Molecular and Cellular Aspects of Major Depressive Disorder

2019 ◽  
pp. 62-89
Author(s):  
Revathy U. Chottekalapanda ◽  
Paul Greengard ◽  
Yotam Sagi
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Inflammatory Responses ◽  
The United States ◽  
Brain Regions ◽  
Major Depressive ◽  
Integrated Network ◽  
Diagnostic Aspects ◽  
Drug And Alcohol ◽  
Molecular Framework

Major depressive disorder (MDD) affects more than 20 million people in the United States. Depression is comorbid with other psychiatric disorders and can increase risks of drug and alcohol abuse and suicide. Available antidepressants have limited efficacy and new therapeutic targets are needed. MDD and antidepressant responses are mediated via neurotransmitter signaling mechanisms and inflammatory responses involving an integrated network of limbic brain regions that include hippocampus, prefrontal cortex, and nucleus accumbens. Although this limbic circuit is broadly described, researchers do not understand how the properties of neurons within the circuit are altered in depression. The authors present the regulation of the p11 signaling module in this circuit, describe the diagnostic aspects of p11 function, and lay out a cellular and molecular framework for the understanding of MDD and the development of novel antidepressant therapies.

scholarly journals Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiao Li ◽  
Jakob Seidlitz ◽  
John Suckling ◽  
Feiyang Fan ◽  
Gong-Jun Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Brain Regions ◽  
Cell Type ◽  
Major Depressive ◽  
Structural Differences ◽  
Neuroimaging Data ◽  
Cell Type Specific

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.

Use of a Second Generation Antipsychotic among Patients Diagnosed with Major Depressive Disorder in the United States

2012 ◽  
Vol 26 (4) ◽  
pp. 235-241
Author(s):  
David A. Sclar ◽  
Linda M. Robison ◽  
Lawrence J. Cohen ◽  
Kimberly K. Laubmeier ◽  
Iftekhar D. Kalsekar ◽  
...  
Keyword(s):  
United States ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Second Generation ◽  
The United States ◽  
Major Depressive ◽  
Second Generation Antipsychotic

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 Initial Evidence for Brain Plasticity Following a Digital Therapeutic Intervention for Depression

2019 ◽  
Vol 3 ◽  
pp. 247054701987788
Author(s):  
Megan M. Hoch ◽  
Gaelle E. Doucet ◽  
Dominik A. Moser ◽  
Won Hee Lee ◽  
Katherine A. Collins ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Resting State ◽  
Brain Plasticity ◽  
Memory Task ◽  
Brain Regions ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Emotional Faces ◽  
Task Training

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.

scholarly journals Association between cytomegalovirus infection, reduced gray matter volume, and resting-state functional hypoconnectivity in major depressive disorder: a replication and extension

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haixia Zheng ◽  
Bart N. Ford ◽  
Rayus Kuplicki ◽  
Kaiping Burrows ◽  
Peter W. Hunt ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Gray Matter ◽  
Resting State ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Affective Processing ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Matter Volume

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.

Major Depressive Disorder and Insulin Resistance in Nondiabetic Young Adults in the United States: The National Health and Nutrition Examination Survey, 1999-2002

2010 ◽  
Vol 13 (2) ◽  
pp. 175-181 ◽  
Author(s):  
Qiuhua Shen ◽  
Sandra Bergquist-Beringer ◽  
Valmi D. Sousa
Keyword(s):  
United States ◽  
Insulin Resistance ◽  
Young Adults ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
National Health ◽  
The United States ◽  
Nutrition Examination Survey ◽  
Major Depressive ◽  
Health And Nutrition

Objective: The association between depression and insulin resistance has been evaluated in previous studies with conflicting results. This study aimed to explore the relationship between major depressive disorder (MDD) and insulin resistance among nondiabetic young adult men and women in the United States. Method: Analyses of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 1999—2002, were conducted. The nationally representative sample consisted of 279 men and 358 women aged 20—39 years. MDD was determined by the WHO Composite International Diagnostic Interview (CIDI). Insulin resistance was measured by the homeostasis model assessment for insulin resistance. Results: Of 637 subjects, 16 men and 18 women had MDD (weighted percentage = 6.6%, SE = 1.2). Using logistic regression, no significant association was found between MDD and insulin resistance among the nondiabetic young adults in bivariate analysis (β = -0.01, OR = 0.99, 95% CI = [0.38, 2.57], p = .98). A significant interaction effect between gender and MDD was observed. For men, MDD was negatively associated with insulin resistance after adjusting for age, race/ethnicity, waist circumference, smoking status, systolic blood pressure and triglyceride level (β = -2.12, OR = 0.12, 95% CI = [0.02, 0.62], p = .01). No significant association between MDD and insulin resistance among women was found (β = 0.61, OR = 1.84, 95% CI = [0.47, 7.14], p = .38). Conclusions: Overall findings suggest there is no significant association between MDD and insulin resistance among nondiabetic young adults aged 20—39 years. However, gender differences in this relationship were noted.

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