scholarly journals Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Naho Ichikawa ◽  
Giuseppe Lisi ◽  
Noriaki Yahata ◽  
Go Okada ◽  
Masahiro Takamura ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Learning Algorithm ◽  
Inferior Frontal Gyrus ◽  
Resting State Fmri ◽  
Posterior Cingulate Cortex ◽  
Brain Network ◽  
Major Depressive ◽  
Functional Connections ◽  
Limited Efficacy

Abstract The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second ‘most important’ FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future.

scholarly journals Microstructural deficits in the thalamus of major depressive disorder

2021 ◽  
Author(s):  
Pengfei Xu ◽  
Gangqiang Hou ◽  
Yuxuan Zhang ◽  
Yingli Zhang ◽  
Hui Ai ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Large Scale ◽  
Gray Matter Volume ◽  
Structural Connectivity ◽  
Brain Network ◽  
Microstructural Properties ◽  
Major Depressive ◽  
T1 Relaxation ◽  
Structural Abnormalities

Macroscopic structural abnormalities in the thalamus and thalamic circuits have been shown to contribute to the neuropathology of major depressive disorder (MDD). However, cytoarchitectonic properties underlying these macroscopic abnormalities remain unknown. The purpose of this study was to identify systematic deficits of brain architecture in depression, from structural brain network organization to microstructural properties. A multi-modal neuroimaging approach including diffusion, anatomical and quantitative magnetic resonance imaging (MRI) was used to examine structural-related alternations in 56 MDD patients compared with 35 age- and sex-matched controls. Structural networks were constructed and analyzed using seed-based probabilistic tractography. Morphometric measurements, including cortical thickness and voxel-based morphometry (VBM), were evaluated across the whole brain. A conjunction analysis was then conducted to identify key regions showing common structural alternations across modalities. The microstructural properties, macromolecular tissue volume (MTV) and T1 relaxation times of identified key regions were then calculated. Results showed multiple alterations of structural connectivity within a set of subcortical areas and their connections to cortical regions in MDD patients. These subcortical regions included the putamen, thalamus and caudate, which are predominately involved in the limbic-cortical-striatal-pallidal-thalamic network (LCSPT). Structural connectivity was disrupted within and between large-scale networks, mainly including subcortical networks, default mode networks and salience/ventral attention networks. Consistently, these regions also exhibited widespread volume reductions in MDD patients, specifically the bilateral thalamus, left putamen and right caudate. Importantly, the microstructural properties, T1 relaxation time of left thalamus were increased and negatively correlated with its gray matter volume in MDD patients. The present work to date sheds light on the neuropathological disruptions of LCSPT circuit in MDD, providing the first multi-modal neuroimaging evidence for the macro-micro structural abnormalities of the thalamus in patients with MDD. These findings have implications in understanding the abnormal changes of brain structures across development of MDD.

Altered Brain Network Degree Centrality in Major Depressive Disorder via Electro-Acupuncture Stimulation at Baihui(gv20)

2021 ◽  
Author(s):  
Shasha Li ◽  
Ya Chen ◽  
Gaoxiong Duan ◽  
Yong Pang ◽  
Huimei Liu ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Brain Function ◽  
Brain Regions ◽  
Brain Network ◽  
Degree Centrality ◽  
Major Depressive ◽  
Acupuncture Stimulation ◽  
Therapeutic Mechanisms ◽  
Abnormal Brain

Abstract Background: Although the acupuncture treatment of major depressive disorder(MDD) has been recognized by the latest clinical practice guidelines of the American Academy of Internal Medicine, complex therapeutic mechanisms need further to clarify. The aim of the study is investigate whether the aberrant resting state brain network in MDD patients could be regulated by acupuncture at GV20 using functional magnetic resonance imaging(fMRI) combined with degree centrality(DC) method. Results: Compared to healthy subjects, MDD patients exhibited significantly aberrant DC in widely brain regions, including cortical(PFC, precuneus, temporal, insula) and sub-cortical (thalamus, putamen and caudate) structures. Furthermore, results showed that acupuncture at GV20 induced down-regulation the DC of abnormal brain regions in MDD patients. Conclusions: Our findings provide imaging evidence to support that GV20-related acupuncture stimulation may modulate the abnormal brain function state in MDD patients by using fMRI technique combined with DC analysis. This study may partly interpret the neural mechanisms of acupuncture at GV20 which is used to treat patients with MDD in clinical. Trial registration: ChiCTR, ChiCTR-IOR-15006357. Registered 05 May 2015, http://www.chictr.org.cn/showproj.aspx?proj=10922.

