Puberty is a universal experience in normal human development, marking the transition from childhood to adulthood. It is accompanied by physical growth, brain maturation and sexual maturation resulting in reproductive capability . The transition through puberty is also marked by an increased risk for the onset of health problems related to behaviour and emotional control . The Childhood to Adolescence Transition Study (CATS) is a new longitudinal study of pubertal development that aims to prospectively examine the hormonal, psychological and social processes that may influence the onset and course of health problems between childhood and adolescence. This paper presents the research protocol for the study.
It was not until the middle of the 20th century that studies began to objectively quantify puberty . During the 1960s, Tanner and colleagues created a five-level staging system for external signs of pubertal development, which remains the primary system in use today [4–6]. The Tanner stages range from Stage 1, no external signs of pubertal development, to Stage 5, which indicates complete physical maturation. While Tanner described separate breast and pubic hair stages in girls and genital, testicular and pubic hair stages in boys, these are extremely highly correlated and are appropriately considered together as a single stage .
The onset of puberty is generally understood to be marked by progression to Tanner Stage 2, which normally occurs between 8 and 13 years in girls and about 6 to 12 months later in boys . However, this view of puberty as a unitary process with a distinct onset marked by physical changes, such as hair growth, genital and skin changes or menarche, is overly simplistic. Puberty is in fact a combination of physiological processes that originate with neuroendocrinological changes several years prior to the onset of physical signs . There are at least three separate neuroendocrine axes involved in the pubertal cascade; adrenarche, the activation of adrenal androgen production; gonadarche, the activation of the gonads proper, and the further activation of the growth hormone-insulin-like-growth factor (IGF) axis that occurs at puberty.
The activation of puberty is not well understood and remains under-researched. It is unlikely that a single event causes the onset of puberty but that it begins with the initiation of a complex neuroendocrine network . The timing of puberty has genetic components, with nutrition, development in utero, socioeconomic factors and demographic factors in childhood also contributing [1, 11].
Gonadarche, the best understood of the pubertal processes, results in sexual maturation and reproductive capability, and is physically marked by menarche in girls and spermarche in boys. It is initiated by the transition from tonic to pulsatile secretion of gonadotrophin releasing hormone (GnRH), which in turn leads to increased pituitary secretion of the gonadotrophins, follicle-stimulating hormone (FSH) and luteinising hormone (LH) . Puberty as a whole is usually complete within 2–4 years following the onset of gonadarche, although time-dependent effects of sex steroids continue throughout life. However, prior to gonadarche, adrenal androgens, such as androstenedione, dehydroepiandrosterone (DHEA) and its sulphate DHEA-S begin rising, from around 6 to 8 years of age, with the maturation of the adrenal cortex in a process known as adrenarche .
Adrenarche is a feature of higher primate development not seen in other mammalian species apart from chimpanzees and gorillas . Adrenarche is described by some researchers as 'adrenal puberty’, with the underlying physiological processes less well understood than those associated with gonadarche . Adrenarche may play a role in the extension of the preadolescent phase on human ontogeny, promoting prolonged brain development of the pre-frontal cortex . Adrenal androgens have a role in the development of axillary and pubic hair, the emergence of acne, particularly in females, and may play an important role in brain maturation . Adrenal androgens are also precursors of the sex steroids testosterone and oestrogens . It is now also clear that adrenal androgens exert direct behavioural effects and influence brain function before full reproductive maturity .
Pubertal development and mental health and behaviour problems
Humans are the only animals to demonstrate major central nervous system (CNS) development at the same time as puberty. Pubertal stage, rather than chronological age, has been associated with a number of health and behaviour problems, which often persist into adulthood [17–19]. Recognising and understanding the distinction between pubertal stage (Tanner stage) and timing (onset relative to peers) is important. To illustrate, there is evidence that the timing of adrenarche and/or gonadarche might affect risk of physical and mental health problems [20, 21]. The speed of transition (i.e, the tempo through puberty) may itself be linked with health and behaviour problems, although this is an area that has received little research [3, 22]. The health problems associated with puberty and central to this study will be reviewed below and include:
Mental health problems
Antisocial behaviour and substance use
Physical health problems and functional somatic syndromes
Other problems such as impaired sleep and academic performance.
Mental health problems
There is evidence that there has been a rise in adolescent mental health problems in recent decades . Early puberty has been implicated in the emergence of mental health problems. Early maturing girls are more likely to have both internalising and externalising problems, while early maturing boys show higher rates of externalising symptoms . Depression is more common in adult females than males, although not before puberty. This gender dimorphism emerges during puberty as a function of pubertal stage rather than age, implicating the biological changes associated with puberty [17, 19, 25]. Similarly, pubertal stage rather than age has been shown to be the stronger predictor of panic attack occurrence and eating disorders [18, 26]. Both panic attacks and eating disorders are rare before puberty but increase dramatically in females during pubertal development [18, 26]. In the past, Attention-Deficit/Hyperactivity Disorder (ADHD) was considered a childhood disorder that disappeared as children reached adolescence. However, subsequent research has demonstrated that ADHD is a chronic disorder that can persist into adolescence and adulthood . To date, there have been no studies examining the role of puberty and age in ADHD onset . However, there is some evidence from clinical studies that DHEA and DHEA-S are inversely correlated with ADHD symptoms .
Antisocial behaviour and substance use
Puberty has been linked with antisocial behaviour in several studies. Males who enter puberty early have higher rates of antisocial behaviour during adolescence [29, 30]. Pubertal stage has also been shown to be an important risk factor for antisocial behaviour. Rates of violent behaviour and aggression were found to be significantly higher in mid- and late-puberty compared with early puberty . For substance use, similar patterns have also been identified. Females entering puberty early have been found to have an increased use of tobacco and alcohol in adolescence [32, 33].
