| 1. |
- Fernström, Johan, et al.
(författare)
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Plasma circulating cell-free mitochondrial DNA in depressive disorders
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:11
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Fernström, Johan, et al.
(författare)
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Six autoantibodies associated with autoimmune encephalitis are not detectable in the cerebrospinal fluid of suicide attempters
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Previous findings suggest a link between neuroinflammatory processes and suicidality. Despite several lines of evidence supporting this link, including increased pro-inflammatory markers in blood-, cerebrospinal fluid (CSF)- and in post-mortem brain samples from suicidal individuals, the underlying mechanisms remain poorly understood. In this pilot study, we explored the possibility that autoimmune encephalopathies might be found among suicide attempters. We analysed the presence of six different autoantibodies (N-methyl-D-aspartate receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid receptor, the γ-amino-butyric acid B-receptor, the leucine-rich, glioma-inactivated 1, the contactin-associated protein-like 2, and the dipeptidyl-peptidase-like protein-6), all previously associated with psychopathology, in CSF samples from 29 unmedicated suicide attempters. Five of these subjects had high CSF/serum albumin ratio, indicative of increased blood-brain-barrier permeability. We were not able to detect any of these autoantibodies in the CSF samples. These pilot data do not support a role for autoimmune encephalopathies in suicidal behaviour, although the presence of lower levels of these autoantibodies cannot be ruled out in these patients.
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| 3. |
- Grudet, Cécile, et al.
(författare)
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25(OH)D levels are decreased in patients with difficult-to-treat depression
- 2022
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Ingår i: Comprehensive Psychoneuroendocrinology. - : Elsevier BV. - 2666-4976. ; 10, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe aims of the study are i) to compare 25-hydroxyvitamin D (25(OH)D) levels between clinically depressed individuals with insufficient treatment response and healthy controls and ii) to test the association between 25(OH)D levels and different affective disorder diagnoses (i.e., major depressive disorder (MDD) single episode, MDD recurrent episode, chronic MDD, and dysthymia), as well as grade of suicidal ideation.MethodWe quantified serum 25(OH)D in 202 individuals with difficult-to-treat depression (DTD) and 41 healthy controls. Patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR). ANCOVA was used to test differences in mean 25(OH)levels between depressed and controls, adjusting for sex, age, smoking, sampling season, ethnicity, somatic illness, and body mass index (BMI). Binary logistic regression models were used to test the association between depression and 25(OH)D levels.ResultsPatients with difficult-to-treat depression had significantly lower levels of 25(OH)D compared to healthy controls (ANCOVA, F = 4.89; p = 0.03). Thirty percent of the depressed patients were 25(OH)D deficient (<50 nmol/L) compared to 5% of the controls (Chi-squared test, χ2 = 11.38; p < 0.01). The odds for being depressed decreased significantly with 17% per 10 nmol/L increase of 25(OH)D (Binary logistic regression, p < 0.05).LimitationsThe cross-sectional design of the study precludes any conclusions about causality. A large part of the patients took psychotropic drugs and/or had somatic illnesses, which might have affected the results.ConclusionThe results of the present study add to the body of evidence linking 25(OH)D deficiency and depression. Further investigations are warranted to better understand any clinical implications of this association.
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| 4. |
- Grudet, Cécile, et al.
(författare)
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Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood.
- 2014
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 50, s. 210-219
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Tidskriftsartikel (refereegranskat)abstract
- Low levels of vitamin D may play a role in psychiatric disorders, as cross-sectional studies show an association between vitamin D deficiency and depression, schizophrenia and psychotic symptoms. The underlying mechanisms are not well understood, although vitamin D is known to influence the immune system to promote a T helper (Th)-2 phenotype. At the same time, increased inflammation might be of importance in the pathophysiology of depression and suicide. We therefore hypothesized that suicidal patients would be deficient in vitamin D, which could be responsible for the inflammatory changes observed in these patients.
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| 5. |
- Grudet, Cécile, et al.
(författare)
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Vitamin D and inflammation in major depressive disorder
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 267, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased inflammation is reported in Major Depressive Disorder (MDD), which may be more pronounced in suicidal subjects. Vitamin D deficiency may drive this pro-inflammatory state due to vitamin D's anti-inflammatory effects. Methods: We quantified plasma 25-hydroxyvitamin D (25(OH)D) and inflammatory markers interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and other inflammatory indices, neutrophil-to-lymphocyte ratio (NLR) and white blood cell count (WBC) in 48 un-medicated MDD subjects (n = 17 with mild-to-moderate suicidal ideation [SI]) and 54 controls. IL-6 and TNF-α were combined into a composite inflammation score. Results: There were no significant differences in 25(OH)D levels between MDD and controls (p = 0.24) or between MDD with and without SI (p = 0.61). However, 25(OH)D was negatively correlated with all measured inflammatory markers; these correlations were stronger in MDD subjects, and particularly in those with SI. MDD status significantly moderated the relationships between 25(OH)D and NLR (p = 0.03), and 25(OH)D and WBC (p < 0.05), and SI significantly moderated the relationship between 25(OH)D and NLR (p = 0.03). Limitations: The study was cross-sectional, thereby limiting causal inference, and had a small sample size. Only seventeen of the MDD subjects had SI. Conclusion: While 25(OH)D levels did not significantly differ in MDD vs. controls, or in MDD with or without SI, lower 25(OH)D was associated with indices of immune activation in MDD, especially in cases with SI. Although our findings do not address causality, they are consistent with findings that relatively low 25(OH)D levels in MDD are associated with a pro-inflammatory state.
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| 6. |
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| 7. |
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| 8. |
- Håkansson, Anders, et al.
(författare)
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Decreasing Psychiatric Emergency Visits, but Stable Addiction Emergency Visits, During COVID-19—A Time Series Analysis 10 Months Into the Pandemic
- 2021
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 9. |
- Håkansson, Anders, et al.
(författare)
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No apparent increase in treatment uptake for gambling disorder during ten months of the covid-19 pandemic—analysis of a regional specialized treatment unit in Sweden
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:4, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic and its impact on society has been suspected to affect gambling behaviors. Potentially, the pandemic crisis may result in increased problem gambling, for example, due to COVID-19-related psychological distress, unemployment, and financial difficulties. In ad-dition, the cancellation of sports in early parts of the crisis has been suspected to alter gambling behaviors. Policy makers have called for action and, in some cases, have changed regulations, and media have reported possible increases in treatment seeking. However, research data are hitherto lacking. The present study assessed the treatment uptake at a regional specialized gambling-disorder unit in the healthcare system of Region Skåne, Sweden. Number of patients, treatment contacts, and patterns of rescheduling or cancellations of appointments were quantified for each month, January– December 2020, and compared to corresponding months of 2018 and 2019. Possible trends were analyzed, using an interrupted time-series analysis. Results did not indicate an increase in treatment uptake for gambling disorder during the months of COVID-19 impact in Sweden. The proportion of digital treatment increased, but total treatment uptake was unaffected by the pandemic. In conclusion, during the first ten months of the pandemic in Sweden, no obvious increase in treatment uptake for gambling disorder could be seen. Moreover, longer follow-up may be necessary in order to see if effects of worsening socioeconomic conditions may be a possible long-term risk factor of increased gambling after COVID-19.
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| 10. |
- 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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