The effects of antidepressant treatment on resting-state functional brain networks in patients with major depressive disorder
Open accessAbstract
Although most knowledge regarding antidepressant effects is at the receptor level, the neurophysiological correlates of these neurochemical changes remain poorly understood. Such an understanding could benefit from elucidation of antidepressant effects at the level of neural circuits, which would be crucial in identifying biomarkers for monitoring treatment efficacy of antidepressants. In this study, we recruited 20 first-episode drug-naive major depressive disorder (MDD) patients and performed resting-state functional magnetic resonance imaging (MRI) scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor-escitalopram. Twenty healthy controls (HCs) were also scanned twice with an 8-week interval. Whole-brain connectivity was analyzed using a graph-theory approach-functional connectivity strength (FCS). The analysis of covariance of FCS was used to determine treatment-related changes. We observed significant group-by-time interaction on FCS in the bilateral dorsomedial prefrontal cortex and bilateral hippocampi. Post hoc analyses revealed that the FCS values in the bilateral dorsomedial prefrontal cortex were significantly higher in the MDD patients compared to HCs at baseline and were significantly reduced after treatment; conversely, the FCS values in the bilateral hippocampi were significantly lower in the patients at baseline and were significantly increased after treatment. Importantly, FCS reduction in the dorsomedial prefrontal cortex was significantly correlated with symptomatic improvement. Together, these findings provided evidence that this commonly used antidepressant can selectively modulate the intrinsic network connectivity associated with the medial prefrontal-limbic system, thus significantly adding to our understanding of antidepressant effects at a circuit level and suggesting potential imaging-based biomarkers for treatment evaluation in MDD.
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Prefrontal cortex abnormalities observed either in MDD patients or in rodent models are partly corrected by antidepressants.
“PFC abnormalities observed either in MDD patients or in rodent models are partly corrected by antidepressants.”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Wang et al. 2015a
The Discussion reports that escitalopram reduced abnormally high connectivity strength in the dorsomedial prefrontal cortex of patients with MDD, supporting the patient portion of the claim. It does not report correction of prefrontal cortex abnormalities in rodent models; its discussion of animal studies concerns the hippocampus instead. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFCS alterations in these regions have been proven to be related to regulation of widespread cognitive, emotional, and executive control functions in MDD.
“The FCS alterations in these regions have been proven to be related to the regulation of widespread cognitive, emotional, and executive control functions in patients with MDD [6, 42-50].”
From Mapping neurophysiological subtypes of major depressive disorder using normative models of the functional connectome (2023) · cites this paper as [43]
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- Authors
- Wang, L., Xia, M., Li, K., Zeng, Y., Su, Y., Dai, W., Zhang, Q., Jin, Z., Mitchell, P. B., Yu, X., He, Y., & Si, T.
- Affiliations
- Peking University (CN)
- Beijing Normal University (CN)
- PLA 306 Hospital (CN)
- Peking University Sixth Hospital Beijing China
- Capital Medical University (CN)
- Black Dog Institute (AU)
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research Beijing Normal University Beijing China
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2014-10-21
- Volume
- 36
- Issue
- 2
- Pages
- 768-778
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6869500
- OpenAlex
- W2107693566
- Cited by
- 166
- References
- 61
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 16 · 2021: 17 · 2020: 17 · 2019: 15 · 2018: 19 · 2017: 24 · 2016: 18 · 2015: 8 · 2014: 1
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- National Natural Science Foundation of China (81225012, 81401479, 2014CB846102, 31221003, 81030028)
- Specialized Research Fund for the Doctoral Program of Higher Education of China
- National Science Fund for Distinguished Young Scholars (81225012)
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- major depressive disorder, antidepressant treatment, escitalopram, resting-state functional connectivity, dorsomedial prefrontal cortex, hippocampus, treatment response biomarkers, first-episode drug-naive depression, graph theory
- MeSH terms
- Adult, Brain, Brain Mapping, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Rest, Reproducibility of Results, Citalopram, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Antidepressive Agents, Second-Generation
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