Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks

Abstract Background Major depressive disorder (MDD) often presents alongside physical illnesses, such as a high incidence of subclinical hypothyroidism (SHypo) in patients, highlighting the common occurrence of these comorbidities. Recent research has indicated that the presence of comorbid SHypo in...

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Main Authors: Shuai Zhao, Jindan Wu, Xiaomei Liu, Yishan Du, Xiaoqin Wang, Yi Xia, Hao Sun, Haowen Zou, Xumiao Wang, Zhilu Chen, Rui Yan, Hao Tang, Qing Lu, Zhijian Yao
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Language:English
Published: BMC 2025-03-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-03995-2
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author Shuai Zhao
Jindan Wu
Xiaomei Liu
Yishan Du
Xiaoqin Wang
Yi Xia
Hao Sun
Haowen Zou
Xumiao Wang
Zhilu Chen
Rui Yan
Hao Tang
Qing Lu
Zhijian Yao
author_facet Shuai Zhao
Jindan Wu
Xiaomei Liu
Yishan Du
Xiaoqin Wang
Yi Xia
Hao Sun
Haowen Zou
Xumiao Wang
Zhilu Chen
Rui Yan
Hao Tang
Qing Lu
Zhijian Yao
author_sort Shuai Zhao
collection DOAJ
description Abstract Background Major depressive disorder (MDD) often presents alongside physical illnesses, such as a high incidence of subclinical hypothyroidism (SHypo) in patients, highlighting the common occurrence of these comorbidities. Recent research has indicated that the presence of comorbid SHypo in individuals diagnosed with MDD may result in notable alterations in both brain structure and function. This study aimed was to investigate the neurological mechanisms underlying this co-occurrence using a data-driven approach to analyze brain activity patterns. Methods Twenty-nine patients diagnosed with MDD without any comorbid conditions (nSHypo-MDD) were included in the study, along with 29 MDD patients who also had SHypo (SHypo-MDD), 26 patients with SHypo only, and 29 healthy individuals as controls (HCs). Each participant received resting-state functional magnetic resonance imaging scans and underwent neuropsychological evaluations. Results We found significantly altered functional connectivity (FC) within the resting-state networks (RSNs) of the ventral and dorsal sensorimotor network (VSMN and DSMN) and occipital pole visual network (PVN) (p < 0.05, FDR corrected). A vital interaction effect between SHypo and MDD was detected in the PVN, showing that SHypo-MDD patients had higher FC values in the left cuneus than nSHypo-MDD patients. Serum-free triiodothyronine (FT3) levels in SHypo-MDD patients demonstrated an inverse relationship with FC values of the right supplementary motor area (SMA.R) (r = − 0.563, p = 0.003). Furthermore, the FC values in the left cuneus are positively associated with the Digit Symbol Substitution Test (DSST) scores (r = 0.507, p = 0.008). Conclusions Our study reveals significant FC changes in SHypo-MDD patients, particularly in the PVN, VSMN, and DSMN, suggesting compensatory mechanisms that mitigate cognitive deficits and highlighting the need for integrated management of SHypo and MDD to improve cognitive outcomes.
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spelling doaj-art-ece36bbca8254c8d9b6d231be142598e2025-08-20T02:10:16ZengBMCBMC Medicine1741-70152025-03-0123111110.1186/s12916-025-03995-2Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networksShuai Zhao0Jindan Wu1Xiaomei Liu2Yishan Du3Xiaoqin Wang4Yi Xia5Hao Sun6Haowen Zou7Xumiao Wang8Zhilu Chen9Rui Yan10Hao Tang11Qing Lu12Zhijian Yao13Department of Psychiatry, The Affiliated Psychological Hospital of Anhui Medical UniversityDepartment of Endocrinology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Endocrinology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversitySchool of Biological Sciences & Medical Engineering, Southeast UniversityDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityAbstract Background Major depressive disorder (MDD) often presents alongside physical illnesses, such as a high incidence of subclinical hypothyroidism (SHypo) in patients, highlighting the common occurrence of these comorbidities. Recent research has indicated that the presence of comorbid SHypo in individuals diagnosed with MDD may result in notable alterations in both brain structure and function. This study aimed was to investigate the neurological mechanisms underlying this co-occurrence using a data-driven approach to analyze brain activity patterns. Methods Twenty-nine patients diagnosed with MDD without any comorbid conditions (nSHypo-MDD) were included in the study, along with 29 MDD patients who also had SHypo (SHypo-MDD), 26 patients with SHypo only, and 29 healthy individuals as controls (HCs). Each participant received resting-state functional magnetic resonance imaging scans and underwent neuropsychological evaluations. Results We found significantly altered functional connectivity (FC) within the resting-state networks (RSNs) of the ventral and dorsal sensorimotor network (VSMN and DSMN) and occipital pole visual network (PVN) (p < 0.05, FDR corrected). A vital interaction effect between SHypo and MDD was detected in the PVN, showing that SHypo-MDD patients had higher FC values in the left cuneus than nSHypo-MDD patients. Serum-free triiodothyronine (FT3) levels in SHypo-MDD patients demonstrated an inverse relationship with FC values of the right supplementary motor area (SMA.R) (r = − 0.563, p = 0.003). Furthermore, the FC values in the left cuneus are positively associated with the Digit Symbol Substitution Test (DSST) scores (r = 0.507, p = 0.008). Conclusions Our study reveals significant FC changes in SHypo-MDD patients, particularly in the PVN, VSMN, and DSMN, suggesting compensatory mechanisms that mitigate cognitive deficits and highlighting the need for integrated management of SHypo and MDD to improve cognitive outcomes.https://doi.org/10.1186/s12916-025-03995-2Brain NetworksSubclinical HypothyroidismMajor depressive disorder
spellingShingle Shuai Zhao
Jindan Wu
Xiaomei Liu
Yishan Du
Xiaoqin Wang
Yi Xia
Hao Sun
Haowen Zou
Xumiao Wang
Zhilu Chen
Rui Yan
Hao Tang
Qing Lu
Zhijian Yao
Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
BMC Medicine
Brain Networks
Subclinical Hypothyroidism
Major depressive disorder
title Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
title_full Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
title_fullStr Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
title_full_unstemmed Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
title_short Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
title_sort exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks
topic Brain Networks
Subclinical Hypothyroidism
Major depressive disorder
url https://doi.org/10.1186/s12916-025-03995-2
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