| 1. |
- Bersani, Francesco S, et al.
(författare)
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Association of dimensional psychological health measures with telomere length in male war veterans.
- 2016
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 190, s. 537-542
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Tidskriftsartikel (refereegranskat)abstract
- Several psychiatric disorders may be characterized by peripheral telomere shortening. However, it is unclear whether telomere shortening is associated with these psychiatric disorders per se or, rather, with underlying dimensional parameters that are often, but not necessarily, associated with them. We explored the association between dimensional psychopathological measures and telomere length (TL) in granulocytes among veterans independent of psychiatric diagnosis.
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| 2. |
- Bersani, Francesco Saverio, et al.
(författare)
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Mitochondrial DNA copy number is reduced in male combat veterans with PTSD.
- 2016
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Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846. ; 64:Jun 25, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial abnormalities may be involved in PTSD, although few studies have examined this. Mitochondrial DNA copy number (mtDNAcn) in blood cells is an emerging systemic index of mitochondrial biogenesis and function. The present study assessed mtDNAcn in male combat-exposed veterans with PTSD compared to those without PTSD as well as its correlation with clinical scales.
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| 3. |
- Blalock, Zachary N., et al.
(författare)
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Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD
- 2024
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Ingår i: Translational Psychiatry. - 2158-3188. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohen’s d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η 2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = −0.171, p = 0.020) and cortisol decline (r = −0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.
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| 4. |
- Fernström, Johan, et al.
(författare)
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Blood-based mitochondrial respiratory chain function in major depression
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.
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| 5. |
- Jué, Sarah, et al.
(författare)
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Enhancing wood UV stability: novel treatment strategies with citric acid and urea
- 2024
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Ingår i: Wood Material Science & Engineering. - : Taylor & Francis. - 1748-0272 .- 1748-0280. ; 19:4, s. 993-996
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Tidskriftsartikel (refereegranskat)abstract
- Wood, a fundamental material in construction, confronts durability and weathering challenges, notably UV-induced degradation leading to colour changes. This study investigated a novel treatment using citric acid and urea to enhance the UV stability of wood. The reaction between these compounds generates water-soluble fluorescent species and insoluble particles upon thermal treatment which may provide wood with UV protection. Specimens were treated with two different treatment methods and then exposed to 2016 h of accelerated weathering, during which colour was measured regularly. Citric acid and urea were either pressure impregnated into the wood and thermally reacted in situ during heat treatment or pre-reacted in the absence of wood with subsequent implementation into melamine formaldehyde (MF) and water-based surface coatings. The results showed that water-soluble fluorophore compounds were formed with both treatment methods. Accelerated weathering tests revealed significant colour changes over time, where specimens coated with a mixture of MF and fluorescent particles from the reaction between citric acid and urea, exhibiting the least alteration. The lowest colour change ΔE of 5.9 was observed for specimens coated with a MF-based coating containing 1 wt% of citric acid and urea thermally pre-reacted at a temperature of 180 °C, showcasing potential wood protection applications.
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| 6. |
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| 7. |
- Lindqvist, Daniel, et al.
(författare)
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Circulating Cell-Free Mitochondrial DNA - a Novel Marker of Mitochondrial Stress Associated With Suicidality and Major Depressive Disorder
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:9, suppl. 1, s. S25-S26
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Mitochondrial DNA copy number (mtDNA-cn), which represents the number of mitochondrial genomes per cell, can be quantified in peripheral blood mononuclear cells (PBMC) and is thought to reflect variations in mitochondrial biogenesis. Additionally, mtDNA may be released at low levels into the circulation from mitochondria under cellular stress, resulting in circulating cell-free mtDNA (ccf-mtDNA) detectable in plasma. The source or physiological significance of ccf-mtDNA in psychiatric illness is unknown but may reflect cell damage, cell death, or bioenergetic compromise. Methods: We enrolled suicide attempters (across diagnoses), non-suicidal subjects with Major Depressive Disorder (MDD), and healthy controls (all medication-free) in two independent cohorts (n=110 & n=74). MtDNA was quantified in cell-free plasma and in PBMCs. Results: Ccf-mtDNA was elevated in suicide attempters and in non-suicidal MDD subjects, compared to healthy controls. These group effects were very large (Cohen’s d ranging from 0.9 to 4.0, all p<0.00001). Ccf-mtDNA and cellular PBMC mtDNA-cn were not significantly correlated with each other (r=0.02, p=0.87), suggesting they reflect different processes. Ccf-mtDNA correlated with post-dexamethasone cortisol (r=0.5, p<0.001), suggesting that HPA-axis hyperactivity may be associated with cellular damage and release of ccf-mtDNA into the blood. Ccf-mtDNA also directly correlated with the antioxidant enzyme glutathione peroxidase (r=0.32, p=0.001), possibly reflecting a compensatory attempt to upregulate antioxidant defence mechanisms due to cellular stress. Conclusions: Ccf-mtDNA may represent a novel marker of cellular stress, which is increased in certain psychiatric conditions. These results call for replication in larger cohorts and in longitudinal studies.
