Resting-state Functional Connectivity Of The Amygdala In Untreated, First Episode Depression

Background:Major depressive disorder, there are about 0.35 billion patients all over the world, is a common mental disorder. Previous studies have found that depressions onset at different ages have different symptoms and different brain structures and functional changes. Presumably they may have different etiology and pathogenesis. The amygdala is one of the most important brain regions with regard to emotion regulation, especially to negative emotion regulation. Changes in the structure and function of the amygdala in patients with depressive disorder have been confirmed. In this study, we hypothesize that resting-state funcional connectivity of amygdala in untreated, first episode depression has changed compared to the controls, and the changes vary with the age of onset.Methods:85 untreated, first-episode depression patients,under 45 years old, diagnosed with DSM-IV (Diagnostic and Statistical Manual of Mental Disorder, fourth edition) and 85 gender-and age-matched healthy controls were included in this study. All participants were arranged to undergo a functional magnetic resonance imaging (fMRI) scan session in resting-state. In the MATLAB2.0 operating platform, the MRIconvert was used to convert the original image of patients and normal controls from DICOM image into NIFTI format. Left and right amygdala were chosen as region of interest(ROI), and then DPARSF was used to pre-process the image of patients and controls;the time series of ROI were extracted and correlation of time series between ROI and whole brain was analyzed. Tthe data that head moved more than 1.5mm and 1.5 degrees or too much data loss after normalization were removed. Then,74 patients and 82 controls were included in the statistics. According to the age of onset, they were divided into four groups:18～29-years-old patients(early-onset, EO),30～45-years-old patients(later-onset, LO),18～29-years-old healthy controls and 30～45-years-old healthy controls. Used two independent samples t-text, changes in the functional connectivity of amygdala between depression patients and healthy controls were compared,18～29-years-old patients and 18～29-years-old controls,30～45-years-old patients and 30～45-years-old controls,18～29-years-old patients and 30～45-years-old patients.Results:1. In comparison with healthy controls, depressed patients showed increased resting-state functional connectivity between the left amygdala with bilateral frontal lobe(the left inferior frontal gyrus and the right middle frontal gyrus), the ipsilateral temporal lobe(the left middle temporal gyrus),the controlateral posterior cingulated gyrus(the right posterior cingulated gyrus), and decreased resting-state functional connectivity between the left amygdala with bilateral dorsolateral frontal lobe(the left inferior frontal gyrus and the right middle frontal gyrus),the parietal lobe(the left inferior parietal lobule and the right inferior parietal lobule),the ipsilateral hippocampus,the contralateral pons,the insular,the cerebellum(the right cerebellar tonsil and the right cerebellum posterior lobe). They also shows increased resting-state functional connectivity between the right amygdala with bilateral uncus and the contralateral posterior central gyrus, and decreased resting-state functional connectivity between the right amygdala with bilateral dorsolateral frontal(the left inferior frontal gyrus, the left middle frontal gyrus and the right middle frontal gyrus), the ipislateral occipital lobe(the right lingual gyrus),the cerebellum(the right cerebellum uvula and the right cerebellar tonsil),the contralateral parahippocampus,the cerebellum(the left cerebellum posterior lobe). And the functional connectivity between left amygdala and the right insular, the right amygdala and the left parahippocampus was negatively related to the score of Hamilton depression scale(HAMD).2.In comparison with healthy control, early-onset(EO) depressed patients’left amygdala showed increased resting-state functional connectivity with bilateral ventromedial frontal(the left rectal gyrus and the right rectal gyrus),the ipsilateral parahippocampus, and decreased resting-state functional connectivity with ipsilateral dorsolateral frontal lobe(the left inferior frontal gyrus), the parietal lobe(the left inferior parietal lobule), the contralateral parietal lobe(the right precuneus), the cerebellum(the right cerebellar tonsil). And their right amygdala shows increased resting-state functional connectivity with the ipsilateral temporal lobe(the right infrtior temporal gyrus), the thalamus, the contralateral parietal lobe(the left postcentral gyrus), and decreased resting-state functional connectivity with the right insula. The functional connectivity between the left amygdala and the right praecuneus, the right amygdala and the right insular are negatively related to the score of HAMD.3.The later-onset(LO) depressed patients compared with 30～45-years-old healthy controls, their left amygdala showed decreased resting-state functional connectivity with contalateral insular, cerebellum(right cerebellar tonsil). Their right amygdala showed increased resting-state functional connectivity with ipsilateral uncus, pons, contralateral cerebellum(the anterior lobe of left cerebellum), occipital(the left lingual gyrus), and decreased resting-state functional connectivity with bilateral dorsolateral prefrontal(the left inferior frontal and the right middle frontal gyrus), ipsilateral fusiform gyrus, cerebellum(the right cerebullar uvula). The functional connectivity between the left amygdala and the right insular is positively correlated with the score of HAMD, and the functional connectivity between the right amygdala and the left lingual gyrus is negatively correlated with the score of HAMD.4.In comparison with LO depressed patients, the EO depressed patients’left amygdala showed increased resting-state functional connectivity with ipsilateral cerebellum (anterior lobe of left cerebellum and posterior lobe of left cerebellum). And the EO depressed patients’right amygdale showed increased resting-state functional connectivity with ipsilateral insula and decreased resting-state functional connectivity with ipsilateral pons, occipital lobe, precuneus.Conclusions:1. In comparison with healthy controls, the amygdala resting-state functional connectivity of untreated first episode depressed patients was changed, and the abnormal functional connectivity of bilateral amygdala was different. The left amygdala showed increased functional connectivity with frontal lobe, ipsilateral temporal lobe, contralateral posterior cingulate cortex, and decreased functional connectivity with inferior parietal lobule, ipsilateral hippocampus,and cerebellum. The right amygdala showed increased functional connectivity with uncus gyrus, postcentral gyrus, and decreased functional connectivity with frontal lobe, occipital lobe, parahippocampus. The functional connectivity of bilateral may have a tendency to be complementary. Our patients had a short course of disease and had no effects of medicine and chronic disease, so our results may demonstrate that changes in functional connectivuty of the bilateral amygdala may be quality characteristics of depression.2. Compared with the corresponding age of normal controls, depressed patients of different ages showed different characteristics in the changes in functional connectivity of bilateral amygdala. The changes of functional connectivity in EO patients are mainly in the left amygdala,and their left amygdala showed increased functional connectivity of the frontal lobe, parahippocampus, and decreased functional connectivity of the parietal lobe. Changes in the functional connectivity in LO patients are mainly in the right amygdala,and their right amygdala showed increased functional connectivity with occipital and decreased functional connectivity of the frontal lobe.3. Depressed patients of different ages have different characteristics of functional connectivity of the amygdala,demonstrating that depression may have different pathogenesis related to age. It contributes to researching the pathogenesis and classification of depression, which has larger heterogeneity.