Altered ACC subregional connectivity in depression and it's role in antidepressant effect
Poster No:
564
Submission Type:
Late-Breaking Abstract Submission
Authors:
Hanbing Shao1, Zilin Zhou1, Yingxue Gao1, Hailong Li1, Lianqing Zhang1, Xinyue Hu1, Weijie Bao1, Qiyong Gong1,2, Xiaoqi Huang1
Institutions:
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, 2Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, China
First Author:
Hanbing Shao
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Co-Author(s):
Zilin Zhou
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Yingxue Gao
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Hailong Li
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Lianqing Zhang
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Xinyue Hu
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Weijie Bao
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Qiyong Gong
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University|Department of Radiology, West China Xiamen Hospital of Sichuan University
Chengdu, China|Xiamen, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University|Department of Radiology, West China Xiamen Hospital of Sichuan University
Chengdu, China|Xiamen, China
Xiaoqi Huang
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, China
Introduction:
The anterior cingulate cortex (ACC) is crucial for emotional and cognitive function and can be subdivided into the caudal, dorsal, rostral, perigenual, and subgenual regions (Kelly et al., 2008; Margulies et al., 2007). ACC dysfunction has been highly implicated in major depressive disorder (MDD) (Peng et al., 2021; Zhou et al., 2024). However, the role of ACC subregions in MDD pathophysiology and antidepressant effect remains unclear. Our study assessed intrinsic ACC subregional connectivity in MDD versus healthy controls (HC) and conducted a longitudinal fMRI study to assess treatment-related neural changes in MDD subgroups stratified by treatment outcome.
Methods:
We enrolled 141 MDD patients and 138 age-, sex-, and education-matched HCs. All subjects were scanned using a 3T Siemens MRI. Of the MDD patients, 46 received antidepressants for 2-8 weeks and underwent resting-state fMRI at baseline and follow-up. Patients were classified into remission (rMDD, HAMD-17 ≤ 7) and non-remission (nrMDD) groups based on treatment response. Neuroimaging data were preprocessed using DPABI following a standardized pipeline. Based on previous studies of ACC subdivision, five bilateral seeds were defined in MNI space: caudal ACC (cACC, [±5, -10, 37]), dorsal ACC (dACC, [±5, 10, 33]), rostral ACC (rACC, [±5, 27, 21]), perigenual ACC (pgACC, [±5, 47, 11]), and subgenual ACC (sgACC, [±5, 34, -4]) (Fig.1a). The resting-state functional connectivity (rsFC) map of each ACC subregion were generated for all subjects. We utilized a voxel-based comparison to identify significant group differences (MDD vs HC). The significance threshold was set as P < 0.005 at the voxel level and P < 0.05 at the cluster level corrected for familywise error.
For longitudinal analysis, rsFC strengths between ACC subregions and group-different regions were extracted at baseline and follow-up for both rMDD and nrMDD groups. Paired t-tests were then used to assess treatment-related rsFC changes. Moreover, Spearman correlation was performed to examine relationships between rsFC alterations and symptom severity in MDD patients.
For longitudinal analysis, rsFC strengths between ACC subregions and group-different regions were extracted at baseline and follow-up for both rMDD and nrMDD groups. Paired t-tests were then used to assess treatment-related rsFC changes. Moreover, Spearman correlation was performed to examine relationships between rsFC alterations and symptom severity in MDD patients.
Results:
Demographic and clinical information of all participants is shown in Table 1.
MDD patients showed significantly enhanced rsFC relative to HC (Table 2, Fig.1b). Specifically, we found increased rsFC between bilateral pgACC and right inferior parietal lobule (IPL) in MDD, with right pgACC-IPL rsFC positively correlating with psychotic anxiety (Fig.1c). There were also significantly elevated rsFCs between bilateral pgACC and ventrolateral/dorsolateral prefrontal cortex (vlPFC/dlPFC), and between bilateral sgACC and right dlPFC, all in the frontoparietal network (FPN). Morever, increased rsFCs were found in the default mode network (DMN), including dorsomedial PFC (dmPFC), middle temporal gyrus, and dACC. The dACC-dmPFC rsFC correlated positively with HAMD score, weight change, and cognitive disturbance(Fig.1c).
Longitudinal follow-up of rMDD and nrMDD patients post-treatment showed widespread rsFC reductions, particularly in rMDD. Notably, connectivity between left pgACC and both bilateral vlPFC and right dlPFC decreased significantly in rMDD patients and converged with HC levels(Fig.1b). The pgACC-vlPFC rsFC changes were positively correlated with reduction rates of HAMA score, somatic anxiety, and weight change(Fig.1d).
MDD patients showed significantly enhanced rsFC relative to HC (Table 2, Fig.1b). Specifically, we found increased rsFC between bilateral pgACC and right inferior parietal lobule (IPL) in MDD, with right pgACC-IPL rsFC positively correlating with psychotic anxiety (Fig.1c). There were also significantly elevated rsFCs between bilateral pgACC and ventrolateral/dorsolateral prefrontal cortex (vlPFC/dlPFC), and between bilateral sgACC and right dlPFC, all in the frontoparietal network (FPN). Morever, increased rsFCs were found in the default mode network (DMN), including dorsomedial PFC (dmPFC), middle temporal gyrus, and dACC. The dACC-dmPFC rsFC correlated positively with HAMD score, weight change, and cognitive disturbance(Fig.1c).
Longitudinal follow-up of rMDD and nrMDD patients post-treatment showed widespread rsFC reductions, particularly in rMDD. Notably, connectivity between left pgACC and both bilateral vlPFC and right dlPFC decreased significantly in rMDD patients and converged with HC levels(Fig.1b). The pgACC-vlPFC rsFC changes were positively correlated with reduction rates of HAMA score, somatic anxiety, and weight change(Fig.1d).
Conclusions:
Our results showed specific functional alterations in distinct ACC subregions in MDD, with increased rsFC in FPN and DMN linked to depressive and anxiety symptoms. Longitudinal data showed antidepressants significantly altered rsFC abnormalities, with more pronounced improvements observed in rMDD patients. Notably, treatment-related changes in pgACC-vlPFC rsFC held significant relevance to anxiety relief. These findings provide new insights into the pathophysiological role of ACC subregions and their interactions with FPN and DMN in MDD, and suggest pgACC-vlPFC connectivity may serve as a potential predictive biomarker for antidepressant treatment.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Keywords:
FUNCTIONAL MRI
Other - Major depressive disorder (MDD); Anterior cingulate cortex (ACC); Subregions; Resting-state functional connectivity (rsFC); Antidepressant effect
1|2Indicates the priority used for review
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Provide references using APA citation style.
Margulies, D. S., Kelly, A. M., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2007). Mapping the functional connectivity of anterior cingulate cortex. NeuroImage, 37(2), 579–588.
Peng, X., Wu, X., Gong, R., Yang, R., Wang, X., Zhu, W., & Lin, P. (2021). Sub-regional anterior cingulate cortex functional connectivity revealed default network subsystem dysfunction in patients with major depressive disorder. Psychological medicine, 51(10), 1687–1695.
Zhou, Z., Gao, Y., Bao, W., Liang, K., Cao, L., Tang, M., Li, H., Hu, X., Zhang, L., Sun, H., Roberts, N., Gong, Q., & Huang, X. (2024). Distinctive intrinsic functional connectivity alterations of anterior cingulate cortex subdivisions in major depressive disorder: A systematic review and meta-analysis. Neuroscience and biobehavioral reviews, 159, 105583.