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| 8. |
- Lindqvist, Daniel, et al.
(författare)
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Circulating cell-free mitochondrial DNA, but not leukocyte mitochondrial DNA copy number, is elevated in major depressive disorder
- 2018
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 43:7, s. 1557-1564
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) has been linked to mitochondrial defects, which could manifest in mitochondrial DNA (mtDNA) polymorphisms or mutations. Additionally, copy number of mtDNA (mtDNA-cn) can be quantified in peripheral blood mononuclear cells (PBMC)s, indirectly reflecting cellular energetics, or in the circulating cell-free mtDNA (ccf-mtDNA) levels, which may reflect a fraction of the mitochondrial genome released during cellular stress. Few studies have examined ccf-mtDNA in MDD, and no studies have tested its relationship with intracellular mtDNA-cn or with antidepressant treatment response. Here, mtDNA levels were quantified in parallel from: (i) PBMCs and (ii) cell-free plasma of 50 unmedicated MDD subjects and 55 controls, in parallel with PBMC telomere length (TL) and antioxidant enzyme glutathione peroxidase (GpX) activity. MtDNA measures were repeated in 19 MDD subjects after 8 weeks of open-label SSRI treatment. In analyses adjusted for age, sex, BMI, and smoking, MDD subjects had significantly elevated levels of ccf-mtDNA (F = 20.6, p = 0.00002). PBMC mtDNA-cn did not differ between groups (p > 0.4). In preliminary analyses, we found that changes in ccf-mtDNA with SSRI treatment differed between SSRI responders and non-responders (F = 6.47, p = 0.02), with the non-responders showing an increase in ccf-mtDNA and responders not changing. Baseline ccf-mtDNA was positively correlated with GpX (r = 0.32, p = 0.001), and PBMC mtDNA correlated positively with PBMC TL (r = 0.38, p = 0.0001). These data suggest that plasma ccf-mtDNA and PBMC mtDNA-cn reflect different cellular processes and that the former may be more reflective of certain aspects of MDD pathophysiology and of the response to SSRI antidepressants.
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| 9. |
- Lindqvist, Daniel, et al.
(författare)
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Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.
- 2015
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634. ; 55:May 18, s. 333-364
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Forskningsöversikt (refereegranskat)abstract
- Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.
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| 10. |
- Tymofiyeva, Olga, et al.
(författare)
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High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression
- 2018
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Ingår i: Journal of Affective Disorders. - Amsterdam : Elsevier. - 0165-0327 .- 1573-2517. ; 232, s. 283-290
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adolescent anxiety and depression are highly prevalent psychiatric disorders that are associated with altered molecular and neurocircuit profiles. Recently, increased mitochondrial DNA copy number (mtDNA-cn) has been found to be associated with several psychopathologies in adults, especially anxiety and depression. The associations between mtDNA-cn and anxiety and depression have not, however, been investigated in adolescents. Moreover, to date there have been no studies examining associations between mtDNA-cn and brain network alterations in mood disorders in any age group.METHODS: The first aim of this study was to compare salivary mtDNA-cn between 49 depressed and/or anxious adolescents and 35 well-matched healthy controls. The second aim of this study was to identify neural correlates of mtDNA-cn derived from diffusion tensor imaging (DTI) and tractography, in the full sample of adolescents.RESULTS: There were no diagnosis-specific alterations in mtDNA-cn. However, there was a positive correlation between mtDNA-cn and levels of anxiety, but not depression, in the full sample of adolescents. A subnetwork of connections largely corresponding to the left fronto-occipital fasciculus had significantly lower fractional anisotropy (FA) values in adolescents with higher than median mtDNA-cn.LIMITATIONS: Undifferentiated analysis of free and intracellular mtDNA and use of DTI-based tractography represent this study's limitations.CONCLUSIONS: The results of this study help elucidate the relationships between clinical symptoms, molecular changes, and neurocircuitry alterations in adolescents with and without anxiety and depression, and they suggest that increased mtDNA-cn is associated both with increased anxiety symptoms and with decreased fronto-occipital structural connectivity in this population.
