title: Associations between dehydroepiandrosterone (DHEA) levels, pituitary volume, and social anxiety in children.
abstract: 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.
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton, Victoria 3053, Australia; Neuroscience Research Australia, Barker Street, Randwick, New South Wales 2031, Australia.
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Murray
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton, Victoria 3053, Australia; Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia; Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia.
authors.forename: Julian G
authors.initials: JG
authors.lastname: Simmons
authors.affiliation: Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Psychology, University of Oregon, 1715 Franklin Boulevard, Eugene, OR 97403, USA.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Allen
authors.affiliation: Department of Psychology, University of Oregon, 1715 Franklin Boulevard, Eugene, OR 97403, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Byrne
authors.affiliation: Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia; Centre for Adolescent Health, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, 50 Flemington Road, Parkville, Victoria 3052, Australia.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Mundy
authors.affiliation: Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia.
authors.forename: Marc L
authors.initials: ML
authors.lastname: Seal
authors.affiliation: Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia; Centre for Adolescent Health, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, 50 Flemington Road, Parkville, Victoria 3052, Australia.
authors.forename: George C
authors.initials: GC
authors.lastname: Patton
authors.affiliation: Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, 50 Flemington Road, Parkville, Victoria 3052, Australia; School of Psychology, Deakin University, 221 Burwood Highway, Burwood, Victoria 3125, Australia.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Olsson
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton, Victoria 3053, Australia; Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: swhittle@unimelb.edu.au.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whittle
mesh_terms: D050499:Adrenarche / Q000378:metabolism* / Q000523:psychology*; D001007:Anxiety / Q000175:diagnosis / Q000378:metabolism*; D015992:Body Mass Index; D002648:Child; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005260:Female; D006197:Hair / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D000072861:Phobia, Social / Q000175:diagnosis / Q000378:metabolism*; D010902:Pituitary Gland / Q000033:anatomy & histology* / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism
chemical_list: D013739:Testosterone; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone
keywords: Adrenarche; Dehydroepiandrosterone; HPA axis; Pituitary gland; Puberty; Social anxiety