scholarly journals Reduced inhibition in depression impairs stimulus processing in human cortical microcircuits

2021 ◽  
Author(s):  
Heng Kang Yao ◽  
Alexandre Guet-McCreight ◽  
Frank Mazza ◽  
Homeira Moradi Chameh ◽  
Thomas D. Prevot ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Signal To Noise Ratio ◽  
Data Driven ◽  
Cortical Processing ◽  
Expression Data ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Baseline Activity ◽  
Cortical Microcircuits ◽  
The Impact

AbstractCortical processing depends on finely-tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered inhibition associated with treatment-resistant major depressive disorder (depression), which is implicated in cognitive deficits and rumination, but the link remains to be better established mechanistically in humans. Here, we tested the impact of reduced somatostatin interneuron inhibition on cortical processing in human neuronal microcircuits using a data-driven computational approach. We integrated human cellular, circuit and gene-expression data to generate detailed models of human cortical microcircuits in health and depression. We simulated microcircuit baseline and response activity and found reduced signal-to-noise ratio and increased false/failed detection of stimuli due to a higher baseline activity in depression. Our results thus applied novel models of human cortical microcircuits to demonstrate mechanistically how reduced inhibition impairs cortical processing in depression, providing quantitative links between altered inhibition and cognitive deficits.

scholarly journals Social cognition and major depressive disorder: impact on psychosocial function and therapeutic opportunities

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S300-S300
Author(s):  
Michael Weightman ◽  
Bernhard Baune
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cognitive Deficits ◽  
Psychosocial Functioning ◽  
Social Cognitive ◽  
Major Depressive ◽  
Depressed Patients ◽  
The Social ◽  
Social Cognitive Deficits ◽  
The Impact

AimsThis poster aims to examine the impact of social cognitive deficits on psychosocial functioning in depressed patients, as well as summarise the utility of various evidence-based therapeutic interventions employed to target these deficits. The stated hypotheses were twofold: (1) that social cognitive impairment in major depressive disorder will correlate with poorer psychosocial functioning; and (2) that these deficits will respond to existing anti-depressant therapies.BackgroundSocial cognition is an important adaptive trait that incorporates the identification, perception and interpretation of socially relevant information from the external world. It is frequently affected in major depressive disorder such that depressed patienMethodA review of the existing literature was performed in order to test the stated hypotheses. Pertinent sources were identified via the MEDLINE, EMBASE, PsycINFO, PubMed, Scopus and Google Scholar databases. A total of 107 studies met inclusion criteria for review.ResultImpaired social cognitive performance in depressed patients correlated with poorer psychosocial functioning across the key domains of general cognitive functioning and quality of life. Many current anti-depressant therapies were found to have a normalising effect on the social cognitive abilities of depressed subjects, both at a neural and functional level. Anti-depressant medications, in particular citalopram and reboxetine, appeared to correct facial affect recognition deficits, while a psychotherapeutic approach demonstrated improvements in theory of mind and negative interpretive bias. Data relating to other common treatments, such as electroconvulsive therapy, are limited.ConclusionThe impact and treatment of social cognitive deficits in major depressive disorder is an important emerging field. The social cognitive deficits evident in depressed patients are sometimes subtle, but afford a significant functional impact. Additionally, it appears these impairments are at least partially reversible using anti-depressants or psychotherapy.

scholarly journals Dissecting the impact of depression on decision-making

2019 ◽  
Vol 50 (10) ◽  
pp. 1613-1622 ◽  
Author(s):  
Victoria M. Lawlor ◽  
Christian A. Webb ◽  
Thomas V. Wiecki ◽  
Michael J. Frank ◽  
Madhukar Trivedi ◽  
...  
Keyword(s):  
Decision Making ◽  
Cognitive Deficits ◽  
Response Times ◽  
Major Depressive ◽  
Evidence Accumulation ◽  
Two Samples ◽  
Sensorimotor Deficit ◽  
The Impact ◽  
To Receive ◽  
Trial Participants