Physical health problems and functional somatic syndromes
Estimates suggest that 10% of adolescents have a chronic physical health condition . Pubertal timing and stage are risk factors for a number of physical health and functional somatic syndromes. To illustrate, individuals with asthma who enter puberty early are at greater risk of their condition persisting into adolescence and having increased severity in adulthood . Pubertal development has also been found to be a better predictor than age of functional somatic syndromes in adolescents . Like depression, many functional somatic syndromes are more common in females than males and this difference in prevalence emerges during puberty . In line with this, female reproductive hormones are associated with an increased risk of migraine . However, research in this area has largely been cross-sectional and so longitudinal studies are needed to examine causal pathways.
Early puberty has been linked with a number of health problems occurring later in life, such as some cancers and cardiovascular disease. Early menarche increases the risk for breast cancer leading to the suggestion that increased exposure to oestradiol and/or progesterone over time may contribute to this increased risk . Similarly, girls with earlier menarche have also been shown to be at increased risk for mortality and cardiovascular disease, compared with girls maturing later, with some evidence that later puberty is protective .
Some research indicates that the timing of puberty can affect performance at school. However, these findings are limited and mixed, with some evidence suggesting children entering puberty earlier received lower grades  and other studies finding the opposite pattern . More research examining this relationship is needed, with detailed measures of puberty. Sleep disturbance in adolescents is common . Sleep problems range from insufficient sleep to more severe problems such as sleep apnoea. Sleep disturbance can have a significant impact on functioning and development, and can affect a range of factors such as academic performance and mood . Nevertheless, few studies have investigated the association between sleep and psychiatric disorders in adolescents, or the effect of puberty on changes in sleep patterns and sleep disturbance. Such associations are plausible, given that sleep requirements change markedly in early adolescence at the same time as puberty, and that melatonin, a pineal hormone, which is one of the key physiological regulators of the sleep cycle, changes with puberty in healthy humans .
Risk factors for early puberty
Early puberty may place an individual at risk for a variety of health and behaviour problems, and it is important to understand factors that may influence pubertal timing. A number of factors have been associated with early puberty, such as obesity, low socioeconomic status, psychosocial stress and absence of a biological father . However, many of these studies view puberty as a single, discrete process, and do not differentiate between adrenarche and gonadarche. For example, menarche, an event occurring late in gonadarche, has been found to begin five months earlier in obese-overweight children compared with normal weight peers . In contrast, high quality parental investment and lower marital conflict have been shown to predict later adrenarche . This is consistent with life history theory, an emerging framework attempting to explain the causes and effects of individual differences in pubertal timing [48–50]. Life history theory proposes that the environment experienced during infancy and childhood (and probably prenatally) influences children’s reproductive strategies and thus, affects the timing of the transition into adolescence, marked by adrenarche .
Limitations of existing research on pubertal development and health
To date, studies of pubertal development and health have been limited across various methodological areas including: a reliance on proxy measures of pubertal development; unclear and inconsistent use of definitions; cross-sectional designs; small sample sizes, and female only samples . In a review of studies measuring puberty, almost a quarter of studies did not provide enough information to determine if puberty was measured by physical examination or self-report, making interpretation and replication difficult . Age at menarche has been frequently used as an indicator of puberty in studies of pubertal development and mental health [19, 51, 52]. This marker is obviously limited to girls, occurs late in the pubertal process with almost two-thirds of girls reaching menarche in Tanner Stage 4 , and there is wide variability in self-reporting . The first studies measuring hormones in relation to normal pubertal development were conducted during the 1980s [21, 54, 55]. However, studies often included participants that were too old to allow adrenarche to be studied . Additionally, studies examining hormone concentrations have tended to use small sample sizes, with a few hundred participants at most, probably as a result of the cost and practicalities of collecting these samples [56–59].
Finally, the focus of previous work has been on puberty as a unitary physical process (e.g., Tanner staging) or the physical signs of gonadarche (e.g., menarche). Very little research has considered the role of adrenarche and its specific relationship with health and behaviour, or the interaction between adrenarche and gonadarche. As adrenarche and gonadarche represent different endocrine axes, it is critical to consider both processes when examining the role of puberty in health and behavioural development . This failure to distinguish between adrenarche and gonadarche may contribute to the sometimes confusing and contradictory findings, which have emerged in the field.
In summary, no previous study has examined adrenarche in a large cohort and adequately examined whether differences in pubertal, social, lifestyle and biological transitions may explain the emergence of health and behaviour problems. This is despite evidence for the role of adrenarche in brain development during this period, and that adolescent onset mental and behavioural disorders have become more common in recent decades .
Aims of CATS
The long-term aim of CATS is to prospectively examine how the timing and sequencing of hormonal events during puberty are associated with the onset and course of emotional, behavioural, social and learning problems through childhood and adolescence. In addition, the study will examine the influence and interaction of children’s psychological style and social context on the emergence of these problems during puberty. The first phase of this study begins in Grade 3, when children are 8–9 years of age, which will allow us to assess adrenarche. The broad research aim of this phase is to examine the associations between the onset of adrenarche and rates of emotional, behavioural and social problems. Our initial specific aims for the first phase of the study are:
To describe adrenal hormones and pubertal development in relation to adrenarche in 8–9 year old children.
To examine correlates, including both early life and current correlates, of the variation of the timing of adrenarche with a particular focus on anthropometry and social context.
To examine the associations between early adrenarche and emotional, behavioural, social and learning problems in 8–9 year old children.