scholarly journals Meta-analysis of cortical thickness abnormalities in medication-free patients with major depressive disorder

2019 ◽  
Vol 45 (4) ◽  
pp. 703-712 ◽  
Author(s):  
Qian Li ◽  
Youjin Zhao ◽  
Ziqi Chen ◽  
Jingyi Long ◽  
Jing Dai ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cortical Thickness ◽  
Meta Analysis ◽  
Temporal Cortex ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Anterior Cingulate ◽  
Middle Temporal Gyrus ◽  
Major Depressive

Abstract Alterations in cortical thickness have been identified in major depressive disorder (MDD), but findings have been variable and inconsistent. To date, no reliable tools have been available for the meta-analysis of surface-based morphometric (SBM) studies to effectively characterize what has been learned in previous studies, and drug treatments may have differentially impacted findings. We conducted a comprehensive meta-analysis of magnetic resonance imaging (MRI) studies that explored cortical thickness in medication-free patients with MDD, using a newly developed meta-analytic mask compatible with seed-based d mapping (SDM) meta-analytic software. We performed the meta-regression to explore the effects of demographics and clinical characteristics on variation in cortical thickness in MDD. Fifteen studies describing 529 patients and 586 healthy controls (HCs) were included. Medication-free patients with MDD, relative to HCs, showed a complex pattern of increased cortical thickness in some areas (posterior cingulate cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) and decreased cortical thickness in others (gyrus rectus, orbital segment of the superior frontal gyrus, and middle temporal gyrus). Most findings in the whole sample analysis were confirmed in a meta-analysis of studies recruiting medication-naive patients. Using the new mask specifically developed for SBM studies, this SDM meta-analysis provides evidence for regional cortical thickness alterations in MDD, mainly involving increased cortical thickness in the default mode network and decreased cortical thickness in the orbitofrontal and temporal cortex.

scholarly journals Gender Differences in Brain Serotonin Synthesis in Individuals with Major Depressive Disorder: A A-[11C]MT Pet Imaging Study

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
B.N. Frey ◽  
I. Skelin ◽  
Y. Sakai ◽  
M. Nishikawa ◽  
M. Diksic
Keyword(s):  
Gender Differences ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Inferior Frontal Gyrus ◽  
Anterior Cingulate ◽  
Brain Morphology ◽  
Brain Serotonin ◽  
Serotonin Synthesis ◽  
Major Depressive ◽  
Men And Women

Objective:Women are at higher risk than men to develop major depressive disorder (MDD), but the mechanisms underlying the higher risk for MDD in women are unknown. There is a wealth of data showing gender differences in brain morphology and function. In addition, preclinical studies have demonstrated reciprocal relationships between ovarian hormones and serotonin neurotransmission. Thus, gender differences in brain serotonin neurotransmission are potential underlying mechanisms. In the present study, we compared normalized α-[11C]methyl-L-tryptophan brain trapping constant (α-[11C]MTrp K*; ml/g/min), an index of serotonin synthesis, between men and women with MDD.Method:α-[11C]MTrp K* was measured in 25 medication-free individuals with MDD (13 females and 12 males) using positron emission tomography. Comparisons of normalized α-[11C]MTrp K* values between men and women were conducted at the voxel level using Statistical Parametric Mapping 2 (SPM2) analysis.Results:Women with MDD displayed significantly higher (p< 0.005) normalized α-[11C]MTrp K* than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus and superior parietal lobule, and occipital lingual gyrus.Conclusions:This finding suggests that depressive women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation. Gender differences in brain serotonin synthesis may be associated with higher risk for MDD in women because extra levels of tissue 5-HT could create non-physiological connections influencing changes in mood.

scholarly journals Reduced Default Mode Network Functional Connectivity in Patients with Recurrent Major Depressive Disorder

2018 ◽  
Author(s):  
Chao-Gan Yan ◽  
Xiao Chen ◽  
Le Li ◽  
Francisco Xavier Castellanos ◽  
Tong-Jian Bai ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Resting State ◽  
Resting State Fmri ◽  
Research Groups ◽  
Major Depressive ◽  
Default Mode ◽  
Normal Controls

ABSTRACTMajor Depressive Disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. Finally, all resting-state fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.SIGNIFICANCE STATEMENTFunctional connectivity within the default mode network in major depressive disorder patients has been frequently reported abnormal but with contradicting directions in previous small sample size studies. In creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments.

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