| 1. |
- Ambrus, Livia, et al.
(författare)
-
Hypothalamic–pituitary–adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters
- 2016
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 70:8, s. 575-581
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic–pituitary–adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. Method: Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items ‘Concentration difficulties’ and ‘Failing memory’ were extracted. Results: Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = −0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = −0.372, p = 0.020). Conclusion: The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.
|
|
| 2. |
- Erhardt, Sophie, et al.
(författare)
-
Connecting Inflammation with Glutamate Agonism in Suicidality
- 2013
-
Ingår i: Neuropsychopharmacology. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0893-133X .- 1740-634X. ; 38:5, s. 743-752
-
Tidskriftsartikel (refereegranskat)abstract
- The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (Pandlt;0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. Neuropsychopharmacology (2013) 38, 743-752; doi:10.1038/npp.2012.248; published online 9 January 2013
|
|
| 3. |
- Fernström, Johan, et al.
(författare)
-
Six autoantibodies associated with autoimmune encephalitis are not detectable in the cerebrospinal fluid of suicide attempters
- 2017
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
-
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.
|
|
| 4. |
- Lindqvist, Daniel, et al.
(författare)
-
CSF biomarkers in suicide attempters - a principal component analysis.
- 2011
-
Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 1600-0447 .- 0001-690X. ; 124, s. 52-61
-
Tidskriftsartikel (refereegranskat)abstract
- Lindqvist D, Janelidze S, Erhardt S, Träskman-Bendz L, Engström G, Brundin L. CSF biomarkers in suicide attempters - a principal component analysis. Objective: The objective of the present study was to identify biological patterns (factors) among 20 cerebrospinal fluid (CSF) biomarkers in suicide attempters and subsequently analyse their association with suicidal behaviour. Method: We measured kynurenic acid, orexin, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol, chemokines, matrix metalloproteases and cytokines in the CSF of 124 drug-free suicide attempters. Patients were evaluated for suicidality and psychiatric symptoms using well-defined psychiatric rating scales and followed-up regarding future suicide. We used principal component analysis to identify factors among the biological substances. Results: Four factors were extracted from the 20 biomarkers, explaining 52.4% of the total variance. Factors 1 and 2 were characterized by high loadings of chemokines and cytokines respectively. They were both associated with severe depressive symptoms. Factor 2 was also associated with a high suicidal intent. Factor 4 was characterized by strong loadings of the monoamine metabolites 5-HIAA and HVA, as well as orexin and interleukin-6. High scores on this factor were found in patients who performed a violent suicide attempt and in patients who subsequently completed suicide. Conclusion: Our results suggest that specific combinations of CSF biomarkers may discriminate between types of suicidal behaviour and indicate increased risk for future suicide.
|
|
| 5. |
- Lindqvist, Daniel, et al.
(författare)
-
Increased Plasma Levels of Circulating Cell-Free Mitochondrial DNS in Suicide Attempters - Associations with HPA-Axis Hyperactivity
- 2017
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 81:10, s. S228-S228
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: 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, but no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample.Methods: 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 associated with hypothalamic pituitary adrenal (HPA)-axis hyperactivity. Results: Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared to healthy controls at different time points (pre- and post-DST) (all p-values ,2.98E-12, Cohen’s d ranging from 2.55-4.01). Pre-DST plasma levels of mtDNA were positively correlated with postDST cortisol levels (rho50.49, p,0.003).Conclusions: 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 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 freecirculating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.
|
|
| 6. |
- Lindqvist, Daniel, et al.
(författare)
-
Interleukin-6 Is Elevated in the Cerebrospinal Fluid of Suicide Attempters and Related to Symptom Severity
- 2009
-
Ingår i: BIOLOGICAL PSYCHIATRY. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 66:3, s. 287-292
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Depressive disorders are associated with immune system alterations that can be detected in the blood. Cytokine concentrations in cerebrospinal fluid (CSF) and their relationship to aspects of suicidality have previously not been investigated. Methods: We measured interleukin-1 beta interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-a (TNF-alpha) in CSF and plasma of suicide attempters (n = 63) and healthy control subjects (n = 47). Patients were classified according to diagnosis and violent or nonviolent suicide attempt. We evaluated suicidal ideation and depressive symptoms using the Suicide Assessment Scale and the Montgomery-Asberg Depression Rating Scale (MADRS). We also analyzed the relation between cytokines and monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in CSF, as well as the integrity of the blood-brain barrier as reflected by the CSF:serum albumin ratio. Results: IL-6 in CSF was significantly higher in suicide attempters than in healthy control subjects. Patients who performed violent suicide attempts displayed the highest IL-6. Furthermore, there was a significant positive correlation between MANS scores and CSF IL-6 levels in all patients. IL-6 and TNF-a correlated significantly with 5-HIAA and HVA in CSF, but not with MHPG. Cytokine levels in plasma and CSF were not associated, and patients with increased blood-brain barrier permeability did not exhibit elevated cytokine levels. Conclusions: We propose a role for CSF IL-6 in the symptomatology of suicidal behavior, possibly through mechanisms involving alterations of dopamine and serotonin metabolism.
|
|
| 7. |
- Lindqvist, Daniel, et al.
