Hippocampal volume and white matter impairments in patients with congenital adrenal hyperplasia

CONTEXT: Patients with congenital adrenal hyperplasia (CAH) have life-long imbalances in adrenal hormones that may result in changes in structure and function of the brain, that can impair cognitive performance. The hippocampus might be especially sensitive for cortisol and androgen disturbances but has not been systematically investigated in this patient group. OBJECTIVE: In this study we assessed hippocampal subfield volumes, mean diffusivity, and resting-state functional connectivity along with memory performance in patients with CAH and healthy controls using structural magnetic resonance imaging. DESIGN: Cohort study, patients were recruited and tested as part of the PREDEX study. SETTING: Single research institute. PARTICIPANTS: 29 patients with CAH (20 females, 9 males) and 33 healthy controls (19 females, 14 males). INTERVENTION(S): No intervention was performed. MAIN OUTCOME MEASURE(S): Hippocampal subfield volumes, mean diffusivity, resting-state functional connectivity, and memory performance. RESULTS: Patients with CAH had reduced left CA4 and left and right subiculum volumes. In the group by sex interaction analyses males presented higher mean diffusivity in left CA3 and CA4 compared to controls. When looking at males and females separately, it was identified that females had reduced volumes of the bilateral subiculum, CA1 and left CA3 and CA4. Hippocampal structural alterations were not associated with memory performance. CONCLUSIONS: Patients with CAH had structural alterations in several hippocampal subfield volumes, but there might be a discrepancy between males and females in sensitivity to white or grey matter impairments. The findings warrant further investigation into sex-specific differences in treatment sensitivity to optimize brain health in both men and women with CAH.