Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity
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Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic–pituitary–adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-values<2.98E−12, Cohen’s d ranging from 2.55 to 4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho=0.49,P<0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.
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Free circulating mtDNA measured via blood plasma was significantly higher in individuals with a history of suicide attempt than in healthy controls.
“free circulating mtDNA measured via blood plasma was significantly higher in individuals with a history of suicide attempt compared with healthy controls (Lindqvist et al. 2016)”
From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as Lindqvist et al. 2016
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- Authors
- Lindqvist, D., Fernström, J., Grudet, C., Ljunggren, L., Träskman-Bendz, L., Ohlsson, L., & Westrin, Å.
- Affiliations
- University of California, San Francisco (US)
- Lund University (SE)
- Malmö University (SE)
- Corresponding author
- Ohlsson, L
- Venue
- Translational Psychiatry
- Published
- 2016-12-06
- Volume
- 6
- Issue
- 12
- Pages
- e971-e971
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC5315562
- OpenAlex
- W2560494659
- Cited by
- 111
- References
- 59
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 13 · 2022: 11 · 2021: 15 · 2020: 11 · 2019: 16 · 2018: 10 · 2017: 4
- FWCI
- 13.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Malmö University Publications (Malmö University) (submittedVersion)
- Funders
- Vetenskapsrådet (INCA 600398, 2015-00387)
- Institut National Du Cancer (600398)
- Svenska Läkaresällskapet
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- circulating cell-free mitochondrial DNA, suicide attempters, dexamethasone suppression test, cortisol, chronic stress, mitochondrial dysfunction, suicidal behavior, depression
- MeSH terms
- Cell-Free Nucleic Acids, Adult, Depressive Disorder, Major, Major Depressive Disorder, DNA, Mitochondrial, Female, Humans, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Suicide, Attempted, Case-Control Studies
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