Effects of Hormones and Sex Chromosomes on Stress‐Influenced Regions of the Developing Pediatric Brain

Abstract

Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus suggests that biological factors 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 children 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.

Klinefelter’s Syndrome: A Clinical and Therapeutical Update

“…The neural mechanisms underlying the cognitive/behavioral phenotype of Klinefelter patients have been studied by several authors with both structural and neuroimaging methods. A reduced total brain volume in Klinefelter patients has been reported by several authors using magnetic resonance imaging (MRI) [Shen et al, 2004;DeLisi et al, 2005;Giedd et al, 2007], even though this finding was not confirmed by other authors [Patwardhan et al, 2000[Patwardhan et al, , 2002Rose et al, 2004]. The volume of specific cerebral regions involved in different abilities (language, verbal memory, executive function, and social processes) was also studied.…”

Sex as a Biological Variable: Who, What, When, Why, and How

“…Neuroimaging studies comparing children in early puberty with Turner syndrome (XO) and Klinefelter's syndrome (XXY) to agematched controls, indicate a dose-dependency of the X chromosome to decreased parieto-occipital and increased temporo-insular gray matter volumes Hong and Reiss, 2014). A similar study also reported smaller hippocampal volumes in XXY boys compared with agematched controls (Rose et al, 2004). Interestingly, XYY karyotypes that do not present with a detectable phenotype have normal behavior and cognitive abilities, and normal serum testosterone levels, suggesting that, although the dosage of X-linked genes is important in normal development, this may not be the case for Y-linked genes.…”

The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

“…Moreover, women who experienced early life stress are more likely to develop depression as well as IBS (Bradford, et al 2012). Sexhormones influence amygdala development in human populations (Rose, et al 2004). An alteration in the central CRF system has been evidenced in two different rat models of comorbid depression and functional GI disorders (e.g.…”