231 Ann. N.Y. Acad. Sci. 1032: 231–233 (2004). © 2004 New York Academy of Sciences. doi: 10.1196/annals.1314.027 Effects of Hormones and Sex Chromosomes on Stress-Influenced Regions of the Developing Pediatric Brain A. BLYTHE ROSE, DEBORAH P. MERKE, LIV S. CLASEN, MICHAEL A. ROSENTHAL, GREGORY L. WALLACE, A. CATHERINE VAITUZIS, JEREMY D. FIELDS, AND JAY N. GIEDD National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA ABSTRACT: Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus suggests that biological fac- tors may account for many of the sex differences in stress reactivity. In this study, we have relied on studies of naturally occurring anomalous processes, such as congenital adrenal hyperplasia (CAH) and Klinefelter’s syndrome (XXY), to observe the effects of hormones and sex chromosomes on brain structures thought to influence an individual’s vulnerability to stress. Brain magnetic resonance imaging (MRI) scans were obtained both from 16 boys with classic CAH and 34 age- and sex-matched controls and from 20 XXY chil- dren and 40 age-matched controls. Smaller amygdala volumes were observed in boys with CAH than in matched controls, and in XXY patients than in matched controls. XXY patients were also found to have smaller hippocampus volumes when compared with matched controls. Acknowledging that hormone and sex chromosome effects upon the developing human brain are widespread and complex, it is difficult to conclude, with any certainty, the etiology of the differences found in this study. Future studies that examine longitudinal data and/or other diagnostic groups, however, may help to better elucidate specific hormone and sex chromosome effects upon stress-related structures in the brain. KEYWORDS: hormones; sex chromosomes; stress; pediatric brain INTRODUCTION Males and females have often been shown to react differently to the same envi- ronment, but how much of that difference is attributable to environmental versus biological factors is a matter of debate. Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus (both structures known to have many androgen and glucocorticoid receptors) suggests that Address for correspondence: Jay N. Giedd, National Institute of Mental Health, National Institutes of Health, Bldg. 10, Rm 4C110, 10 Center Drive, Bethesda, MD 20892. Voice: 301- 435-4517. jgiedd@mail.nih.gov