Neuroimaging Studies Of First-episode Drug-naive Adult Major Depressive Disorder Patients With Different Age-onset

Major depressive disorder(MDD)is an affective disorder which pathogenesis relate to genetic factors,environmental factors and psychological stress.These factors contributed to depression via different ways.However,so many studies cannot find a reliable diagnostic biomarker of MDD due to the heterogeneity and comprehensive of MDD.For decades,the neuroimage study has been widely used in detecting pathomechanism of MDD,and obtained some common results which supplied some evidence of pathogenesis in MDD.The clinical features,genetic evidence together with a little bit of neuroimaing evidence suggested the MDD with different age-onset might be subtypes of depression and related to different pathogenesis.However,the cut-off age of these findings were inconsistent.On the other side,the antidepressant using,current episode and illness duration can influence the brain structure and function of MDD.Therefore,identify the neuroimaing alterations in first-episode and drug-naive patients with MDD could supply neuroiamge evidence relate to the potential mechanism of MDD.We used magnetic resonance imaging(MRI)to identify whether the brain grey matter volume changes,the regional functional and the functional connectivity alterations were different in different age-onset adult depression,these alterations might reflect different pathomechanism between early adult onset depression(EOD)and later adult onset depression(LOD).Part ? Changes of grey matter volume in first-episode drug-naive adult major depressive disorder patients with different age-onsetObjective:Little is known about the pathological mechanism of EOD and LOD.We seek to determine whether grey matter volume(GMV)change in EOD and LOD are different,which could also delineate EOD and LOD.Methods:In present study,147 first-episode,drug-naive patients with major depressive disorder,age between 18-45,were divided into two groups on the basis of age of MDD onset:the early adult onset group(age 18-29)and the later adult onset group(age 30-44),and a total of 130 gender-,and age-,matched healthy controls(HC)were also divided into two groups which fit for each patient group.Magnetic resonance imaging was conducted on all subjects.The voxel-based morphometry(VBM)approach was employed to analyze the images.Results:Widespread abnormalities of GMV throughout parietal,temporal,limbic regions,occipital cortex and cerebellum were observed in MDD patients.Compare to young HC,reduced GMV in right fusiform gyrus,right middle temporal gyrus,vermis ? and increased GMV in right middle occipital gyrus were seen in the EOD group.In contrast,relative to old HC,decreased GMV in the right hippocampus and increased GMV in the left middle temporal gyrus were observed in the LOD group.Compared to the LOD group,the EOD group had smaller GMV in right posterior cingulate cortex.There was no significant correlation between GMV of the right posterior cingulate cortex and the score of the depression rating scale in patients group.Conclusion:The GMV of the brain areas that were related to mood regulation was decreased in the first-episode,drug-naive adult patients with MDD.Adult patients with EOD and LOD exhibited different GMV changes relative to each age-matched comparison group,suggesting depressed adult patients with different age-onset might have different pathological mechanism.Part II Identify changes of brain regional homogeneity in early adult and later adult onset patients with first-episode depression using resting-state fMRIObjective:Previous work exhibited different brain grey matter volume(GMV)changes between patients with early adult onset depression(EOD)and later adult onset depression(LOD)by using 30-year-old as the cut-off age.Previous study also suggested brain functional and anatomical change might contributed independently to pathomechanism of MDD.To identify whether regional homogeneity(ReHo)changes are also different between EOD and LOD by using same cut-off age,we using resting-state functional magnetic resonance imaging(fMRI)to detect the abnormal ReHo between patients with EOD and LOD in the present study.Methods:Resting-sate fMRI scans of fifty-eight patients with EOD,sixty-two patients with LOD,sixty young healthy controls(HC),and fifty-two old HC were obtained.ReHo approach was used to analyze the images.Results:The ANOVA analysis revealed the ReHo value in right anterior cingulate and the frontoparietal region were significantly different among the four groups.Relative to patients with LOD,patients with EOD displayed significantly increased ReHo in the left precuneus,and decreased ReHo in the right fusiform.Compared to young HC,patients with EOD showed significantly increased ReHo in the right calcarine gyrus,and right frontoparietal region.Further,the increased ReHo in right frontoparietal region was observed in patients with LOD when compare to old HC.The ReHo value in the left precuneus and the right fusiform had no significant correlation with the score of the depression rating scale or illness duration in both patient subgroups.Conclusion:Abnormal ReHo value alterations in precuneus and fusiform may be the appropriate brain regions to distinguish EOD from LOD,which also suggesting depressed adult patients with different age-onset might have different pathogenesis of depression.Further,ReHo abnormalities in right frontoparietal regions might be the appropriate brain regions to distinguish MDD from HC independent of onset age.Part ? Abnormal functional connectivity between early adult and later adult onset patients with first episode depressionObjective:The ReHo alterlation in precuneus(PCu)and changes of GMV in the posterior cingulate cortex(PCC)were different between patients with EOD and those with LOD in prior study.The PCC/PCu is the key region of the posterior part of the default mode network(DMN).Therefore,the PCu was defined as the region of interest(ROI)to explore whether the functional connectivity(FC)alterlations were different between the patients with EOD and those with LOD,and might relate to different pathogensis of MDD.Methods:The preprocessing resting-state fMRI data were acquired from the part?,fifty-eight patients with EOD,sixty-two patients with LOD,sixty young healthy controls(HC),and fifty-two old HC were finally entered into secondary analysis after discard the patients which had excessive head motion(shift>1.5mm and rotation>1.5°).The left precuneus was selected as seed region to caculate the FC of the whole brain.The FC of different patients subgroups were compared with the paired HC groups and further compared the FC between patiens with EOD and LOD.Results:ANOVA analysis exhibited the FC alteration were widely located in bilateral frontal cortex,temporal lobe,basal ganglia,occipital cortex,paterial cortex and cerebellum.Relative to young HC,the FC was increased in left middle temporal gyrus,left cerebellum IX,left cerebellum Crusl,right middle frontal gyrus,right medial superior frontal gyrus,right insular,right anterior cingulate,right middle temporal gyrus,right angular,right precuneus and decreased in left middle frontal gyrus,left paracentral gyrus,right superior frontal gyrus,right inferior temporal gyrus,right supramarginal gyrus,right precentral gyrus,right postcentral gyrus,right superior occipital gyrus were observed in patients with EOD.In contrast,compare to old HC,the FC was increased in left obital middle frontal gyrus,left middle frontal gyrus,left inferior temporal gyrus,left putamen,left angular,left cerebellum Crusl,left cerebellum Crus2,right middle frontal gyrus,right angular,right pon and decreased in left middle frontal gyrus,right precentral gyrus,right paracentral gyrus,right fusiform,right parahippocampus,right inferior temporal gyrus,right middle occipital gyrus,right posterior cingulate,right calcarine were seen in patients with LOD.Compared to LOD,the FC decreased in left cerebellum Crus2,left cerebellum?_?,left calcarine and incresed FC in right orbital inferior frontal gyrus,right orbital middle frontal gyrus,right superior frontal gyrus and right middle frontal gyrus were boserved in EOD group.Conclusion:The FC alterations within DMN of the right hemisphere might associated with the pathomechanism of EOD group,but the increased FC within the anterior of DMN and decreased FC in the posterior of the DMN might associated with the pathomechanism of LOD patients.The FC of PCu and the whole brain were also different between EOD and LOD patients,implicated the depressed adult patients with different age-onset might have different pathogenesis of depression.