Sex Differences in White Matter Microstructure in the Human Brain Predominantly Reflect Differences in Sex Hormone...

Area of Science:

• Neuroscience
• Endocrinology
• Human Genetics

Background:

• Sex differences in human brain morphology are established but underlying mechanisms remain unclear.
• Complete androgen insensitivity syndrome (CAIS) in 46,XY individuals provides a unique model to study isolated sex hormone effects on neural development.

Purpose of the Study:

• To investigate the role of sex hormones in the sexual differentiation of white matter (WM) microstructure.
• To compare WM microstructure in women with CAIS, comparison men, and comparison women using diffusion tensor imaging.

Main Methods:

• Diffusion tensor imaging (DTI) was employed to assess white matter microstructure.
• Fractional anisotropy (FA) and radial diffusivity were analyzed in three groups: 46,XY women with CAIS (n=20), 46,XY men (n=30), and 46,XX women (n=30).

Main Results:

• Significant sex differences in FA were observed, with men typically showing higher FA than women.
• Women with CAIS displayed FA values consistent with typical female patterns across extensive WM regions.
• This female-typical pattern in CAIS was primarily driven by radial diffusivity.

Conclusions:

• Sex hormones play a predominant role in the sexual differentiation of white matter microstructure.
• While hormones are key, sex chromosome genes and androgen effects independent of the androgen receptor may also contribute to neural sexual differentiation.