Dataset Information

Connectivity of the Cognitive Control Network During Response Inhibition as a Predictive and Response Biomarker in Major Depression: Evidence From a Randomized Clinical Trial.

ABSTRACT:

Background

In treating major depressive disorder, we lack tests anchored in neurobiology that predict antidepressant efficacy. Cognitive impairments are a particularly disabling feature of major depressive disorder. We tested whether functional connectivity during a response-inhibition task can predict response to antidepressants and whether its changes over time are correlated to symptom changes.

Methods

We analyzed data from outpatients with major depressive disorder (n = 124) randomized to receive escitalopram, sertraline, or venlafaxine (8 weeks) and healthy control subjects (n = 59; age 18-65 years). Before and after treatment, participants were interviewed and scanned using functional magnetic resonance imaging, and functional connectivity was measured using generalized psychophysiological interaction during response inhibition (Go-NoGo task). We investigated the interaction between treatment type and response (≥50% reduction on self-reported symptoms), coupling differences between responders and nonresponders at baseline, their correlation with symptom improvement, and their changes in time.

Results

During response inhibition, connectivity between the dorsolateral prefrontal cortex/supramarginal gyrus and supramarginal gyrus/middle temporal gyrus was associated with response to sertraline and venlafaxine, but not escitalopram. Sertraline responders had higher functional connectivity between these regions compared with nonresponders, whereas venlafaxine responders had lower functional connectivity. For sertraline, attenuation of connectivity in the precentral and superior temporal gyri correlated with posttreatment symptom improvement. For venlafaxine, enhancement of connectivity between the orbitofrontal cortex and subcortical regions correlated with symptom improvement.

Conclusions

Connectivity of the cognitive control circuit during response inhibition selectively and differentially predicts antidepressant treatment response and correlates with symptom improvement. These quantitative markers tied to the neurobiology of cognitive features of depression could be used translationally to predict and evaluate treatment response.

SUBMITTER: Tozzi L

PROVIDER: S-EPMC8628639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMajor depressive disorder (MDD) is characterized by core functional deficits in cognitive inhibition, which is crucial for emotion regulation. To assess the response to ruminative and negative mood states, it was hypothesized that MDD patients have prolonged disparities in the oscillatory dynamics of the frontal cortical regions across the life course of the disease.MethodA "go/no-go" response inhibition paradigm was tested in 31 MDD patients and 19 age-matched healthy controls after magnetoencephalography (MEG) scanning. The use of minimum norm estimates (MNE) examined the changes of inhibitory control network which included the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and left primary motor cortex (lM1). The power spectrum (PS) within each node and the functional connectivity (FC) between nodes were compared between two groups. Furthermore, Pearson correlation was calculated to estimate the relationship between altered FC and clinical features.ResultPS was significantly reduced in left motor and preSMA of MDD patients in both beta (13-30 Hz) and low gamma (30-50 Hz) bands. Compared to the HC group, the MDD group demonstrated higher connectivity between lM1 and preSMA in the beta band (t = 3.214, p = 0.002, FDR corrected) and showed reduced connectivity between preSMA and rIFG in the low gamma band (t = -2.612, p = 0.012, FDR corrected). The FC between lM1 and preSMA in the beta band was positively correlated with illness duration (r = 0.475, p = 0.005, FDR corrected), while the FC between preSMA and rIFG in the low gamma band was negatively correlated with illness duration (r = -0.509, p = 0.002, FDR corrected) and retardation factor scores (r = -0.288, p = 0.022, uncorrected).ConclusionIn this study, a clinical neurophysiological signature of cognitive inhibition leading to sustained negative affect as well as functional non-recovery in MDD patients is highlighted. Duration of illness (DI) plays a key role in negative emotional processing, heighten rumination, impulsivity, and disinhibition.

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