Functional Magnetic Resonance Imaging Study On Emotional And Verbal Fluency In College Students With Sub-Clinical Depression

ObjectiveSub-clinical depression,also known as sub-threshold depression(St D),refers to a state that patients have developed certain depressive symptoms but do not meet the diagnostic criteria for major depressive disorder(MDD),which is considered a transitional stage of MDD.In China,about 25% of college students suffer from depression,mostly sub-clinical depression.Long-standing sub-clinical depression may deteriorate into MDD,and lead to suicide.There are few brain imaging studies on the neurobiology of sub-clinical depression,and its potential neurobiological mechanism is unclear.Therefore,in-depth studies of sub-clinical depression in college students are of great significance for the understanding of the process of depression,prediction of depression,and early intervention for depression.MethodsIn this study,106 subjects were recruited in total,including 57 patients with sub-clinical depression(20 males and 37 females)and 49 healthy subjects(13 males and 36females).Subjects in the two groups were matched in age,sex,and education level,and all the subjects were right-handed.Patients with sub-clinical depression were diagnosed by professional psychologists,and the severity of the disease was judged by 17 items of the Hamilton Depression scale(HAMD-17)and Beck Depression Inventory(BDI).The verbal fluency of all subjects was judged by their scores in the Verbal Fluency Test(VFT),and their emotional state was evaluated with the State-trait anxiety inventory(STAI).German Siemens MAGNETOM＿Prisma3.0T magnetic resonance imaging scanner is applied in this study to collect functional image data of all subjects in resting state.Image preprocessing was performed using SPM12(www.fil.ion.ucl.ac.uk/spm)and DPARSF version 2.3(http://rfmri.org/ DPARSF).The processing steps include:(1)DICOM-NIFTI format conversion(2)removal of the first 10 time points(3)realignment(4)spatial normalization(5)spatial smoothing(6)removal of linear detrends(7)nuisance regression(8)filter(0.01～0.08hz).Twenty-seven regions of interest(ROI)including the default mode network(DMN),central executive network(CEN),salience network(SN),and limbic system(LS)were selected as seeds for functional connectivity(FC)analyses.Coordinates(the detailed ROI definition seen in Table 1)were considered as a center of ROI with a5 mm radius.The brain regions with differences were obtained by a two-sample T-test with SPM software.Then we extract the FC values of different brain regions by REST software and analyze the correlation with the clinical indexes.This study was approved by the medical ethics committee,and all subjects had signed the informed consent for MR examination before participating in this study.Results1.The differences of general data and clinical scaleThere was no significant difference between the two groups in terms of sex(P =0.343),age(P = 0.563)and education(P = 0.154).The scores of STAI＿trait(trait anxiety)and STAI＿state(state anxiety)in the subclinical depression group were higher than those in the healthy control group(P < 0.001 and P < 0.001).There was no significant difference in the scores of VFT＿animal(semantic VFT)and VFT＿fa(phonemic VFT)between the two groups.2.Differences in functional connectivity between the two groupsTaking gender,age,and education as covariables,after cluster-level FWE correction,there were significant differences in the functional connectivity of 5 ROI between the subclinical depression group and the healthy control group.compared with the healthy control group,the functional connectivity between the left lateral parietal cortex and the right postcentral gyrus and the right inferior parietal gyrus was enhanced in the sub-clinical depression group.The functional connectivity between the left insular and the left orbital inferior frontal gyrus,bilateral deltoid triangular part of inferior frontal gyrus and left cuneus was enhanced;the functional connectivity between the left subgenual anterior cingulate cortex and bilateral supplementary motor area,bilateral median cingulate,and paracingulate gyrus brain regions was enhanced;the functional connectivity between the right subgenual anterior cingulate cortex and bilateral supplementary motor areas,bilateral median cingulate and paracingulate gyrus regions was enhanced.The functional connectivity between the left ventral hippocampus and the right triangular part of the inferior frontal gyrus and the right opercular part of the inferior frontal gyrus was enhanced.The brain regions with abnormal functional connectivity were generally characterized by enhanced functional connectivity,and no brain regions with decreased functional connectivity were found.3.Correlations Between Altered Functional Connectivity and Clinical ScoresUsing partial correlation analysis,it was found that in patients with subclinical depression,the functional connectivity between the left insular and the left orbital inferior frontal gyrus,bilateral deltoid triangular part of inferior frontal gyrus was positively correlated with the STAI＿trait score(r=0.3,P = 0.028),while the functional connectivity between the left insular and the left cuneus was positively correlated with the STAI＿trait score(r=0.283,P=0.038).The functional connectivity between the right subgenual anterior cingulate cortex and bilateral supplementary motor area,bilateral median cingulate and paracingulate gyrus were positively correlated with STAI＿trait scores(r= 0.328 P=0.015).Although there was no difference in VFT＿fa scores between the two groups,we still found that VFT＿fa scores were positively correlated with the functional connectivity between the left subgenual anterior cingulate cortex and bilateral supplementary motor areas,bilateral median cingulate and paracingulate gyrus(r=0.367 P=0.006),and positively correlated with the functional connectivity of the right subgenual anterior cingulate cortex and bilateral supplementary motor areas,bilateral median cingulate and paracingulate gyrus(r=0.355,P=0.008).Besides,there were significant differences in BDI and STAI＿state scores between the two groups.However,no correlation was found between BDI,STAI＿state,VFT＿animal scores and functional connectivity.Conclusion1.The abnormality of multiple brain networks in patients with sub-clinical depression reveals the possible neural mechanism of sub-clinical depression,and it is speculated that sub-clinical patients with depression have disorders of self-attention,somatosensory,emotional regulation,and executive function.2.The abnormal functional connectivity between the left insular and the right subgenual anterior cingulate cortex was positively correlated with negative emotion,and the functional connectivity between bilateral subgenual anterior cingulate cortex was positively correlated with cognitive-related phonemic fluency.it is suggested that there is a wide range of abnormal functional connectivity in emotion and cognition-related brain regions in patients with subclinical depression.3.The abnormal functional connectivity between lateral parietal cortex,left insula,bilateral subgenual anterior cingulate cortex,and left ventral hippocampus may be the neurobiological basis of subclinical depression,which can provide an objective basis for the prediction of depression.