(författare)
-
Salivary cortisol and suicidal behavior-A follow-up study.
- 2008
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 33:8, s. 1061-1068
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis is a common finding in major depressive disorder. Similar studies on suicide attempters are less abundant, and the results are divergent. The main aim of the present study was to investigate HPA-axis parameters by the time of a suicide attempt and at follow-up in search for associations between HPA-axis function and suicidal behavior. METHODS: Thirty-five suicide attempters and 16 non-suicidal controls were admitted to a psychiatric ward between the years of 1986 and 1992. Corticotrophin-releasing hormone (CRH) in cerebrospinal fluid and urinary cortisol were obtained for the suicide attempters. The patients were followed up approximately 12 years after the index admission. Cortisol was measured in saliva, and additional suicide attempts and current psychiatric symptoms were registered. RESULTS: At follow-up, evening salivary cortisol was lower in suicide attempters compared to controls. Low cortisol levels at follow-up were associated with severe psychiatric symptoms. Among women, repeated suicide attempts were associated with low morning and lunch salivary cortisol, and in this subgroup we also found significant correlations between salivary cortisol at follow-up, and CRH as well as urinary cortisol at index. CONCLUSION: We found evidence for an association between low HPA-axis activity and suicidal behavior. This could be due to long-lasting and severe psychiatric morbidity, which in turn has exhausted the HPA-axis of these patients. The potential role of hypocortisolism should be given more attention in studies on suicidal patients.
|
|
| 8. |
- Lindqvist, Daniel, et al.
(författare)
-
Suicidal intent and psychiatric symptoms among inpatient suicide attempters.
- 2007
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 61:1, s. 27-32
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate associations between suicidal intent and psychiatric symptoms, and to study the usefulness of the Suicidal Intent Scale (SIS) and the Comprehensive Psychopathological Rating Scale (CPRS) for suicide risk assessment in an inpatient population. One hundred and ninety-six suicide attempters, of whom 15 eventually committed suicide, were admitted to a psychiatric ward. They were assessed by means of the SIS and the CPRS. Cox regression analyses were performed in order to adjust the relationships between the individual CPRS subscales and suicide for age and gender. The patients who later completed suicide had higher scores on the CPRS than the patients who did not complete suicide. We found no associations between symptoms and suicidal intent. The severity of psychopathology, in terms of high CPRS scores, shows a stronger association with future suicide than the level of suicidal intent (SIS) among inpatient suicide attempters. Suicidal intent is evidently scored regardless of psychiatric symptoms.
|
|
| 9. |
- Lindqvist, Daniel, et al.
(författare)
-
Suicidal Intent and the HPA-Axis Characteristics of Suicide Attempters with Major Depressive Disorder and Adjustment Disorders.
- 2008
-
Ingår i: Archives of Suicide Research. - : Informa UK Limited. - 1543-6136 .- 1381-1118. ; 12:3, s. 197-207
-
Tidskriftsartikel (refereegranskat)abstract
- The main purpose of the study was to investigate Hypothalamic-Pituitary-Adrenal (HPA) axis characteristics in relation to suicidal intent among suicide attempters with Major Depressive Disorder (MDD) and Adjustment Disorders (AD). The relationship between suicidal intent, assessed by means of the Suicidal Intent Scale (SIS), and serum cortisol after a Dexamethasone Suppression Test (DST) was investigated in 78 suicide attempters, divided into diagnostic subgroups. There was a significant negative correlation between suicidal intent and post DST cortisol in patients with MDD. Our findings may be attributed to pathophysiological processes, where a high suicidal intent is revealed during a potential chronic course of MDD, which in turnresults in a seemingly normal stress system.
|
|
| 10. |
- Suneson, Klara, et al.
(författare)
-
Low total cholesterol and low-density lipoprotein associated with aggression and hostility in recent suicide attempters
- 2019
-
Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781. ; 273, s. 430-434
-
Tidskriftsartikel (refereegranskat)abstract
- Low cholesterol levels have been correlated with both suicidal and aggressive behavior in psychiatric patients. Few studies have investigated associations between serum lipid profiles and both aggressive state and trait. Fifty-two psychiatric medication-free inpatients were included in this study after a suicide attempt. Composite scores of “State Aggression” and “Trait Aggression” were calculated using relevant items from the Comprehensive Psychopathological Rating Scale and the Karolinska Scales of Personality. State Aggression was significantly and negatively correlated with total cholesterol (TC) and low-density lipoprotein (LDL). Trait Aggression was also significantly and negatively correlated with LDL, but not TC. There were small but significant mediation effects of severity of anxiety symptoms on the relationship between State Aggression and TC as well as LDL. In exploratory analyses we found that low cholesterol was also associated with personality traits of hostility. Moreover, low cholesterol was more robustly associated with personality trait items related to interpersonal aggression, as opposed to items related to irritability or more indirect, non-overt aggression. Our findings suggest that low cholesterol is associated with both state and trait aggression in suicide attempters. Future mechanistic studies are warranted to better understand the relationship between low cholesterol and high aggression in suicide attempters.
|
|
