Effects of Congenital Adrenal Hyperplasia (CAH) and Biological Sex on Brain Size

Congenital Adrenal Hyperplasia (CAH) has been reported to involve structural alterations in some brain regions. However, it remains to be established whether there is also an impact on the size of the brain as a whole. Here, we compiled the largest CAH sample to date (n = 53), matched pair-wise to a control group (n = 53) on sex, age, and verbal intelligence. Using T1-weighted brain scans, we calculated intracranial volume (ICV) as well as total brain volume (TBV), which are both common estimates for brain size. The statistical analysis was performed using a general linear model assessing the effects of CAH (CAH vs. controls), sex (women vs. men), and any CAH-by-sex interaction. The outcomes were comparable for ICV and TBV, i.e., there was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex, with larger ICVs and TBVs in men than in women. Our findings contribute to an understudied field of research exploring brain anatomy in CAH. In contrast to some existing studies suggesting a smaller brain size in CAH, we did not observe such an effect. In other words, ICV and TBV in women and men with CAH did not differ significantly from those in controls. Notwithstanding, we observed the well-known sex difference in brain size (12.69% for ICV and 12.50% for TBV), with larger volumes in men than in women, which is in agreement with the existing literature.