scholarly journals Multi-scale neural signatures of major depressive, anxiety, and stress-related disorders

2021 ◽  
Author(s):  
Peter Zhukovsky ◽  
Michael Wainberg ◽  
Milos Milic ◽  
Shreejoy Tripathy ◽  
Benoit Mulsant ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Fluid Intelligence ◽  
Neural Circuit ◽  
Distinct Pattern ◽  
Stress Disorders ◽  
Healthy Controls ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Circuit Function ◽  
Neural Signatures

Abstract The extent of shared and distinct neural mechanisms underlying major depressive disorder (MDD), anxiety and stress-related disorders is still unclear. We compared the neural signatures of these disorders in 5,405 UK Biobank patients and 21,727 healthy controls. We found the greatest case-control differences in resting-state functional connectivity and cortical thickness in MDD, followed by anxiety and stress-related disorders. Neural signatures for MDD and anxiety disorders were highly concordant, namely in altered frontostriatal connectivity, whereas stress-related disorders showed a distinct pattern. Controlling for cross-disorder genetic risk somewhat increased the similarity between functional neural signatures of stress-related disorders and both MDD and anxiety disorders. Among cases and healthy controls, reduced within-network and increased between-network frontoparietal and default mode connectivity was associated with poorer cognitive performance (processing speed, attention, associative learning and fluid intelligence). These results provide evidence for distinct neural circuit function impairments in MDD and anxiety disorders compared to stress disorders; yet cognitive impairment appears unrelated to diagnosis and varies with circuit function.

scholarly journals Abnormality of Resting-State Functional Connectivity in Major Depressive Disorder: A Study With Whole-Head Near-Infrared Spectroscopy

2021 ◽  
Vol 12 ◽  
Author(s):  
Eisuke Sakakibara ◽  
Yoshihiro Satomura ◽  
Jun Matsuoka ◽  
Shinsuke Koike ◽  
Naohiro Okada ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Infrared Spectroscopy ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Resting State ◽  
Near Infrared ◽  
Healthy Controls ◽  
Resting State Functional Connectivity ◽  
Major Depressive

Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that has advantages in clinical usage. Previous functional magnetic resonance imaging (fMRI) studies have found that the resting-state functional connectivity (RSFC) of the default mode network (DMN) is increased, while the RSFC of the cognitive control network (CCN) is reduced in patients with major depressive disorder (MDD) compared with healthy controls. This study tested whether the NIRS-based RSFC measurements can detect the abnormalities in RSFC that have been associated with MDD in previous fMRI studies. We measured 8 min of resting-state brain activity in 34 individuals with MDD and 78 age- and gender-matched healthy controls using a whole-head NIRS system. We applied a previously established partial correlation analysis for estimating RSFCs between the 17 cortical regions. We found that MDD patients had a lower RSFC between the left dorsolateral prefrontal cortex and the parietal lobe that comprise the CCN, and a higher RSFC between the right orbitofrontal cortex and ventrolateral prefrontal cortex, compared to those in healthy controls. The RSFC strength of the left CCN was negatively correlated with the severity of depressive symptoms and the dose of antipsychotic medication and positively correlated with the level of social functioning. The results of this study suggest that NIRS-based measurements of RSFCs have potential clinical applications.

scholarly journals Effects of escitalopram therapy on resting-state functional connectivity of subsystems of the default mode network in unmedicated patients with major depressive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian Cui ◽  
Yun Wang ◽  
Rui Liu ◽  
Xiongying Chen ◽  
Zhifang Zhang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Resting State ◽  
Fmri Data ◽  
Healthy Controls ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Default Mode

AbstractAntidepressants are often the first-line medications prescribed for patients with major depressive disorder (MDD). Given the critical role of the default mode network (DMN) in the physiopathology of MDD, the current study aimed to investigate the effects of antidepressants on the resting-state functional connectivity (rsFC) within and between the DMN subsystems. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 36 unmedicated MDD patients at baseline and after escitalopram treatment for 12 weeks. The rs-fMRI data were also collected from 61 matched healthy controls at the time point with the same interval. Then, we decomposed the DMN into three subsystems based on a template from previous studies and computed the rsFC within and between the three subsystems. Finally, repeated measures analysis of covariance was conducted to identify the main effect of group and time and their interaction effect. We found that the significantly reduced within-subsystem rsFC in the DMN core subsystem in patients with MDD at baseline was increased after escitalopram treatment and became comparable with that in the healthy controls, whereas the reduced within-subsystem rsFC persisted in the DMN dorsal medial prefrontal cortex (dMPFC) and medial temporal subsystems in patients with MDD following escitalopram treatment. In addition, the reduced between-subsystem rsFC between the core and dMPFC subsystem showed a similar trend of change after treatment in patients with MDD. Moreover, our main results were confirmed using the DMN regions from another brain atlas. In the current study, we found different effects of escitalopram on the rsFC of the DMN subsystems. These findings deepened our understanding of the neuronal basis of antidepressants’ effect on brain function in patients with MDD. The trial name: appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement. URL: http://www.chictr.org.cn/showproj.aspx?proj=21377. Registration number: ChiCTR-OOC-17012566.

