The resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women

Objective This study aimed to investigate the resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women. Methods Total 66 perimenopausal women voluntarily participated in this study from October 2012 to June 2013.Zung Self-rating Depression Scale (ZSDS) was used to assess depression symptoms.Plasma gonadal steroid hormones including estradiol, testosterone, and progesterone were determined by the chemiluminescence immunoassay.A 3.0 Tesla magnetic resonance imaging (MRI) scanner was utilized to acquire resting-state functional MRI data.The z-value functional connectivity map of each participant was calculated voxel-wisely based on the seed region of the hypothalamus.One sample t test of Statistical Parametric Mapping (SPM) were used to determine the brain areas with statistically significant functional connectivity to the hypothalamus, then multiple regression of SPM was used to calculate the correlated areas with 3 gonadal steroid hormones, respectively.Finally, Pearson correlation was performed to analyze bivariate correlations between mean z-values and ZSDS scores. Results Significant functional connectivity to the hypothalamus were found in brain areas as follows: the lateral inferior frontal gyrus, medial prefrontal cortex, dorsal lateral prefrontal cortex, orbitofrontal cortex, subgenual cortex, anterior cingulate cortex, posterior cingulate cortex, cuneus and precuneus, hippocampus and parahippocampal gyrus, and angular gyrus (False Discovery Rate q<0.05). Among these areas, the plasma testosterone level was positively related to the functional connectivity strength of the right angular gyrus, and negatively related to the strengths of the right subgenual cortex and bilateral medial superior frontal gyrus to the hypothalamus (PAlphaSim<0.05). Especially, mean z-value in the subgenual cortex was positively related to the ZSDS index score (r=0.279, P=0.023), and factor scores of the core depression symptoms (r=0.278, P=0.024) and somatic symptoms (r=0.357, P=0.003). Conclusion In perimenopausal women, the hypothalamus has resting-state functional connectivity with widespread areas involved in the brain depression-related network and default mode network, and the plasma androgen level may modulate the functional connectivity strengths of the hypothalamus and decrease the susceptibility of perimenopausal women to depression. Key words: Depressive disorders; Disease susceptibility; Menopause; Neuroimaging; Ageing