Frontoamygdalar effective connectivity in youth depression and treatment response.

Publication date: Jun 20, 2023

Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how they relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy (CBT) plus fluoxetine or placebo treatment. One hundred seven young people with moderate-to-severe depression and 94 healthy controls completed a functional magnetic resonance imaging cognitive reappraisal task. After the task, 87 participants with depression were randomized and received 12 weeks of CBT, plus either fluoxetine or placebo. Dynamic causal modelling was used to map frontoamygdalar effective connectivity during reappraisal and to assess the predictive capacity of baseline frontoamygdalar effective connectivity on depression diagnosis and post-treatment depression remission. Young people with depression showed weaker inhibitory modulation of vlPFC-to-amygdala connectivity during reappraisal (0. 29 Hz, posterior probability = 1. 00). Leave-one-out cross-validation demonstrated that this effect was sufficiently large to predict individual diagnostic status (r = .20, p = .003). Post-treatment depression remission was associated with weaker excitatory vmPFC-to-amygdala connectivity (-0. 56 Hz, posterior probability = 1. 00) during reappraisal at baseline, though this effect did not predict individual remission status (r = -. 02, p = .561). Frontoamygdalar effective connectivity shows promise in identifying youth depression diagnosis, and circuits responsible for negative affect regulation is implicated in responsiveness to first-line depression treatments.

Concepts Keywords
Amygdala Biological Markers
Fluoxetine Clinical Trial
Psychiatry Emotion Regulation
Randomized Major Depressive Disorder
Weeks Neurocircuitry


Type Source Name
disease MESH Major Depressive Disorder
drug DRUGBANK Fluoxetine

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