Abnormal Brain Spontaneous Activity Of PLN And Hypothalamus-PLN In The First-degree Relatives Of Patients With MDD

Objective: The early detection of individuals with high-risk states for the development of major depressive disorder(MDD)is a frontier in psychiatry research.And a promising approach of identifying biological markers is critical for early detection.In recent years,MDD has been demonstrated to be associated with abnormalities in the prefrontal-limbic network(PLN).There also has been some evidence pointing to that MDD patients showed aberrant functional connectivity between hypothalamus and PLN.However,what remains unclear is whether these changes are also present in healthy individuals with hereditary risk for depression while resting state.This study attempts to explore the functional activities of PLN,the patterns of the functional connectivity between hypothalamus and PLN in first-degree relatives of patients with MDD,and to analyze the relationship between the changes and the severity of subclinical depressive symptoms.Methods: To ensure each group meet the inclusion criteria,All the subjects were screened by the Mini International Neuropsychiatric Interview and the 24-Item Hamilton Depression Rating Scale.Then volunteers in both groups underwent rs-f MRI scanning and completed a set of scales measurement.Moreover,we used the Clinical Interview for Depression(CID)for assessing subclinical depressive symptoms in the high-risk group.The data of the f MRI were processed with the software DPABI and REST:(1)Region of interest(ROI)were defined anatomically corresponding to the different regions of PLN as described in published literature.So the PLN mask were placed in orbitofrontal cortex(OFC),dorsolateral prefrontal cortex(DLPFC),dorsomedial prefrontal cortex,ventromedial prefrontal cortex(vm PFC),hippocampus,amygdala,rostral anterior cingulate cortex,subgenual anterior cingulate cortex(sg ACC).Then using ANOVA analyzed the differences in the fractional amplitude of low-frequency fluctuation(f ALFF),regional homogeneity(Re Ho),Degree centrality(DC)within the mask between the three groups,(2)The paraventricular nuclei of the hypothalamus(PVN)were selected as the ROI to analysis the functional connectivity(FC)with other brain regions of PLN,then the differences in FC between the three groups were tested;(3)For the high-risk group,the correlation of f ALFF,Re Ho,DC and FC respectively with the CID scores were analyzed.Results:(1)Compared with the MDD group and the control group,the high-risk group showed significantly increased Re Ho in sg ACC;compared with the MDD group and the control group,the high-risk group showed significantly decreased DC in left hippocampus;compared with the control group,the MDD group showed significantly increased DC in sg ACC.(2)compared the control group,the high-risk group showed significantly decreased FC in the left PVN and the right DLPFC;compared the control group,the high-risk group showed significantly decreased FC in the right PVN and the right DLPFC while not corrected for multiple comparisons at a cluster level;Compared the control group,the MDD group showed significantly decreased FC in the left PVN and the right DLPFC as well as the left PVN and the left vm PFC;(3)In the high-risk group,significantly negative correlations were found between the CID score and the f ALFF in the bilateral OFC.Conclusion: This is the first study to explore the patterns of brain spontaneous activity of PLN and hypothalamus-PLN in first-degree relatives of patients with MDD combining rs-f MRI and high-risk strategies.Our results suggested:(1)the first-degree relatives of patients showed abnormal functional activity of PLN in resting state,and the spontaneous hyperactivity in the sg ACC and the reduced DC in left hippocampus may be the underling diathesis markers for high-risk individuals;(2)the first-degree relatives of patients showed abnormal functional connections of hypothalamus-PLN,and decreased FC in the right PVN and the right DLPFC may be the underling approximate marker for high-risk individuals;(3)the subclinical symptoms of the first-degree relatives was closely related to the activity in OFC,indicated that the functional abnormality in OFC may be an early warning signal.