Melbourne School of Psychological Sciences - Research Publications
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ItemNo Preview AvailableEstradiol variability is associated with brain structure in early adolescent females(PERGAMON-ELSEVIER SCIENCE LTD, 2022-12)One-third of adolescents are diagnosed with a psychiatric disorder by age 16, with female adolescents twice as likely to experience an internalizing (i.e., depression or anxiety) disorder as their male peers. Individual differences in pubertal factors may partially underlie this disparity, potentially via the role of pubertal hormones in shaping brain development. While research has examined links between estradiol levels and brain structure, individual variation in estradiol levels has not been considered. Using longitudinal data from 44 female adolescents (baseline age M = 11.7; follow-up age M= 13.3), we examined associations between both average estradiol and estradiol variability, and brain gray matter structure at baseline. We used a hypothesis-driven region of interest (ROI) approach focusing on subcortical and ventromedial prefrontal regions, in addition to an exploratory whole-brain analysis. We also investigated whether brain structure mediated the association between estradiol measures and internalizing (i.e., anxious and depressive) symptoms at follow-up. ROI analyses revealed a significant negative association between estradiol variability and thickness of the right medial orbitofrontal cortex (OFC, β = -0.39, FDR corrected p = .010). There were, however, no significant associations between average estradiol or estradiol variability and internalizing symptoms, nor was there evidence of mediation. Our results indicate that increased variation in estradiol levels across a month is associated with decreased cortical thickness in a brain region implicated in emotion processing, although implications for mental health are unclear. Findings, however, highlight the importance of considering individual variation in estradiol when examining links to brain development.
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ItemNo Preview AvailableA longitudinal analysis of puberty-related cortical development(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2021-03)The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether individual differences in the rate of pubertal maturation (or "pubertal tempo") was associated with variations in cortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important individual differences in the coupling of these developmental processes.
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ItemThe effects of puberty and its hormones on subcortical brain development(ELSEVIER, 2021-08)Puberty triggers a period of structural "re-organization" in the brain, when rising hormone levels act via receptors to influence morphology. However, our understanding of these neuroendocrine processes in humans remains poor. As such, the current longitudinal study characterized development of the human subcortex during puberty, including changes in relation to pubertal (Tanner) stage and hormone (testosterone, dehydroepiandrosterone [DHEA]) levels. Beyond normative group-level patterns of development, we also examined whether individual differences in the rate of pubertal maturation (i.e., "pubertal/hormonal tempo") were associated with variations in subcortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age. Parents completed questionnaire assessments of pubertal stage at each wave, and adolescents provided hormone samples on a subset of waves. Generalized additive mixture models were used to characterize trajectories of subcortical development. Results showed that development of most subcortical structures was related to pubertal stage, although findings were mostly non-significant when controlling for age. Testosterone and DHEA levels were related to development of the amygdala, hippocampus and pallidum in both sexes, and findings in the amygdala remained significant when controlling for age. Additionally, we found that variability in hormonal (specifically testosterone) tempo was related to right hippocampal development in males, with an accelerated pattern of hippocampal development in those with greater increases in testosterone levels. Overall, our findings suggest prominent hormonal influences on the amygdala and hippocampus, consistent with the prevalence of androgen and estrogen receptors in these regions. We speculate that these findings are most likely reflective of the important role of adrenarcheal processes on adolescent brain development.
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ItemStudy protocol: the Childhood to Adolescence Transition Study (CATS)(BMC, 2013-10-08)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.
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ItemAssociations between adrenarcheal hormones, amygdala functional connectivity and anxiety symptoms in children(PERGAMON-ELSEVIER SCIENCE LTD, 2018-11)OBJECTIVE: The transition from childhood to adolescence is a vulnerable period for the development of anxiety symptoms. There is some evidence that hormonal changes occurring during adrenarche, an early pubertal phase, might play a role in this increased vulnerability. Little is known about underlying brain mechanisms. Given the role of the amygdala-based fear circuit in anxiety, the current study aimed to investigate whether children's adrenarcheal hormone levels were associated with functional connectivity of the amygdala while processing fearful facial expressions, and how this in turn related to anxiety symptoms. METHOD: Participants were 83 children (M age 9.53 years) who completed two morning saliva collections to measure levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS), and testosterone. They also completed the Spence Children's Anxiety Scale (SCAS), and viewed fearful and calm facial expressions while undergoing a functional MRI scan. Psychophysiological interaction (PPI) analyses were performed to examine amygdala connectivity and significant clusters were fed into a bootstrapping mediation model. RESULTS: In boys, mediation analyses showed an indirect positive effect of testosterone on anxiety symptoms, which was mediated by amygdala-secondary visual cortex connectivity as well as amygdala-anterior cingulate connectivity. In girls, DHEAS showed a negative indirect association with anxiety symptoms mediated by amygdala connectivity to the fusiform face area and insula. CONCLUSION: The results indicate unique roles for adrenarcheal hormones in anxiety and suggest that amygdala connectivity may represent an important neural mechanism in these associations. Importantly, results reveal prominent sex differences in the biological mechanisms associated with anxiety in children undergoing adrenarche.
