SEX DIFFERENCES AND THE EFFECTS OF SEX HORMONES ON THE STRUCTURE OF THE CORPUS CALLOSUM

OBJECTIVE This thesis examines sex differences in the structural properties of the corpus callosum (CC) during adolescence and investigates the possible role of sex hormones in the development of these sex differences, as well as hormonal effects on the inter-individual variations in the structure of the CC in young women. DESIGN This thesis is conducted on three separate study samples: 1) the Saguenay Youth Study (SYS) sample (n=737); 2) the IMAGEN Study sample (n=1,979); and 3) the Cycle Study sample (n=26). The SYS and IMAGEN studies are large-scale studies carried out with magnetic resonance imaging (MRI) in typically developing adolescents from Canada (12 to 18 years) and Europe (13 to 15 years), respectively. In these studies, the “sex hormone-CC” relationship is explored by examining the association between the CC and: testosterone level, duration of sex hormone exposure (since menarche), puberty stage and contraceptive use. The Cycle study examines the CC of 13 freely cycling and 13 oral contraceptives (OCP) using young women (18 to 30 years) scanned using MRI across four separate phases of their menstrual cycle. Freesurfer-based computational anatomy is used to estimate the volume of the total corpus callosum and its segments in all three studies. Magnetization transfer imaging (MTI) is used to assess microstructural properties of the corpus callosum in the Cycle study. RESULTS The relative volume of the corpus callosum is seen to be sexually dimorphic in both the SYS and IMAGEN adolescents with a female versus male advantage that is particularly significant for the anterior, central and posterior segment of the corpus callosum; the mid-anterior segment is larger in males versus females. Pubertal stage of adolescent boys (SYS) demonstrates a negative correlation with the relative volume of the anterior CC and a positive correlation with the relative volume of the mid-anterior CC. These associations are consistent with the sex differences observed (anterior: F>M; mid-anterior: M>F), thus suggesting that male sex hormones that are responsible for inducing pubertal development of boys may play a role in generating the sexually dimorphic volume of the corpus callosum in a region-specific manner. Contraceptive use in adolescent girls (SYS and IMAGEN) is negatively associated with the relative volume of the corpus callosum. In addition, the Cycle study demonstrates a trend for lower MTR values in women using contraceptives versus freely cycling women, thus suggesting that the natural sex steroids suppressed by use of oral contraceptives may exert a positive effect on the volume of the CC, possibly by increasing the degree of myelination. The Cycle study demonstrates an increase in the relative volume of the total corpus callosum of freely cycling women from the ovulatory to the luteal phase with corresponding decreases in the MTR value of the total CC. This finding suggests that increased production of progesterone during the luteal phase may cause an increase in the relative volume of the CC, possibly by increasing the axonal calibre. CONCLUSION Sex steroids influence the structure (relative volume and MTR) of the corpus callosum.