Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder
Open accessAbstract
Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological agents for treating obsessive-compulsive disorder (OCD). However, because nearly half of patients show insufficient SSRI responses, serotonergic dysfunction in heterogeneous OCD patients should be investigated for precision medicine. We aimed to determine whether functional connectivity (FC) of the raphe nucleus (RN), the major source of most serotonergic neurons, was altered in OCD patients and could predict the SSRI response. A total of 102 medication-free OCD patients and 101 matched healthy control (HC) subjects participated in resting-state functional magnetic resonance imaging. Among them, 54 OCD patients were treated with SSRIs for 16 weeks, resulting in 26 responders and 28 nonresponders. Seed-based whole brain FC with the RN as a seed region was compared between the OCD and HC groups, as well as between SSRI responders and nonresponders. FC cluster values showing significant group differences were used to investigate factors correlated with symptomatic severity before treatment and predictive of SSRI response. Compared to HCs, OCD patients exhibited significantly larger FC between the RN and temporal cortices including the middle temporal gyrus (MTG), paracingulate gyrus, amygdala, hippocampus, putamen, thalamus, and brain stem. Greater RN-left MTG FC was positively correlated with OC symptom severity at baseline. In addition, larger FC of the RN-left MTG was also found in SSRI nonresponders compared to responders, which was a significant predictor of SSRI response after 16 weeks. The FC of RN may reflect the neurobiological underpinning of OCD and could aid future precision medicine as a differential brain-based biomarker.
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In patients, the greater this connectivity, the poorer the therapeutic response to selective serotonin reuptake inhibitors (SSRIs).
“In patients, the greater this connectivity, the poorer the therapeutic response to selective serotonin reuptake inhibitors (SSRIs).”
From Error-Related Brain Potentials as Biomarkers of Pathology Severity and Treatment Resistance in Patients With Obsessive-Compulsive Disorder (2026) · cites this paper as [46]
Kim et al. showed that OCD patients exhibited greater functional connectivity than controls between the raphe nucleus and temporal cortices, particularly the middle temporal gyrus.
“Finally, Kim et al. [46] showed that OCD patients exhibited greater functional connectivity than controls between the raphe nucleus and temporal cortices, particularly the aforementioned middle temporal gyrus.”
From Error-Related Brain Potentials as Biomarkers of Pathology Severity and Treatment Resistance in Patients With Obsessive-Compulsive Disorder (2026) · cites this paper as [46]
Stronger functional connectivity between serotonergic raphe nuclei and temporal and limbic regions including the amygdala predicts better SSRI response in OCD.
“Further, stronger functional connectivity between the serotonergic raphe nuclei and temporal and limbic regions including the amygdala predicts better response to SSRIs in OCD [58].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [58]
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“The independent variables in both the binary logistic regression and the multiple regression analysis included the following: Altered FC of the RN in SSRI nonresponders compared to responders; demographic characteristics that showed differences between the two groups (i.e., age, IQ, years of education, DOI); and basel…”
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“Finally, Kim et al. [46] showed that OCD patients exhibited greater functional connectivity than controls between the raphe nucleus and temporal cortices, particularly the afore-mentioned middle temporal gyrus.”
Obsessive Compulsive Disorder: Neurobiology and Treatment
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- Authors
- Kim, M., Kwak, S., Yoon, Y. B., Kwak, Y. B., Kim, T., Cho, K. I. K., Lee, T. Y., & Kwon, J. S.
- Affiliations
- Seoul National University (KR)
- Washington University in St. Louis (US)
- Corresponding author
- Kwon, Jun Soo
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2019-06-12
- Volume
- 44
- Issue
- 12
- Pages
- 2073-2081
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6898154
- OpenAlex
- W2949255019
- Cited by
- 37
- References
- 56
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 1
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (2016R1E1A1A02921618)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- obsessive-compulsive disorder, raphe nuclei, functional connectivity, selective serotonin reuptake inhibitors, treatment response prediction, serotonergic dysfunction, middle temporal gyrus, symptom severity, precision medicine
- MeSH terms
- Adult, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Obsessive-Compulsive Disorder, Raphe Nuclei, Selective Serotonin Reuptake Inhibitors, Young Adult
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