Overweight and POMC methylation: epigenetic associations with adolescent depression

Abstract Introduction To evaluate whether BMI status influences POMC methylation levels and subsequently affects the course of adolescent depression. This study examined the relationship between the methylation levels of different CpG sites in the POMC gene and clinical symptoms across various BMI c...

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Main Authors: Ye Ye, Jia-Hui Hu, Xing-Yu Xiao, Ting Ji, Fei Wang, Fu-Jun Jia, Cai-Lan Hou
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-07162-y
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author Ye Ye
Jia-Hui Hu
Xing-Yu Xiao
Ting Ji
Fei Wang
Fu-Jun Jia
Cai-Lan Hou
author_facet Ye Ye
Jia-Hui Hu
Xing-Yu Xiao
Ting Ji
Fei Wang
Fu-Jun Jia
Cai-Lan Hou
author_sort Ye Ye
collection DOAJ
description Abstract Introduction To evaluate whether BMI status influences POMC methylation levels and subsequently affects the course of adolescent depression. This study examined the relationship between the methylation levels of different CpG sites in the POMC gene and clinical symptoms across various BMI categories in adolescent depression. Methods A total of 108 adolescent patients with depressive disorders including 68 with unipolar depression and 40 with bipolar depression participated in the study. They were divided into three groups: 11 underweight individuals (BMI below the age-specific threshold), 75 normal-weight individuals (BMI within the defined normal range), and 22 overweight individuals (BMI between the overweight threshold and obesity threshold). Pyrosequencing methylation analysis was used to assess POMC gene promoter methylation levels Results Adolescents in the overweight group exhibited significantly lower methylation levels at CpG6 and CpG8 of the POMC gene compared to their normal-weight and underweight peers. Furthermore, methylation at these sites was associated with clinical and psychological indicators such as Childhood Trauma Questionnaire (CTQ) and Montgomery–Asberg Depression Rating Scale (MADRS) scores. After adjusted for medication use, multivariate linear regression analysis revealed a negative correlation between CpG6 methylation levels and CTQ scores in overweight group. Conclusion This study shows the association between POMC methylation levels and depressive symptoms in adolescents across different BMI categories. The findings suggest a potential interaction between epigenetic mechanisms, depression and overweight providing a foundation for further mechanistic investigations. Trial registration Not applicable.
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institution Kabale University
issn 1471-244X
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series BMC Psychiatry
spelling doaj-art-4f0bab68c001462b8dbf84717bd341232025-08-20T03:43:01ZengBMCBMC Psychiatry1471-244X2025-07-0125111010.1186/s12888-025-07162-yOverweight and POMC methylation: epigenetic associations with adolescent depressionYe Ye0Jia-Hui Hu1Xing-Yu Xiao2Ting Ji3Fei Wang4Fu-Jun Jia5Cai-Lan Hou6Guangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityGuangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityLanzhou University Second HospitalInternal Medicine Department, Guangdong Women and Children HospitalGuangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityGuangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityGuangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityAbstract Introduction To evaluate whether BMI status influences POMC methylation levels and subsequently affects the course of adolescent depression. This study examined the relationship between the methylation levels of different CpG sites in the POMC gene and clinical symptoms across various BMI categories in adolescent depression. Methods A total of 108 adolescent patients with depressive disorders including 68 with unipolar depression and 40 with bipolar depression participated in the study. They were divided into three groups: 11 underweight individuals (BMI below the age-specific threshold), 75 normal-weight individuals (BMI within the defined normal range), and 22 overweight individuals (BMI between the overweight threshold and obesity threshold). Pyrosequencing methylation analysis was used to assess POMC gene promoter methylation levels Results Adolescents in the overweight group exhibited significantly lower methylation levels at CpG6 and CpG8 of the POMC gene compared to their normal-weight and underweight peers. Furthermore, methylation at these sites was associated with clinical and psychological indicators such as Childhood Trauma Questionnaire (CTQ) and Montgomery–Asberg Depression Rating Scale (MADRS) scores. After adjusted for medication use, multivariate linear regression analysis revealed a negative correlation between CpG6 methylation levels and CTQ scores in overweight group. Conclusion This study shows the association between POMC methylation levels and depressive symptoms in adolescents across different BMI categories. The findings suggest a potential interaction between epigenetic mechanisms, depression and overweight providing a foundation for further mechanistic investigations. Trial registration Not applicable.https://doi.org/10.1186/s12888-025-07162-yPOMCDepressionMethylationBMIOverweight
spellingShingle Ye Ye
Jia-Hui Hu
Xing-Yu Xiao
Ting Ji
Fei Wang
Fu-Jun Jia
Cai-Lan Hou
Overweight and POMC methylation: epigenetic associations with adolescent depression
BMC Psychiatry
POMC
Depression
Methylation
BMI
Overweight
title Overweight and POMC methylation: epigenetic associations with adolescent depression
title_full Overweight and POMC methylation: epigenetic associations with adolescent depression
title_fullStr Overweight and POMC methylation: epigenetic associations with adolescent depression
title_full_unstemmed Overweight and POMC methylation: epigenetic associations with adolescent depression
title_short Overweight and POMC methylation: epigenetic associations with adolescent depression
title_sort overweight and pomc methylation epigenetic associations with adolescent depression
topic POMC
Depression
Methylation
BMI
Overweight
url https://doi.org/10.1186/s12888-025-07162-y
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