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| 11. |
- Verhoeven, Josine E, et al.
(författare)
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Epigenetic Age in Male Combat-Exposed War Veterans : Associations with Posttraumatic Stress Disorder Status
- 2018
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Ingår i: Molecular Neuropsychiatry. - : S. Karger AG. - 2296-9209. ; 4:2, s. 90-99
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation patterns change with age and can be used to derive an estimate of "epigenetic age," an indicator of biological age. Several studies have shown associations of posttraumatic stress disorder (PTSD) with worse somatic health and early mortality, raising the possibility of accelerated biological aging. This study examined associations between estimated epigenetic age and various variables in 160 male combat-exposed war veterans with (n = 79) and without PTSD (n = 81). DNA methylation was assessed in leukocyte genomic DNA using the Illumina 450K DNA methylation arrays. Epigenetic age was estimated using Horvath's epigenetic clock algorithm and Δage (epigenetic age-chronological age) was calculated. In veterans with PTSD (Δage = 3.2), Δage was on average lower compared to those without PTSD (Δage = 5.0; p = 0.02; Cohen's d = 0.42). This between-group difference was not explained by race/ethnicity, lifestyle factors or childhood trauma. Antidepressant use, however, explained part of the association. In the PTSD positive group, telomerase activity was negatively related to Δage (β = -0.35; p = 0.007). In conclusion, veterans with PTSD had significantly lower epigenetic age profiles than those without PTSD. Further, current antidepressant use and higher telomerase activity were related to relatively less epigenetic aging in veterans with PTSD, speculative of a mechanistic pathway that might attenuate biological aging-related processes in the context of PTSD.
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| 12. |
- Wolkowitz, Owen M, et al.
(författare)
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PBMC telomerase activity, but not leukocyte telomere length, correlates with hippocampal volume in major depression.
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0925-4927. ; 232:1, s. 58-64
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated cell aging, indexed in peripheral leukocytes by telomere shortness and in peripheral blood mononuclear cells (PBMCs) by telomerase activity, has been reported in several studies of major depressive disorder (MDD). However, the relevance of these peripheral measures for brain indices that are presumably more directly related to MDD pathophysiology is unknown. In this study, we explored the relationship between PBMC telomerase activity and leukocyte telomere length and magnetic resonance imaging-estimated hippocampal volume in un-medicated depressed individuals and healthy controls. We predicted that, to the extent peripheral and central telomerase activity are directly related, PBMC telomerase activity would be positively correlated with hippocampal volume, perhaps due to hippocampal telomerase-associated neurogenesis, neuroprotection or neurotrophic facilitation, and that this effect would be clearer in individuals with increased PBMC telomerase activity, as previously reported in un-medicated MDD. We did not have specific hypotheses regarding the relationship between leukocyte telomere length and hippocampal volume, due to conflicting reports in the published literature. We found, in 25 un-medicated MDD subjects, that PBMC telomerase activity was significantly positively correlated with hippocampal volume; this relationship was not observed in 18 healthy controls. Leukocyte telomere length was not significantly related to hippocampal volume in either group (19 unmedicated MDD subjects and 17 healthy controls). Although the nature of the relationship between peripheral telomerase activity and telomere length and the hippocampus is unclear, these preliminary data are consistent with the possibility that PBMC telomerase activity indexes, and may provide a novel window into, hippocampal neuroprotection and/or neurogenesis in MDD.
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| 13. |
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