Aberrant single-subject morphological brain networks in first-episode,treatment-naive adolescents with major depressive disorder

Background:Neuroimaging-based connectome studies have indicated that major depressive disorder(MDD)is associated with dis-rupted topological organization of large-scale brain networks.However,the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.Objective:To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.Methods:Twenty-five first-episode,treatment-naive adolescents with MDD and 19 healthy controls(HCs)underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests.Single-subject morphological brain networks were constructed separately based on cortical thickness,fractal dimension,gyrification index,and sulcus depth,and topologically characterized by graph-based approaches.Between-group differences were inferred by permutation testing.For significant alterations,partial correla-tions were used to examine their associations with clinical and neuropsychological variables in the patients.Finally,a support vector machine was used to classify the patients from controls.Results:Compared with the HCs,the patients exhibited topological alterations only in cortical thickness-based networks character-ized by higher nodal centralities in parietal(left primary sensory cortex)but lower nodal centralities in temporal(left parabelt complex,right perirhinal ectorhinal cortex,right area PHT and right ventral visual complex)regions.Moreover,decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients.These results were largely reproducible for binary and weighted network analyses.Finally,topological properties of the cortical thickness-based net-works were able to distinguish the MDD adolescents from HCs with 87.6%accuracy.Conclusion:Adolescent MDD is associated with disrupted topological organization of morphological brain networks,and the disrup-tions provide potential biomarkers for diagnosing and monitoring the disease.

Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy

Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.