Neural Activity Correlates Of Hypothalamus And Prefrontal-limbic Network In Patients With Major Depressive Disorder:a Resting- State FMRI Study

Objective:In the exploration of the pathogenesis of major depressive disorder (MDD), there has been some evidence pointing to the abnormalities in the hypothalamus, and also in the prefrontal-limbic network (PLN). However, it is not fully understood how these abnormal changes within hypothalamus and PLN are related to each other, and how these changes are related to the severity of depressive symptoms. This study attempts to explore the functional activities between hypothalamus and PLN in patients with MDD, and to analyze the relationship between the changes and the severity of depressive symptoms.Methods:Both MDD patients and matched controls were recruited from the local community. All the volunteers were screened by the Mini International Neuropsychiatric Interview (M.N.N.I.) and the 24-Item Hamilton Depression Rating Scale (HAMD-24), and those who met the inclusion criteria for each group were included in the study. Subjects in both groups underwent rs-fMRI scanning, LES and WCCL measurement. The posterior cingulate cortex (PCC) and the lateral hypothalamic nuclei were selected respectively as the region of interest (ROI) to make the functional connectivity (FC) analysis with other brain regions, then the differences in FC between the two groups were tested; The changes of amplitude of low-frequency fluctuation (ALFF) in the local brain regions of the hypothalamus and the PLN network were analyzed and the differences in ALFF between the two groups were tested; For MDD patients, the correlation of FC index and ALFF index respectively with the HAMD-24 scores were analyzed.Results:1). A comparison of the differences in the default mode network (DMN) between the two groups showed that the connection between PCC and other brain regions was significantly decreased in MDD patients, indicating that the data collected in this study by using a specific scanning sequence of rs-fMRI could be used to detect the neural activities of hypothalamus and PLN in MDD patients; 2). The FC between the lateral hypothalamus and the middle frontal gyrus, medial superior frontal gyrus, and ACC in the PLN were significantly decreased, and the FC between the lateral hypothalamus and PCC, cuneus in DMN were also significantly decreased. Significant positive correlations were found between the HAMD-24 score and the FC of some regions in the PLN (such as the superior frontal gyrus, the medial superior frontal gyrus, the middle frontal gyrus etc.) and the lateral hypothalamic nuclei.3). Compared with the healthy controls, the ALFF value of MDD had significantly increased in the PLN (such as the superior and inferior frontal gyrus, the middle frontal gyrus etc.). Significant positive correlations were also found between the HAMD-24 score and the ALFF value of the left superior frontal gyrus, the left medial frontal gyrus etc. in the PLN. The intensity of spontaneous activity in the paraventricular nucleus within hypothalamus was increased in MDD patients than in healthy controls.Conclusion:These results indicate that there are abnormal changes in functional neural activity not only within hypothalamus and PLN but also between them, and these changes correlate with the severity of depressive symptoms. Findings from this study suggest that the abnormalities between the hypothalamus and PLN may be closely related to the occurrence and development of MDD.