Assessing the joint effects of mitochondrial function and human behavior on the risks of anxiety and depression

Zhang, Huijie; Chen, Yujing; Zhang, Jingxi; Li, Chune; Zhang, Zhen; Pan, Chuyu; Cheng, Shiqiang; Yang, Xuena; Meng, Peilin; Jia, Yumeng; Wen, Yan; Liu, Huan; Zhang, Feng

doi:10.1016/j.jad.2022.09.157

Cited by 3 publications

(2 citation statements)

References 65 publications

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“…However, rare previous studies have ever investigated potential sex differences in mtDNA under anxiety-related or depression-related psychiatric illness. A previous study from our group confirmed the potential sex-related differences in the associations between mitochondrial function and human behavior interactions and anxiety/depression [ 54 ]. We found mtDNA × CRP interactions differed in male, female and total subjects with anxiety or depression.…”

Section: Discussionsupporting

confidence: 75%

Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression

Liu,

Cheng,

et al. 2023

Transl Psychiatry

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The aim of this study was to investigate the possible interaction of mitochondrial dysfunction and inflammatory cytokines in the risk of anxiety and depression. We utilized the UK Biobank for the sample of this study. A mitochondria-wide association(MiWAS) and interaction analysis was performed to investigate the interaction effects of mitochondrial DNA (mtDNA)×C-reactive protein (CRP) on the risks of self-reported anxiety (N = 72,476), general anxiety disorder (GAD-7) scores (N = 80,853), self-reported depression (N = 80,778), Patient Health Questionnaire (PHQ-9) scores (N = 80,520) in total samples, females and males, respectively, adjusting for sex, age, Townsend deprivation index (TDI), education score, alcohol intake, smoking and 10 principal components. In all, 25 mtSNPs and 10 mtSNPs showed significant level of association with self-reported anxiety and GAD-7 score respectively. A total of seven significant mtDNA × CRP interactions were found for anxiety, such as m.3915G>A(MT-ND1) for self-reported anxiety in total subjects (P = 6.59 × 10−3), m.4561T>C(MT-ND2) (P = 3.04 × 10−3) for GAD-7 score in total subjects. For depression, MiWAS identified 17 significant mtSNPs for self-reported depression and 14 significant mtSNPs for PHQ-9 scores. 17 significant mtDNA associations (2 for self-reported depression and 15 for PHQ-9 score) was identified, such as m.14869G>A(MT-CYB; P = 2.22 × 10−3) associated with self-reported depression and m.4561T>C (MT-ND2; P value = 3.02 × 10−8) associated with PHQ-9 score in all subjects. In addition, 5 common mtDNA shared with anxiety and depression were found in MiWAS, and 4 common mtDNA variants were detected to interact with CRP for anxiety and depression, such as m.9899T>C(MT-CO3). Our study suggests the important interaction effects of mitochondrial function and CRP on the risks of anxiety and depression.

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Section: Discussionsupporting

confidence: 75%

Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression

Liu,

Cheng,

et al. 2023

Transl Psychiatry

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“…An integrative gene set enrichment analysis spotlighted the prominence of mitochondrial-centric genes in both the bed nucleus of the stria terminalis and the blood of stressexposed mice. Additionally, the intertwined effects of mitochondrial functionality and human behaviors on anxiety and depression risks were examined [28]. It found a positive association between mitochondrial heteroplasmy against drinking and the risks of anxiety and depression.…”

Section: Depression and Anxietymentioning

confidence: 99%

Exploring the Interplay between Mitochondrial DNA and Lifestyle Factors in the Pathogenesis of Psychiatric Disorders

Wei,

Cheng,

Zhao

et al. 2024

Depression and Anxiety

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The objectives of this study were to investigate the interaction of mitochondrial DNA (mtDNA) and lifestyle factors in the development of psychiatric disorders and to gain greater insight into their pathogenesis and comorbidity. We analyzed data from approximately 150,000 individuals from the UK Biobank. Mitochondrial gene-by-environment interaction studies (mtGEIS) were performed to assess the relationships between mtDNA and psychiatric disorders, such as anxiety, depression, and self-harm. These disorders were defined using diagnostic and severity indicators derived from the General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9). Smoking and drinking behaviors were characterized based on UK Biobank criteria. For the mtGEIS, logistic and linear regression models from PLINK 2.0 were employed, accounting for covariates like age, sex, PC1-10, Townsend Deprivation Index (TDI), and educational attainment. We also conducted sex-stratified analyses to detect any gender-specific effects. Our findings highlighted significant associations between mtDNA and three psychiatric disorders. Moreover, the interplay between mtDNA and lifestyle factors showed significant associations with psychiatric disorders (all P values < 0.05). Specifically, two mutant loci, T5004C (BAnx_self=−0.0026, BDep_self=−0.0024, BSelf−harm=−0.0018) and G9123A (BAnx_self=−0.0030, BDep_self=−0.0024, BSelf−harm=−0.0017), were found to reduce the risk of three disorders after interacting with alcohol. Sex-specific differences were also observed. In summary, the expression of mitochondrial genes could be modulated by lifestyle factors like smoking and drinking, potentially affecting psychiatric disorders. These habits might influence mitochondrial respiratory chain activity and the replication and transcriptional regulation of mitochondrial genes, culminating in changes in mitochondrial functionality and subsequently psychiatric disorders.

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Addressing global cognition and ineffective depressogenic discrimination strategies with clinical hypnosis

Yapko

2023

American Journal of Clinical Hypnosis

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Assessing the joint effects of mitochondrial function and human behavior on the risks of anxiety and depression

Cited by 3 publications

References 65 publications

Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression

Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression

Exploring the Interplay between Mitochondrial DNA and Lifestyle Factors in the Pathogenesis of Psychiatric Disorders

Addressing global cognition and ineffective depressogenic discrimination strategies with clinical hypnosis

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