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ItemBrain structural connectivity during adrenarche: Associations between hormone levels and white matter microstructure(PERGAMON-ELSEVIER SCIENCE LTD, 2018-02)Levels of the adrenal hormones dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and testosterone, have all been linked to behavior and mental health during adrenarche, and preclinical studies suggest that these hormones influence brain development. However, little is known about how variation in these hormones is associated with white matter structure during this period of life. The current study aimed to examine associations between DHEA, DHEAS, and testosterone, and white matter microstructure during adrenarche. To avoid the confounding effect of age on hormone levels, we tested these associations in 87 children within a narrow age range (mean age 9.56 years, SD=0.34) but varying in hormone levels. All children provided saliva samples directly after waking and completed a diffusion-weighted MRI scan. Higher levels of DHEA were associated with higher mean diffusivity (MD) in a widespread cluster of white matter tracts, which was partially explained by higher radial diffusivity (RD) and partially by higher axial diffusivity (AD). In addition, there was an interaction between DHEA and testosterone, with higher levels of testosterone being associated with higher fractional anisotropy (FA) and lower MD and RD when DHEA levels were relatively high, but with lower FA and higher MD and RD when DHEA levels were low. These findings suggest that relatively early exposure to DHEA, as well as an imbalance between the adrenal hormones, may be associated with alterations in white matter microstructure. These findings highlight the potential relevance of adrenarcheal hormones for structural brain development.
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ItemNo Preview AvailableAssociations between early adrenarche, affective brain function and mental health in children(OXFORD UNIV PRESS, 2015-09)Early timing of adrenarche, associated with relatively high levels of Dehydroepiandrosterone (DHEA) in children, has been associated with mental health and behavioral problems. However, little is known about effects of adreneracheal timing on brain function. The aim of this study was to investigate the effects of early adrenarche (defined by high DHEA levels independent of age) on affective brain function and symptoms of psychopathology in late childhood (N = 83, 43 females, M age 9.53 years, s.d. 0.34 years). Results showed that higher DHEA levels were associated with decreased affect-related brain activity (i) in the mid-cingulate cortex in the whole sample, and (ii) in a number of cortical and subcortical regions in female but not male children. Higher DHEA levels were also associated with increased externalizing symptoms in females, an association that was partly mediated by posterior insula activation to happy facial expressions. These results suggest that timing of adrenarche is an important moderator of affect-related brain function, and that this may be one mechanism linking early adrenarche to psychopathology.
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ItemSelf-Reported Parenting Style Is Associated With Children's Inflammation and Immune Activation(AMER PSYCHOLOGICAL ASSOC, 2017-04)Family environments and parenting have been associated with inflammation and immune activation in children and adolescents; however, it remains unclear which specific aspects of parenting drive this association. In this study, we cross-sectionally examined the association between 5 discrete parenting styles and inflammation and immune activation in late childhood. Data were drawn from 102 families (55 with female children, mean age 9.50 years, SD = 0.34) participating in the Imaging Brain Development in the Childhood to Adolescence Transition Study. Children provided saliva samples from which inflammation (C-reactive protein) and immune competence/activation (secretory immunoglobulin A) were measured. Parents completed the Alabama Parenting Questionnaire, which measures 5 aspects of parenting style-positive parental involvement, positive disciplinary techniques, consistency in disciplinary techniques, corporal punishment, and monitoring and supervision. Results showed that higher scores on the poor parental monitoring scale were associated with higher levels of both inflammation and immune activation in children. This study highlights parental monitoring and supervision as a specific aspect of parenting behavior that may be important for children's physical and mental health. (PsycINFO Database Record
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ItemStudy protocol: Imaging brain development in the Childhood to Adolescence Transition Study (iCATS)(BMC, 2014-04-30)BACKGROUND: Puberty is a critical developmental phase in physical, reproductive and socio-emotional maturation that is associated with the period of peak onset for psychopathology. Puberty also drives significant changes in brain development and function. Research to date has focused on gonadarche, driven by the hypothalamic-pituitary-gonadal axis, and yet increasing evidence suggests that the earlier pubertal stage of adrenarche, driven by the hypothalamic-pituitary-adrenal axis, may play a critical role in both brain development and increased risk for disorder. We have established a unique cohort of children who differ in their exposure to adrenarcheal hormones. This presents a unique opportunity to examine the influence of adrenarcheal timing on brain structural and functional development, and subsequent health outcomes. The primary objective of the study is to explore the hypothesis that patterns of structural and functional brain development will mediate the relationship between adrenarcheal timing and indices of affect, self-regulation, and mental health symptoms collected across time (and therefore years of development). METHODS/DESIGN: Children were recruited based upon earlier or later timing of adrenarche, from a larger cohort, with 128 children (68 female; M age 9.51 years) and one of their parents taking part. Children completed brain MRI structural and functional sequences, provided saliva samples for adrenarcheal hormones and immune biomarkers, hair for long-term cortisol levels, and completed questionnaires, anthropometric measures and an IQ test. Parents completed questionnaires reporting on child behaviour, development, health, traumatic events, and parental report of family environment and parenting style. DISCUSSION: This study, by examining the neurobiological and behavioural consequences of relatively early and late exposure to adrenarche, has the potential to significantly impact our understanding of pubertal risk processes.
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ItemThe lifetime experience of traumatic events is associated with hair cortisol concentrations in community-based children(PERGAMON-ELSEVIER SCIENCE LTD, 2016-01)Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal axis (HPAA) and increase risk for negative health outcomes. Recent research suggests that cortisol in scalp hair represents a promising measure of HPAA function. However, little is known about the relationship between early exposure to traumatic events and hair cortisol concentrations (HCC) in childhood, a critical period of HPAA development. The current study measured HCC in scalp hair samples collected from 70 community-based children (14 males, mean age=9.50) participating in the Imaging Brain Development in the Childhood to Adolescence Transition Study (iCATS). Data were also collected on lifetime exposure to traumatic events and current depressive symptoms. Lifetime exposure to trauma was associated with elevated HCC; however, HCC was not associated with current depressive symptoms. Consistent with some prior work, males were found to have higher HCC than females, although results should be treated with caution due to the small number of males who took part. Our findings suggest that hair cortisol may represent a biomarker of exposure to trauma in this age group; however, further study is necessary with a particular focus on the characterization of trauma and other forms of adversity.