Depressed Patients The Resting State Brain Functional Magnetic Resonance Study

BackgroundMajor depressive disorder (MDD) is a common mental disorder, which ischaracterized by persistent depressed mood, anxiety and dysphoria, psychomotorchanges, alterations of motivation and social behavior, and sleep abnormalities. In thelast decades, many studies have advanced our understanding to the pathogenesis ofdepression largely such as cellular studies, animal studies, imaging studies, andneuropsychological studies. Among these, imaging studies should be especiallyemphasized here. Previous imaging studies have showed abnormalities in variousbrain areas and brain networks in depression. It was presumed that there wereabnormality in some brain circuits such as cortico-limbic circuit. But the results werealways different. Also, there are not affirmative results which can be used for clinicaldiagnose and treatment evaluation. In resting state, subjects are not needed tocomplete specific tasks, so it is easy to complete for depressed patients. Moreimportant is, it can reflect the brain function in base state, so has practical advantagesfor basic study and clinical application. But to our knowledge, studies aboutdepression using resting-state fMRI are seldom. In the present study, we used fMRI,regional homogeneity and functional connectivity as methods for data analysis, toinvestigate the patten of brain activity of depressed patients, and further to observe theinfluence of antidepressant drug to the brain activity of depressed patients, therebyoffer more information to the understanding of the pathogenesis of depression.Experiment 1: The change of regional brain function of depressed patients.Objective: Using a newly reported regional homogeneity (ReHo) approach, we are toexplore the features of brain activity of patients with major depressive disorder (MDD)during resting state, and further to examine the relationships between abnormal brain activity of depressed patients and each of the clinical variables, including duration ofillness, number of episode, total depressive severity, and specific symptom clustersseverity, then observe the influence of gender to brain function of depressed patients.Methods: 61 patients with MDD and 33 healthy subjects participated in the resting-state fMRI scans. Among these, 48 depressed patients(depressed group) and 25healthy controls(normal group) whose imaging data satisfy the criteria of thisexperiment and clinical data are intact were analysed. Then as gender, all subjectswere divided into four groups, that are, 23 men depressed patients (men depressedgroup), 25 women depressed patients (women depressed group) and 11 men normalcontrols (men normal group), 14 women normal controls (women normal group).Using ReHo approach, ReHo maps of each subjects were produced. To explore theReHo differences between depressed group and normal group, men depressed groupand men normal group, women depressed group and women normal group, mendepressed group and women depressed group, men normal group and women normalgroup, two-sample t-tests was performed on the individual normalized ReHo maps ina voxel-by-voxel manner using SPM software. A combined threshold of P<0.005 anda minimum cluster size of 270mm3 (10 voxels) were used to determine significantdifferences. Using marsbar software, mean ReHo values of the clusters which hadshown differences between depressed group and normal group were extracted. Finally,using SPSS software, multiple regression analysis was performed to measure therelationships between those mean ReHo values and duration of illness, number ofepisodes, total depressive severity, and specific symptom clusters severity. P<0.05was used to determine significant correlation.Results:1. The depressed group showed significant ReHo increase in the left orbitofrontalcortex, the right angular gyrus, the right fusiform gyrus, the right inferior parietal lobule, and the bilateral precuneus, and significant ReHo decrease in the rightdorsolateral prefrontal cortex, the left superior temporal gyrus, the left middletemporal gyrus, the right posterior cingulate gyrus, the left insula, the left caudate,and the left lentiform.2. In depressed patients, ReHo value in the left orbitofrontal cortex was positivelycorrelated with retardation severity(P=0.016). ReHo value in the right Angular gyruswas positively correlated with total depressive severity, cognitive disturbance severity,retardation severity, and sleep disturbance severity (P=0.003,0.034,0.048,0.007).ReHo value in the right dorsolateral prefrontal cortex was positively correlated withweight loss severity, retardation severity (P=0.007,0.021). ReHo value in the leftsuperior temporal gyrus was positively correlated with number of episode (P=0.006).3. Compared with men normal group, the men depressed group showed significantlyincreased ReHo in the right precentral gyrus and the right fusiform gyrus,significantly decreased ReHo in the bilateral medial frontal gyrus. Compared withwomen normal group, the