| Part 1The morphological changes of the subcortical grey matter in first episode,untreated major depressive disorderObjective:Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic(LCSPT)network or limbic-cortico-striatal-thalamic-cortical(LCSTC)circuits in patients with major depressive disorder(MDD),but few studies have investigated the subcortical structural abnormalities.Therefore,we sought to determine whether focal subcortical grey matter(GM)changes might be present in MDD at an early stage.Methods:We recruited 30 first episode,untreated patients with major depressive disorder(MDD)and 26 healthy control subjects.Voxel-based morphometry was used to evaluate cortical grey matter changes,and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures,respectively.In addition,probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM.Results:Compared to healthy controls,MDD patients had significant volume reductions in the bilateral putamen and left thalamus(Bonferroni-corrected,p<0.05).Meanwhile,the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen,and on the dorsal and ventral aspects of left thalamus in MDD patients(FWE-corrected,p<0.05).Additionally,a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity.Furthermore,probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen,thalamus and left nucleus accumbens,right amygdala have connections with the ipsilateral temporal lobe,and the area of shape deformation of the bilateral thalamus also have connections with the ipsilateral cerebellum.Besides,the left thalamus and nucleus accumbens have connections with orbitofrontal gyrus(OFG).All above-mentioned were found to be related to major depression.Conclusion:Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD,which support the role of subcortical structure in the pathophysiology of MDD.Meanwhile,the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.Part 2The morphological changes of the cortical and subcortical grey matter in first episode,untreated major depressive disorder with short-durationObjective:In order to further clarify the early pathological mechanism of depression,we selected the first episode,untreated MDD patients with short-duration to observe the structural changes of the cortical and subcortical gray matter.Methods:We recruited 26 first episode,short duration(<1 year),untreated patients with major depressive disorder(MDD)and 26 healthy control subjects.Voxel-based morphometry was used to evaluate cortical grey matter changes,and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures,respectively.In addition,probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM.Results:Compared to healthy controls,MDD patients with short duration had significant volume reductions in the left nucleus accumbens,putamen and thalamus(Bonferroni-corrected,p<0.05),and in the right amygdala(Bonferroni-corrected,p<0.05).Meanwhile,the vertex-based shape analysis showed regionally contracted areas on the ventromedial aspects of the bilateral putamen,and on the dorsal and ventral aspects of bilateral thalamus in MDD patients(FWE-corrected,p<0.05).Additionally,there was also shape change in the left nucleus accumbens and right amygdala(FWE,p<0.05).Besides,cortical thickness analysis showed local cortex thickness thinning in the left inferior temporal gyrus(ITG)and right precentral gyrus.But there was no correlation was found between local atrophy in the cortical and subcortical grey matter and clinical variables representing severity.Furthermore,probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes,which were found to be related to major depression.Conclusion:Our results suggested that structural abnormalities of the ITG,precentral gyrus,accumbens,amygdala,putamen and thalamus might be present in the first-episode MDD patients with short duration,which support the role of subcortical structure in the pathophysiology of MDD.Meanwhile,the present study showed that these cortical and subcortical structural abnormalities might be the potential trait markers of MDD.Part 3The brain structural network changes in first episode,untreated major depressive disorder with short-durationObjective:The present study uses the diffusion MRI to depict the unique WM structural network topology across the entire brain at the early stage of MDD.Methods:We recruited 21 first episode,short duration(<1 year),drug-naive depression patients and 25 healthy control subjects(HCs).To construct the WM structural network,we used atlas-based brain regions as nodes and the value of multiplying fiber number(FN)by the mean FA along the fiber bundles connected a pair of brain regions as edges.The structural network was respectively analyzed by graph theoretic and Network-Based Statistic(NBS)methods.Besides,Pearson partial correlation analysis was also performed to evaluated their association with the clinical variables.Results:Compared with healthy controls,short duration MDD patients had a significant decrease in the small-worldness(?).MDD patients group also had nodal efficiency reductions in the left orbitofrontal cortex(OFC)and thalamus.Meanwhile,the MDD patients group presented a significantly decreased subnetwork components,mainly located in the frontal-subcortical and limbic regions.Additionally,the structural connections between left thalamus and postcentral gyrus,as well as that in the left OFC,were negatively correlated with HDRS scores.Conclusion:Our results suggested that the abnormal structural network of the OFC and thalamus,involving the imbalance with the limbic system,might be a key pathology in early stage drug-naive depression patients. |
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