Menstrual Cycle-Related Changes in Women with Schizophrenia: A Resting-State fMRI Study

Introduction: Different influences of ovarian hormones in schizophrenia (SCZ) have been reported, but no study to date has assessed their effects on the brain dynamics at rest. The present study aimed to examine the hormonal and clinical changes related to the menstrual cycle and alterations in the resting-state functional connectivity (RS-FC) depending on cycle phase and/or hormonal fluctuations in SCZ. Method: This study was conducted based on both between- and within-subject experimental designs, including 13 clinically stable female patients with SCZ (32 ± 7.7 years) and 13 healthy women (30 ± 7.3 years). RS-functional magnetic resonance imaging (fMRI) scanning, as well as hormonal and clinical assessments, was applied to each participant twice during two cycle phases: early follicular and mid-luteal. Results: A difference in mid-luteal progesterone levels was found between groups, with a large effect size (Cohen’s d) of 0.8 (p < 0.05). Also, the estradiol levels negatively correlated with the negative symptom severity of the patients during their mid-luteal phase. In the patients, estrogen positively correlated with the auditory network connectivity in the left amygdala during the early follicular phase. In the controls, progesterone had positive correlations with the connectivity of the posterior default mode and the left frontoparietal networks in the bilateral precuneus during the early follicular phase and had a negative correlation with the executive control network connectivity in the mid-luteal phase. Conclusion: The present study showed hormonal differences between groups and suggested that the levels of cycle-dependent hormones might be associated with the changes in clinical symptom severity and the RS-FC in the groups. Our RS-fMRI findings warrant further investigation.