Mitochondrial DNA m.13514G>A heteroplasmy is associated with depressive symptoms in the elderly.
Int J Geriatr Psychiatry
; 33(10): 1319-1326, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-29984425
ABSTRACT
OBJECTIVES:
Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at several mtDNA sites in complex I lead to inherited neurological neurologic diseases and brain magnetic resonance imaging (MRI) abnormalities. Here, we test the hypothesis that mtDNA heteroplasmy at these complex I sites is associated with depressive symptoms in the elderly.METHODS:
We examined platelet mtDNA heteroplasmy for associations with depressive symptoms among 137 participants over age 70 from the community-based Health, Aging and Body Composition Study. Depressive symptoms were assessed using the 10-point version of the Center for Epidemiologic Studies Depression Scale (CES-D 10). Complete mtDNA sequencing was performed and heteroplasmy derived for 5 mtDNA sites associated with neurologic mitochondrial diseases and tested for associations with depressive symptoms.RESULTS:
Of 5 candidate complex I mtDNA mutations examined for effects on depressive symptoms, increased heteroplasmy at m.13514A>G, ND5, was significantly associated with higher CES-D score (P = .01). A statistically significant interaction between m.13514A > G heteroplasmy and sex was detected (P = .04); in sex-stratified analyses, the impact of m.13514A>G heteroplasmy was stronger in male (P = .003) than in female (P = .98) participants. Men in highest tertile of mtDNA heteroplasmy exhibited significantly higher (P = .0001) mean ± SE CES-D 10 scores, 5.37 ± 0.58, when compared with those in the middle, 2.13 ± 0.52, and lowest tertiles, 2.47 ± 0.58. No associations between the 4 other candidate sites and depressive symptoms were observed.CONCLUSIONS:
Increased mtDNA heteroplasmy at m.13514A>G is associated with depressive symptoms in older men. Heteroplasmy may represent a novel biological risk factor for depression.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
/
Transtorno Depressivo
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article