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Subcortical functional connectivity alterations in first-episode medication-naïve adolescents with major depressive disorder.

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Title: Subcortical functional connectivity alterations in first-episode medication-naïve adolescents with major depressive disorder.
Authors: Sun, Lei (AUTHOR), Zhou, Zilin (AUTHOR), Feng, Ruohan (AUTHOR), Gao, Yingxue (AUTHOR), Bao, Weijie (AUTHOR), He, Hong (AUTHOR), Li, Hongwei (AUTHOR), Hu, Xinyue (AUTHOR), Li, Hailong (AUTHOR), Zhang, Lianqing (AUTHOR), Huang, Guoping (AUTHOR), Huang, Xiaoqi (AUTHOR)
Source: European Child & Adolescent Psychiatry. Nov2025, Vol. 34 Issue 11, p3535-3547. 13p.
Subjects: Diagnosis of post-traumatic stress disorder, Sleep disorder diagnosis, Life change events, Statistical correlation, Functional connectivity, Amygdaloid body, Research funding, Questionnaires, Family relations, Descriptive statistics, Magnetic resonance imaging, Symptoms, Basal ganglia, Families, Cerebral cortex, Thalamus, Research, Comparative studies, Data analysis software, Psychological tests, Hippocampus (Brain), Mental depression, Psychosocial factors, Adolescence
Geographic Terms: China
Abstract: Major depressive disorder (MDD) demonstrates significant alterations in intrinsic functional connectivity (FC) of the subcortical networks (SCN). However, the neurobiological mechanisms underlying these changes in adolescents with MDD and their association with stressors and sleep disturbances remain poorly understood. Using seed-based functional connectivity analysis, we investigated changes in intrinsic connectivity of the SCN in 83 first-episode medication-naïve adolescents with MDD (aMDD) and 59 healthy controls (HC). We then examined the correlation between the SCN connectivity alterations with sleep disturbances and stress factors, measured by the Pittsburgh Sleep Quality Index (PSQI), the Adolescent Life Events Checklist (ASLEC), and the Family Environment Scale-Chinese Version (FES-CV). Compared with HC, aMDD patients showed decreased connectivity between multiple subcortical regions (amygdala, hippocampus, nucleus accumbens (NAc), and thalamus) and cortical regions of the limbic (orbital frontal cortex, inferior temporal gyrus, temporal pole), visual (middle occipital gyrus) and sensorimotor (precentral gyrus) networks. Moreover, we observed that reduced amygdala- and NAc-based FC was correlated with more stress from life events, while reduced thalamus-based FC was associated with more severe sleep disturbances. Our study was the first to comprehensively investigate the SCN-based FC alterations in adolescents with MDD. We revealed disruptions in connectivity between the SCN and cortical networks in aMDD, and further identified potential environmental mechanisms associated with these SCN-based dysconnectivity patterns. These findings underscore critical role of the SCN in the neurobiological mechanisms of aMDD and suggest potential targets for developing novel treatment strategies for adolescents with MDD. [ABSTRACT FROM AUTHOR]
Copyright of European Child & Adolescent Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Subcortical functional connectivity alterations in first-episode medication-naïve adolescents with major depressive disorder.
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  Data: <searchLink fieldCode="AR" term="%22Sun%2C+Lei%22">Sun, Lei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou%2C+Zilin%22">Zhou, Zilin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Feng%2C+Ruohan%22">Feng, Ruohan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gao%2C+Yingxue%22">Gao, Yingxue</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bao%2C+Weijie%22">Bao, Weijie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22He%2C+Hong%22">He, Hong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Hongwei%22">Li, Hongwei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hu%2C+Xinyue%22">Hu, Xinyue</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Hailong%22">Li, Hailong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Lianqing%22">Zhang, Lianqing</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Guoping%22">Huang, Guoping</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Xiaoqi%22">Huang, Xiaoqi</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Child+%26+Adolescent+Psychiatry%22">European Child & Adolescent Psychiatry</searchLink>. Nov2025, Vol. 34 Issue 11, p3535-3547. 13p.
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  Data: <searchLink fieldCode="DE" term="%22Diagnosis+of+post-traumatic+stress+disorder%22">Diagnosis of post-traumatic stress disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Sleep+disorder+diagnosis%22">Sleep disorder diagnosis</searchLink><br /><searchLink fieldCode="DE" term="%22Life+change+events%22">Life change events</searchLink><br /><searchLink fieldCode="DE" term="%22Statistical+correlation%22">Statistical correlation</searchLink><br /><searchLink fieldCode="DE" term="%22Functional+connectivity%22">Functional connectivity</searchLink><br /><searchLink fieldCode="DE" term="%22Amygdaloid+body%22">Amygdaloid body</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Questionnaires%22">Questionnaires</searchLink><br /><searchLink fieldCode="DE" term="%22Family+relations%22">Family relations</searchLink><br /><searchLink fieldCode="DE" term="%22Descriptive+statistics%22">Descriptive statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Magnetic+resonance+imaging%22">Magnetic resonance imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Symptoms%22">Symptoms</searchLink><br /><searchLink fieldCode="DE" term="%22Basal+ganglia%22">Basal ganglia</searchLink><br /><searchLink fieldCode="DE" term="%22Families%22">Families</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebral+cortex%22">Cerebral cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Thalamus%22">Thalamus</searchLink><br /><searchLink fieldCode="DE" term="%22Research%22">Research</searchLink><br /><searchLink fieldCode="DE" term="%22Comparative+studies%22">Comparative studies</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis+software%22">Data analysis software</searchLink><br /><searchLink fieldCode="DE" term="%22Psychological+tests%22">Psychological tests</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Psychosocial+factors%22">Psychosocial factors</searchLink><br /><searchLink fieldCode="DE" term="%22Adolescence%22">Adolescence</searchLink>
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  Data: Major depressive disorder (MDD) demonstrates significant alterations in intrinsic functional connectivity (FC) of the subcortical networks (SCN). However, the neurobiological mechanisms underlying these changes in adolescents with MDD and their association with stressors and sleep disturbances remain poorly understood. Using seed-based functional connectivity analysis, we investigated changes in intrinsic connectivity of the SCN in 83 first-episode medication-naïve adolescents with MDD (aMDD) and 59 healthy controls (HC). We then examined the correlation between the SCN connectivity alterations with sleep disturbances and stress factors, measured by the Pittsburgh Sleep Quality Index (PSQI), the Adolescent Life Events Checklist (ASLEC), and the Family Environment Scale-Chinese Version (FES-CV). Compared with HC, aMDD patients showed decreased connectivity between multiple subcortical regions (amygdala, hippocampus, nucleus accumbens (NAc), and thalamus) and cortical regions of the limbic (orbital frontal cortex, inferior temporal gyrus, temporal pole), visual (middle occipital gyrus) and sensorimotor (precentral gyrus) networks. Moreover, we observed that reduced amygdala- and NAc-based FC was correlated with more stress from life events, while reduced thalamus-based FC was associated with more severe sleep disturbances. Our study was the first to comprehensively investigate the SCN-based FC alterations in adolescents with MDD. We revealed disruptions in connectivity between the SCN and cortical networks in aMDD, and further identified potential environmental mechanisms associated with these SCN-based dysconnectivity patterns. These findings underscore critical role of the SCN in the neurobiological mechanisms of aMDD and suggest potential targets for developing novel treatment strategies for adolescents with MDD. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Child & Adolescent Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s00787-025-02774-x
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      – SubjectFull: Sleep disorder diagnosis
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      – SubjectFull: Descriptive statistics
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