women depressed group showed significantly increasedReHo in the left lingual gyrus, the right orbitofrontal cortex, the right medial frontalgyrus, the right posterior cingulate and the right precuneus, decreased ReHo in theright precentral gyrus, the left fusiform gyrus, the left dorsal anterior cingulate, theleft lentiform, the left claustrum and the left insula. Compared with womendepressed group, the men depressed group showed significantly increased ReHo inthe left middle temporal gyrus, the left dorsal anterior cingulate, the bilateral insulaand the bilateral claustrum, decreased ReHo in the right superior frontal gyrus andthe left posterior cingulate. Compared with women normal group, the men normalgroup showed significantly increased ReHo in the bilateral medial frontal gyrus, theleft inferior temporal gyrus and the left thalamus, decreased ReHo in the superiortemporal gyrus, the left inferior parietal lobule, the right thalamus and the left parahippocampal gyrus.Conclusion: This study testified functional abnormality existed in frontal lobe,temporal lobe, parietal lobe, cingulate gyrus, insula and basal ganglia in depressedpatients, some brain regions were correlated with specific clinical features. Genderdifferences exist in the brain activity of depressed patients, and gender should beconsidered in related studies in future.Experiment 2: The change of brain function in network level in depressedpatients.Objective: Through observing resting-state functional connectivity patterns ofhippocampus in subjects with recurent MDD, we were to supply more evidences forthe neural mechanisms underlying dysfunction of episodic memory in depression.Methods: 16 recurrent patients with MDD and 16 gender-, age-, and education-matched healthy subjects were selected from experiment 1, they images after band-pass filtering and linear trend removing were analysed. Pearson's correlation analysiswas carried out between the reference time course of hippocampus and the rest of thewhole brain in a voxel-wise way. Finally, functional connectivity maps for eachsubjects were produced. Two-sample t-test was applied on the functional connectivitymaps of the two groups. A combined threshold of P<0.005 and a minimum clustersize of 270mm3 (10 voxels) were used to determine significant differences.Results: Compared with healthy group, the left hippocampus exhibited increasedfunctional connectivities with the right inferior frontal gyrus and the right subgenualcingulate, but decreased functional connectivities with the left superior frontal gyrus,the right precuneus and the left fusiform gyrus in depressed group. Right hippocampus exhibited decreased functional connectivities with the rightdorsolateral prefrontal cortex, the left medial frontal gyrus, the right precuneus, theleft inferior parietal lobule, the left parahippocampal gyrus and the left insula indepressed group.Conclusion: Functional connectivity pattens of hippocampus were disrupted indepressed patients during resting state, which indicated abnormality existed inhippocampus-related memory network in depressed patients, and other functionalnetworks might effect on it.Experiment 3: Effect of antidepressant drug treatment on the brain function ofdepressed patientsObjective: This study was to examine the effect of antidepressant drug treatment onthe brain function of depressed patients.Methods: In the basis of experiment 1, 27 depressed patients were perfomed thesecond scans after eight-week antidepressant drug treatment. Among them, the data of20 patients satisfied the criteria of this experiment. 20 gender-, age-, and education-matched healthy controls were selected from experiment 1 as control group. UsingSPM software, paried t-test was performed in pre- and pro- treatment group, twosample t-test was performed in pretreatment group and control group, protreatmentgroup and control group. A combined threshold of P<0.005 and a minimum clustersize of 270mm3 (10 voxels) were used to determine significant differences.Results: Compared to healthy controls, pretreatment depressed group showedsignificantly increased ReHo in the left posterior cingulate (BA31), decreased ReHoin the left inferior frontal gyrus, the right superior temporal gyrus, the left posteriorcingulate (BA29), the left lentiform and the right caudate. Compared to pretreatment, depressed group showed significantly decreased ReHo in the bilateral middle frontalgyrus, the left dorsal anterior cingulate, left insula, increased ReHo in the leftsuperior frontal gyrus, the right superior temporal gyrus and the left precuneus aftertreatment. Compared to healthy controls, protreatment depressed group showedsignificantly increased ReHo in the left superior temporal gyrus, the right fusiformgyrus and the bilateral thalamus.Conclusions: There are dysfunction in many brain regions and systems in depressedpatients. After effective antidepressant treatment, some can improve, but some stillexist, this may revealed the lag of brain functional improvement or durativedepressive trait.