Rostral anterior cingulate network effective connectivity in depressed adolescents and associations with treatment response in a randomized controlled trial

Jamieson, Alec J.; Harrison, Ben J.; Razi, Adeel; Davey, Christopher G.

doi:10.1038/s41386-021-01214-z

Cited by 42Functional Brain Connectivity StudiesTreatment of Major DepressionNeural and Behavioral Psychology Studies

Rostral anterior cingulate network effective connectivity in depressed adolescents and associations with treatment response in a randomized controlled trial

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Jamieson, Alec J., Harrison, Ben J., Razi, Adeel, Davey, Christopher G.·2022·Neuropsychopharmacology

DOI 10.1038/s41386-021-01214-zPMC PMC9018815

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Abstract

The rostral anterior cingulate cortex (rACC) is consistently implicated in the neurobiology of depression. While the functional connectivity of the rACC has been previously associated with treatment response, there is a paucity of work investigating the specific directional interactions underpinning these associations. We compared the fMRI resting-state effective connectivity of 94 young people with major depressive disorder and 91 healthy controls. Following the fMRI scan, patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or a placebo. Using spectral dynamic causal modelling, we examined the effective connectivity of the rACC with eight other regions implicated in depression: the left and right anterior insular cortex (AIC), amygdalae, and dorsolateral prefrontal cortex (dlPFC); and in the midline, the subgenual (sgACC) and dorsal anterior cingulate cortex (dACC). Parametric empirical Bayes was used to compare baseline differences between controls and patients and responders and non-responders to treatment. Depressed patients demonstrated greater inhibitory connectivity from the rACC to the dlPFC, AIC, dACC and left amygdala. Moreover, treatment responders illustrated greater inhibitory connectivity from the rACC to dACC, greater excitatory connectivity from the dACC to sgACC and reduced inhibitory connectivity from the sgACC to amygdalae at baseline. The inhibitory hyperconnectivity of the rACC in depressed patients aligns with hypotheses concerning the dominance of the default mode network over other intrinsic brain networks. Surprisingly, treatment responders did not demonstrate connectivity which was more similar to healthy controls, but rather distinct alterations that may have predicated their enhanced treatment response.

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Alterations in DMN connectivity are commonly observed post-mTBI and linked to cognitive complaints.
“Default Mode Network (DMN): Implicated in self-referential thought and introspection, alterations in DMN connectivity (often increased intra-network connectivity or altered connectivity with other networks) are commonly observed post-mTBI and linked to cognitive complaints 89 10 11 .”
From Functional MRI Guided Accelerated Intermittent Theta Burst Stimulation for Chronic Post-Concussive Syndrome: A Feasibility and Efficacy Study (2025) · cites this paper as [10]
The Introduction and ‘Differences in effective connectivity between depressed patients and controls’ discuss DMN connectivity in depression, not after mild traumatic brain injury. Searches for mTBI, concussion, and cognitive complaints found no passage addressing the claimed post-mTBI association. (LLM, conf=0.76)
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Authors: Jamieson, A. J., Harrison, B. J., Razi, A., & Davey, C. G.
Affiliations: The University of Melbourne (AU)
Canadian Institute for Advanced Research (CA)
Corresponding author: Jamieson, Alec J.
Davey, Christopher G.
ORCID: Jamieson, Alec J.
Harrison, Ben J.
Razi, Adeel
Davey, Christopher G.
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2021-11-15
Volume: 47
Issue: 6
Pages: 1240-1248
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/s41386-021-01214-z
PMC: PMC9018815
OpenAlex: W3211557128
Cited by: 41
References: 82
Citations by year: 2026: 7 · 2025: 15 · 2024: 13 · 2023: 3 · 2022: 3
FWCI: 2.50
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Australian Government Research Training Program Scholarship
Department of Health | National Health and Medical Research Council (1124472, 1061757)
Department of Education and Training | Australian Research Council (DE170100128, DP200100757)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: rostral anterior cingulate cortex, major depressive disorder, adolescents, effective connectivity, treatment response, cognitive behavioral therapy, fluoxetine, dynamic causal modeling, anterior insula, amygdala, dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, dorsal anterior cingulate cortex, default mode network
MeSH terms: Adolescent, Bayes Theorem, Brain, Depressive Disorder, Major, Major Depressive Disorder, Gyrus Cinguli, Humans, Magnetic Resonance Imaging

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Rostral anterior cingulate network effective connectivity in depressed adolescents and associations with treatment response in a randomized controlled trial

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