Major Depressive Disorder in Neuroimaging: What is Beyond Fronto-limbic Model?

2019 ◽  
Vol 15 (1) ◽  
pp. 37-43
Author(s):  
Chien-Han Lai

Background: The major depressive disorder (MDD) is a chronic illness with major manifestations in cognitive, social and occupational functions. The pathophysiological model is an intrigue issue for scientists to understand the origin of MDD. Objective: In the beginning, the cortico-limbic-striato-pallidal-thalamic model has been proposed to link the clinical symptoms with the abnormalities in brain structure and function. However, the model is still evolving due to recent advances in the neuroimaging techniques, especially for functional magnetic resonance imaging (fMRI). The recent findings in the fMRI studies in MDD showed the importance of fronto-limbic model for the modulations between cognitive function and primitive and negative emotions. Method: This review will focus on the literature of fMRI studies in MDD with findings not in the fronto-limbic structures. Results: Additional regions beyond the fronto-limbic model have been observed in some literature of MDD. Some regions in the parietal, temporal and occipital lobes have been shown with the alterations in gray matter, white matter and brain function. The importance of sensory detection, visuospatial function, language reception, motor response and emotional memories in these regions might provide the clues to understand the cognitive misinterpretations related to altered reception of outside information, behavioral responses related to biased cognition and emotional memories and clinical symptoms related to the significant alterations of interactions between different brain regions. Conclusion: Future studies to establish a more comprehensive model for MDD will be warranted, especially for the model beyond the fronto-limbic structures.

Author(s):  
Deanna M. Barch ◽  
David Pagliaccio

This chapter reviews associations between early life stress and brain structure and function as assessed by structural and functional magnetic resonance imaging. Particularly, this chapter focuses on structural associations in children and adults and the regional overlap with neural alterations observed in major depressive disorder, though we also more briefly cover diffusion imaging, task-based imaging, and resting-state functional connectivity. Major depressive disorder is highlighted given that early life stress is a critical risk factor for depression and the neural alterations observed with stress and depression may serve as key mediating factors of this association. A brief methodological overview is provided for each neuroimaging domain as well as a discussion of limitations and future directions for this field.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Wei Wang ◽  
Lijun Kang ◽  
Nan Zhang ◽  
Xin Guo ◽  
Peilin Wang ◽  
...  

Suicidal ideation (SI) is a direct risk factor for suicide in patients with depression. Regarding the emergence of SI, previous studies have discovered many risk factors, including childhood abuse as the major public problem. Previous imaging studies have demonstrated that SI or childhood abuse has effects on brain structure and function, respectively, but the interaction effects between them have not been fully studied. To explore the interaction effect between SI and childhood abuse, 215 patients with major depressive disorder completed the Childhood Trauma Questionnaire to evaluate childhood abuse and Beck’s Scale for Suicidal Ideation to evaluate SI. Then, they completed magnetic resonance imaging (MRI) within one week after completing questionnaires. Respectively, we preprocessed the structural and functional images and analyzed gray matter volumes (GMV) and mean fractional amplitude of low-frequency fluctuation (mfALFF) values. Results showed that the changes of GMV in the cuneus, precuneus, paracentric lobule, inferior frontal gyrus, and caudate nucleus and local activity in cuneal and middle temporal gyrus are in relation with SI and childhood abuse. And in left caudate, SI and childhood abuse interact with each other on the influence of GMV. That is, the influence of SI in GMV was related to childhood abuse, and the influence of childhood abuse in GMV was also related to SI. Therefore, the combination of SI and childhood abuse based on imaging should help us better understand the suicide ideation developing mechanism and propose more effective targeted prevention strategies for suicide prevention.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiao Li ◽  
Jakob Seidlitz ◽  
John Suckling ◽  
Feiyang Fan ◽  
Gong-Jun Ji ◽  
...  

AbstractMajor depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.


2021 ◽  
Author(s):  
Shasha Li ◽  
Ya Chen ◽  
Gaoxiong Duan ◽  
Yong Pang ◽  
Huimei Liu ◽  
...  

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.


2019 ◽  
Vol 50 (3) ◽  
pp. 384-395 ◽  
Author(s):  
Yamin Zhang ◽  
Mingli Li ◽  
Qiang Wang ◽  
Jacob Shujui Hsu ◽  
Wei Deng ◽  
...  

AbstractBackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide and influenced by both environmental and genetic factors. Genetic studies of MDD have focused on common variants and have been constrained by the heterogeneity of clinical symptoms.MethodsWe sequenced the exome of 77 cases and 245 controls of Han Chinese ancestry and scanned their brain. Burden tests of rare variants were performed first to explore the association between genes/pathways and MDD. Secondly, parallel Independent Component Analysis was conducted to investigate genetic underpinnings of gray matter volume (GMV) changes of MDD.ResultsTwo genes (CSMD1, p = 5.32×10−6; CNTNAP5, p = 1.32×10−6) and one pathway (Neuroactive Ligand Receptor Interactive, p = 1.29×10−5) achieved significance in burden test. In addition, we identified one pair of imaging-genetic components of significant correlation (r = 0.38, p = 9.92×10−6). The imaging component reflected decreased GMV in cases and correlated with intelligence quotient (IQ). IQ mediated the effects of GMV on MDD. The genetic component enriched in two gene sets, namely Singling by G-protein coupled receptors [false discovery rate (FDR) q = 3.23×10−4) and Alzheimer Disease Up (FDR q = 6.12×10−4).ConclusionsBoth rare variants analysis and imaging–genetic analysis found evidence corresponding with the neuroinflammation and synaptic plasticity hypotheses of MDD. The mediation of IQ indicates that genetic component may act on MDD through GMV alteration and cognitive impairment.


2019 ◽  
Vol 3 ◽  
pp. 247054701987788
Author(s):  
Megan M. Hoch ◽  
Gaelle E. Doucet ◽  
Dominik A. Moser ◽  
Won Hee Lee ◽  
Katherine A. Collins ◽  
...  

Background Digital therapeutics such as cognitive–emotional training have begun to show promise for the treatment of major depressive disorder. Available clinical trial data suggest that monotherapy with cognitive–emotional training using the Emotional Faces Memory Task is beneficial in reducing depressive symptoms in patients with major depressive disorder. The aim of this study was to investigate whether Emotional Faces Memory Task training for major depressive disorder is associated with changes in brain connectivity and whether changes in connectivity parameters are related to symptomatic improvement. Methods Fourteen major depressive disorder patients received Emotional Faces Memory Task training as monotherapy over a six-week period. Patients were scanned at baseline and posttreatment to identify changes in resting-state functional connectivity and effective connectivity during emotional working memory processing. Results Compared to baseline, patients showed posttreatment reduced connectivity within resting-state networks involved in self-referential and salience processing and greater integration across the functional connectome at rest. Moreover, we observed a posttreatment increase in the Emotional Faces Memory Task-induced modulation of connectivity between cortical control and limbic brain regions, which was associated with clinical improvement. Discussion These findings provide initial evidence that cognitive–emotional training may be associated with changes in short-term plasticity of brain networks implicated in major depressive disorder. Conclusion Our findings pave the way for the principled design of large clinical and neuroimaging studies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haixia Zheng ◽  
Bart N. Ford ◽  
Rayus Kuplicki ◽  
Kaiping Burrows ◽  
Peter W. Hunt ◽  
...  

AbstractHuman cytomegalovirus (HCMV) is a neurotropic herpes virus known to cause neuropathology in patients with impaired immunity. Previously, we reported a reduction in the gray matter volume (GMV) of several brain regions in two independent samples of participants who were seropositive for HCMV (HCMV+) compared to matched participants who were seronegative for HCMV (HCMV−). In addition to an independent replication of the GMV findings, this study aimed to examine whether HCMV+ was associated with differences in resting-state functional connectivity (rsfMRI-FC). After balancing on 11 clinical/demographic variables using inverse probability of treatment weighting (IPTW), GMV and rsfMRI-FC were obtained from 99 participants with major depressive disorder (MDD) who were classified into 42 HCMV+ and 57 HCMV− individuals. Relative to the HCMV− group, the HCMV+ group showed a significant reduction of GMV in nine cortical regions. Volume reduction in the right lateral orbitofrontal cortex (standardized beta coefficient (SBC) = −0.32, [95%CI, −0.62 to −0.02]) and the left pars orbitalis (SBC = −0.34, [95%CI, −0.63 to −0.05]) in the HCMV+ group was also observed in the previous study. Regardless of the parcellation method or analytical approach, relative to the HCMV− group, the HCMV+ group showed hypoconnectivity between the hubs of the sensorimotor network (bilateral postcentral gyrus) and the hubs of the salience network (bilateral insula) with effect sizes ranging from SBC = −0.57 to −0.99. These findings support the hypothesis that a positive HCMV serostatus is associated with altered connectivity of regions that are important for stress and affective processing and further supports a possible etiological role of HCMV in depression.


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