Increased medial temporal lobe and striatal grey-matter volume in a rare disorder of androgen excess: a voxel-based morphometry (VBM) study

Major questions remain about how sex hormones influence human brain development and cognition. Studies in humans and animals suggest a strong impact of androgen on the structure and function of the medial temporal lobe (MTL) and striatum. Using voxel-based morphometry (DARTEL), we compared MTL and striatal structures in 13 [ mean age (+/- S.D.) 12.7 +/- 3.2 yr, mean bone age 14.8 +/- 3.2 yr] boys with familial male precocious puberty (FMPP), characterized by early excess androgen secretion, and 39 healthy age-matched boys (mean age 14.3 +/- 2.5 yr). The FMPP group showed significantly larger grey-matter volume (GMV) in parahippocampal and fusiform gyri as well as putamen relative to controls. By comparison, larger GMV for controls relative to patients was only apparent in the precentral gyrus. Exploratory regression analyses that examined the impact of age on the current findings revealed a significant increase of GMV in the putamen with age in patients suffering from excess androgen but not in controls. Finally, current levels of free testosterone were obtained in the patient group. Analyses revealed a significant negative association indicating that FMPP boys with low levels of bioavailable testosterone exhibited high GMV in the bilateral striatum. The findings suggest a critical influence of androgen on human brain development and are discussed in relation to male-dominant psychiatric childhood disorders.