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.
The suicide attempters in our study were deficient in vitamin D. Our data also suggest that vitamin D deficiency could be a contributing factor to the elevated pro-inflammatory cytokines previously reported in suicidal patients. We propose that routine clinical testing of vitamin D levels could be beneficial in patients with suicidal symptoms, with subsequent supplementation in patients found to be deficient.
Background Plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule and a novel biomarker of psychiatric disorders. Some previous studies reported increased levels of ccf-mtDNA in unmedicated depression and recent suicide attempters, while other studies found unchanged or decreased ccf-mtDNA levels in depression. Inconsistent findings across studies may be explained by small sample sizes and between-study variations in somatic and psychiatric co-morbidity or medication status. Methods We measured plasma ccf-mtDNA in a cohort of 281 patients with depressive disorders and 49 healthy controls. Ninety-three percent of all patients were treated with one or several psychotropic medications. Thirty-six percent had a personality disorder, 13% bipolar disorder. All analyses involving ccf-mtDNA were a priori adjusted for age and sex. Results Mean levels in ccf-mtDNA were significantly different between patients with a current depressive episode (n = 236), remitted depressive episode (n = 45) and healthy controls (n = 49) (f = 8.3, p<0.001). Post-hoc tests revealed that both patients with current (p<0.001) and remitted (p = 0.002) depression had lower ccf-mtDNA compared to controls. Within the depressed group there was a positive correlation between ccf-mtDNA and “inflammatory depression symptoms” (r = 0.15, p = 0.02). We also found that treatment with mood stabilizers lamotrigine, valproic acid or lithium was associated with lower ccf-mtDNA (f = 8.1, p = 0.005). Discussion Decreased plasma ccf-mtDNA in difficult-to-treat depression may be partly explained by concurrent psychotropic medications and co-morbidity. Our findings suggest that ccf-mtDNA may be differentially regulated in different subtypes of depression, and this hypothesis should be pursued in future studies.
Background: The COVID-19 pandemic has been suspected to increase mental health problems, but also to possibly lead to a decreased treatment seeking, for example due to fear of attending hospital. Early findings demonstrate decreased treatment seeking for mental health, which may differ across diagnostic groups. This study aimed to examine treatment uptake at a general psychiatry emergency unit and at an addiction psychiatry emergency unit in Malmö, Sweden, separately. In addition, the study aimed to investigate treatment uptake for different diagnostic groups—during and prior to the COVID-19 pandemic.Methods: Monthly data for number of unique patients and number of contacts were extracted for the three-year period of January 2018 through December 2020. Data from each facility were analyzed separately for women, men and patients with psychotic, affective, anxiety and substance use-related disorders. Interrupted time series were used to demonstrate possible effects of COVID-19.Results: COVID-19 was associated with a marked decrease in treatment contacts, both for women and men, in the general psychiatry emergency unit—driven by a significant decrease in anxiety-related disorders (p < 0.001) and affective disorders (p < 0.01)—but not in psychotic or substance use disorders (SUDs). Also, in the addiction psychiatry emergency unit, no significant impact of COVID-19 was seen.Conclusions: COVID-19 may decrease treatment uptake for acute affective and anxiety-related disorders. Given the hypothesized increase in the population regarding these conditions, societal efforts are needed to facilitate adequate treatment for these patients during the COVID-19 pandemic. Society should also remain vigilant with respect to SUDs during the pandemic.
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