AbstractBackgroundCognitive deficits in depressed adults may reflect impaired decision-making. To investigate this possibility, we analyzed data from unmedicated adults with Major Depressive Disorder (MDD) and healthy controls as they performed a probabilistic reward task. The Hierarchical Drift Diffusion Model (HDDM) was used to quantify decision-making mechanisms recruited by the task, to determine if any such mechanism was disrupted by depression.MethodsData came from two samples (Study 1: 258 MDD, 36 controls; Study 2: 23 MDD, 25 controls). On each trial, participants indicated which of two similar stimuli was presented; correct identifications were rewarded. Quantile-probability plots and the HDDM quantified the impact of MDD on response times (RT), speed of evidence accumulation (drift rate), and the width of decision thresholds, among other parameters.ResultsRTs were more positively skewed in depressed v. healthy adults, and the HDDM revealed that drift rates were reduced—and decision thresholds were wider—in the MDD groups. This pattern suggests that depressed adults accumulated the evidence needed to make decisions more slowly than controls did.ConclusionsDepressed adults responded slower than controls in both studies, and poorer performance led the MDD group to receive fewer rewards than controls in Study 1. These results did not reflect a sensorimotor deficit but were instead due to sluggish evidence accumulation. Thus, slowed decision-making—not slowed perception or response execution—caused the performance deficit in MDD. If these results generalize to other tasks, they may help explain the broad cognitive deficits seen in depression.

scholarly journals Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder

2019 ◽  
Vol 130 (6) ◽  
pp. 923-935 ◽  
Author(s):  
Virginie Sterpenich ◽  
Sonia Vidal ◽  
Jeremy Hofmeister ◽  
Giorgio Michalopoulos ◽  
Victor Bancila ◽  
...  
Keyword(s):  
Neural Networks ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Ventral Tegmental Area ◽  
Emotional Processing ◽  
Judgment Task ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Ventral Tegmental ◽  
The Impact

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression. Methods Ten adult patients with a Montgomery–Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients’ performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration. Results A significant correlation (R2 = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area. Conclusions Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.

The impact of ‘cluster maintenance TMS’ on irritability occurring in major depressive disorder

2020 ◽  
pp. 103985622094303 ◽  
Author(s):  
Saxby Pridmore ◽  
Yvonne Turnier-Shea ◽  
Sheila Erger ◽  
Tamara May
Keyword(s):  
Major Depressive Disorder ◽  
Transcranial Magnetic Stimulation ◽  
Depressive Disorder ◽  
Magnetic Stimulation ◽  
Subjective Measure ◽  
Naturalistic Study ◽  
Treatment Resistant ◽  
Major Depressive ◽  
The Impact ◽  
Cluster Maintenance

Objective: To determine the impact of clustered maintenance transcranial magnetic stimulation (TMS) on irritability occurring in treatment-resistant major depressive disorder (MDD). Method: A naturalistic study of 106 courses that includes pre- and posttreatment assessments of subjective and objective depression and a subjective measure of irritability developed for this study. Results: Forty-six participants (35 females), mean age 43.2 years (14.3), completed 106 courses. There was a significant reduction in irritability and depression scores ( p < .001). The change in irritability scores was significantly correlated with the change in depression scores, r = .40, p < .001. Conclusion: TMS has the capacity to reduce the irritability co-occurring with treatment-resistant MDD, known to be responsive to TMS. This increases the possibility of using TMS in the treatment of irritability co-occurring with other disorders or standing alone (should irritability be categorized as a stand-alone disorder).

scholarly journals The Impact of BDNF Polymorphisms on Suicidality in Treatment-Resistant Major Depressive Disorder: A European Multicenter Study

2017 ◽  
Vol 20 (10) ◽  
pp. 782-787 ◽  
Author(s):  
Alexandra Schosser ◽  
Laura Carlberg ◽  
Raffaella Calati ◽  
Alessandro Serretti ◽  
Isabel Massat ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Multicenter Study ◽  
Treatment Resistant ◽  
Major Depressive ◽  
European Multicenter Study ◽  
The Impact
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