as the endocrine mechanism underlying the reorganization of attachment in middle childhood, and the implications for the relationship between attachment and sexual development are explored. Sex differences in the development of attachment can be fruitfully integrated within the broader framework of adaptive plasticity in life history strategies, thus contributing to a coherent evolutionary theory of human development.

Differences in endocrine parameters and psychopathology in girls with premature adrenarche versus on-time adrenarche.

Girls with premature adrenarche (PA) are at risk for multiple problems related to exaggerated androgen synthesis. Whether PA carries a risk of psychopathology remains unknown. This study examined group differences in: (a) anthropometric and endocrine parameters, and (b) mood and behavior problems, in 6-8 year-old girls with PA (n = 40) compared to on-time adrenarche girls (n = 36). PA girls were taller (p < or =0.05) and heavier (p < or =0.01) than the on-time adrenarche girls but body mass index showed no difference. PA girls had significantly (p <0.05) higher adrenal androgen and testosterone concentrations but not cortisol or leptin. PA girls also had significantly more oppositional defiant disorder, and higher symptom counts reflecting anxiety, mood or disruptive behavior disorders. PA girls may be more vulnerable to psychopathology than on-time adrenarche girls. The challenge of future studies is to determine which PA girls are at risk for psychopathology and which are more resilient.

Juvenility in the context of life history theory.

Homo sapiens is unique in having four prolonged and pronounced postnatal pre-adult life history stages: infancy, which lasts for 30-36 months and ends with weaning from breast feeding in traditional societies; childhood, which lasts for an additional 2-4 years and concludes in a degree of independence as regards protection and food provision; a juvenile stage of 3-4 years that terminates with readiness for sexual maturation; and adolescence, which lasts for 3-5 years and culminates in fertility. Juvenility implies two transitional periods which are only experienced by humans: a transition from childhood to juvenility and from juvenility to adolescence. Juvenility, "the age of reason and responsibility" and concrete operation, coincides with elementary school age and offers opportunities to prepare for the social complexity of adolescence. Here I define the transition to juvenility by three variables: adrenarche (the onset of adrenal androgen generation), growth pattern (decelerating from a linear childhood growth velocity) and adiposity rebound acceleration of body mass index. The data presented suggest that this period is endowed with programming/predictive adaptive responses of body composition to the environment.

Family environments, adrenarche, and sexual maturation: a longitudinal test of a life history model.

Life history theorists have proposed that humans have evolved to be sensitive to specific features of early childhood environments and that exposure to different environments biases children toward development of different reproductive strategies, including differential pubertal timing. The current research provides a longitudinal test of this theory. Assessments of family environments, based on interviews with mothers and fathers, were conducted in preschool, and children were then followed prospectively through middle childhood. Adrenal hormones were assayed in a selected subsample of 120 children (73 girls) at age 7, and parent and child reports of secondary sexual characteristics were collected in the full female sample of 180 girls at age 11. Higher quality parental investment (from both mothers and fathers) and less father-reported Marital Conflict/Depression forecast later adrenarche. Older age at menarche in mothers, higher socioeconomic status, greater mother-based Parental Supportiveness, and lower third-grade body mass index each uniquely and significantly predicted later sexual development in daughters. Consistent with a life history perspective, quality of parental investment emerged as a central feature of the proximal family environment in relation to pubertal timing.