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Altered effective connectivity of the extended face processing system in depression and its association with treatment response: findings from the YoDA-C randomized controlled trial

Published online by Cambridge University Press:  21 July 2021

Alec J. Jamieson Open the ORCID record for Alec J. Jamieson [Opens in a new window] ,
Ben J. Harrison Open the ORCID record for Ben J. Harrison [Opens in a new window]  and
Christopher G. Davey Open the ORCID record for Christopher G. Davey [Opens in a new window]
Alec J. Jamieson*
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia
Ben J. Harrison
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia
Christopher G. Davey*
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia Department of Psychiatry, The University of Melbourne, Australia
*
Author for correspondence: Alec J. Jamieson, E-mail: [email protected]; Christopher G. Davey, E-mail: [email protected]
Author for correspondence: Alec J. Jamieson, E-mail: [email protected]; Christopher G. Davey, E-mail: [email protected]
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Abstract

Background

Depression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate depression associated alterations to directional connectivity and assess the utility of these parameters as predictors of treatment response.

Methods

Ninety-two unmedicated adolescents and young adults (mean age 20.1; 56.5% female) with moderate-to-severe major depressive disorder and 88 healthy controls (mean age 19.8; 61.4% female) completed an implicit emotional face processing fMRI task. Patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or placebo. Using dynamic causal modelling, we examined functional relationships between six brain regions implicated in emotional face processing, comparing both patients and controls and treatment responders and non-responders.

Results

Depressed patients demonstrated reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. During fearful expression processing patients showed reduced inhibition from the vmPFC to amygdala and reduced excitation from the amygdala to dlPFC. Response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing.

Conclusions

Our study clarifies the nature of face processing network alterations in adolescents and young adults with depression, highlighting key interactions between the amygdala and prefrontal cortex. Moreover, these findings highlight the potential utility of these interactions in predicting treatment response.

Keywords

Depressiontreatment responsedynamic causal modellingeffective connectivityemotion processingfMRI
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 16 , December 2021 , pp. 2933 - 2944
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

The online version of this article has been updated since original publication. A notice detailing the changes has also been published at https://doi.org/10.1017/S0033291721003342

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