scholarly journals Characterization of Potential Protein Biomarkers for Major Depressive Disorder Using Matrix-Assisted Laser Desorption Ionization/Time-of-Flight Mass Spectrometry

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4457
Author(s):  
Chieh-Hsin Lin ◽  
Hung Su ◽  
Chung-Chieh Hung ◽  
Hsien-Yuan Lane ◽  
Jentaie Shiea
Keyword(s):  
Mass Spectrometry ◽  
Time Of Flight ◽  
Laser Desorption ◽  
Healthy Controls ◽  
Laser Desorption Ionization ◽  
Major Depressive ◽  
Ionization Time ◽  
Maldi Tof ◽  
Matrix Assisted Laser ◽  
Matrix Assisted Laser Desorption

Matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry is a sensitive analytical tool for characterizing various biomolecules in biofluids. In this study, MALDI-TOF was used to characterize potential plasma biomarkers for distinguishing patients with major depressive disorder (MDD) from patients with schizophrenia and healthy controls. To avoid interference from albumin—the predominant protein in plasma—the plasma samples were pretreated using acid hydrolysis. The results obtained by MALDI-TOF were also validated by electrospray ionization-quadrupole time-of-flight (ESI-QTOF) mass spectrometry. The analytical results were further treated with principal component analysis (PCA), hierarchical clustering analysis (HCA), and receiver operating characteristic (ROC) curve analysis. The statistical analyses showed that MDD patients could be distinguished from schizophrenia patients and healthy controls by the lack of apolipoprotein C1 (Apo C1), which, in fact, was detected in healthy controls and schizophrenia patients. This protein is suggested to be a potential plasma biomarker for distinguishing MDD patients from healthy controls and schizophrenia patients. Since sample preparation for MALDI-TOF is very simple, high-throughput plasma apolipoprotein analysis for clinical purposes is feasible.

scholarly journals Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johanna Wallensten ◽  
Anna Nager ◽  
Marie Åsberg ◽  
Kristian Borg ◽  
Aniella Beser ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cd40 Ligand ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Sectional Study ◽  
Major Depressive ◽  
Cross Sectional ◽  
Ligand Expression ◽  
Minor Traumatic Brain Injury ◽  
Exhaustion Disorder

AbstractPatients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-derived EVs could be higher in patients with SED than in patients with major depressive disorder (MDD) and healthy controls. Patients with SED (n = 31), MDD (n = 31), and healthy matched controls (n = 61) were included. Astrocyte-derived EVs (previously known as microparticles) were measured in plasma with flow cytometry and labeled against glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). In addition, platelet EVs and their CD40 ligand expression were measured. Patients with SED had significantly higher concentrations of AQP4 and GFAP-positive EVs and EVs co-expressing AQP4/GFAP than patients with MDD and healthy controls. Patients with MDD had significantly higher concentrations of GFAP-positive EVs and EVs co-expressing AQP4/GFAP than healthy controls. Platelet EVs did not differ between groups. CD40 ligand expression was significantly higher in patients with SED and MDD than in controls. In conclusion, the present study suggests that patients with SED, and to some extent, patients with MDD, have increased leakage of astrocyte-derived EVs through the blood–brain barrier.

scholarly journals Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicolas Salvetat ◽  
Fabrice Chimienti ◽  
Christopher Cayzac ◽  
Benjamin Dubuc ◽  
Francisco Checa-Robles ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rna Editing ◽  
Whole Blood ◽  
Healthy Controls ◽  
Major Depressive ◽  
Suicide Attempters ◽  
Blood Samples ◽  
Depressed Patients ◽  
The Brain

AbstractMental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.

scholarly journals Neural circuit function redundancy in brain disorders

2021 ◽  
Vol 70 ◽  
pp. 74-80
Author(s):  
Beatriz E.P. Mizusaki ◽  
Cian O'Donnell
Keyword(s):  
Neural Circuit ◽  
Brain Disorders ◽  
Circuit Function
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