Low total cholesterol and low-density lipoprotein associated with aggression and hostility in recent suicide attempters.

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.

Six autoantibodies associated with autoimmune encephalitis are not detectable in the cerebrospinal fluid of suicide attempters.

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.

A systematic review including meta-analysis of work environment and burnout symptoms.

BACKGROUND: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies - original as well as reviews - restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms. METHODS: A wide range of work exposure factors was screened. Inclusion criteria were: 1) Study performed in Europe, North America, Australia and New Zealand 1990-2013. 2) Prospective or comparable case control design. 3) Assessments of exposure (work) and outcome at baseline and at least once again during follow up 1-5 years later. Twenty-five articles met the predefined relevance and quality criteria. The GRADE-system with its 4-grade evidence scale was used. RESULTS: Most of the 25 studies focused emotional exhaustion, fewer cynicism and still fewer personal accomplishment. Moderately strong evidence (grade 3) was concluded for the association between job control and reduced emotional exhaustion and between low workplace support and increased emotional exhaustion. Limited evidence (grade 2) was found for the associations between workplace justice, demands, high work load, low reward, low supervisor support, low co-worker support, job insecurity and change in emotional exhaustion. Cynicism was associated with most of these work factors. Reduced personal accomplishment was only associated with low reward. There were few prospective studies with sufficient quality on adverse chemical, biological and physical factors and burnout. CONCLUSION: While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion. Our approach with a wide range of work exposure factors analysed in relation to the separate dimensions of burnout expanded the knowledge of associations, evidence as well as research needs. The potential of organizational interventions is illustrated by the findings that burnout symptoms are strongly influenced by structural factors such as job demands, support and the possibility to exert control.

Plasma Brain-Derived Neurotrophic Factor and Psychopathology in Attempted Suicide.

BACKGROUND/AIMS: Increasing evidence suggests a link between brain-derived neurotrophic factor (BDNF) and suicidal behaviour (SB). Furthermore, decreased peripheral BDNF levels have been associated with clinical symptoms in various psychiatric disorders as well as with personality dimensions in healthy individuals. However, the relationship between BDNF and psychopathology is poorly investigated regarding SB. METHODS: Plasma BDNF concentrations were analysed in 61 recent suicide attempters. Clinical symptoms were evaluated using the Comprehensive Psychopathological Rating Scale. Personality dimensions were assessed using the Marke-Nyman Temperament Scale. RESULTS: Plasma BDNF correlated positively and significantly with the personality dimension Solidity but not with the other personality dimensions or with clinical symptoms. CONCLUSION: BDNF plays an important role in the regulation of neuroplasticity and neurogenesis in humans. Our results indicate that lower BDNF concentrations are associated with higher levels of impulsiveness and changeability (low scores on the Solidity scale). Furthermore, low plasma BDNF levels may be proposed as a trait marker rather than a state marker for attempted suicide.

Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters.

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.

Increased Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in Plasma of Suicide Attempters.

The soluble form of the urokinase receptor, suPAR, has been suggested as a novel biomarker of low-grade inflammation. Activation of the immune system has been proposed to contribute to the development of depression and suicidal behavior. In order to identify depressed and suicidal individuals who could benefit from an anti-inflammatory treatment, a reliable biomarker of low-grade inflammation is vital. This study evaluates plasma suPAR levels as a biomarker of low-grade inflammation in patients with major depressive disorder and in patients who recently attempted suicide. The plasma suPAR and an established biomarker, C reactive protein (CRP) of suicide attempters (n = 54), depressed patients (n = 19) and healthy controls (n = 19) was analyzed with enzyme-linked immunosorbent assays. The biomarker attributes of sensitivity and sensibility were evaluated using ROC curve analysis. Both the depressed patients and suicide attempters had increased plasma suPAR. The levels of suPAR discriminated better between controls and suicide attempters than did CRP. In the future, plasma suPAR might be a superior prognosticator regarding outcome of treatment applying conventional antidepressants in conjunction with anti-inflammatory drugs.

A systematic review including meta-analysis of work environment and depressive symptoms.

BACKGROUND: Depressive symptoms are potential outcomes of poorly functioning work environments. Such symptoms are frequent and cause considerable suffering for the employees as well as financial loss for the employers. Accordingly good prospective studies of psychosocial working conditions and depressive symptoms are valuable. Scientific reviews of such studies have pointed at methodological difficulties but still established a few job risk factors. Those reviews were published some years ago. There is need for an updated systematic review using the GRADE system. In addition, gender related questions have been insufficiently reviewed. METHOD: Inclusion criteria for the studies published 1990 to June 2013: 1. European and English speaking countries. 2. Quantified results describing the relationship between exposure (psychosocial or physical/chemical) and outcome (standardized questionnaire assessment of depressive symptoms or interview-based clinical depression). 3. Prospective or comparable case-control design with at least 100 participants. 4. Assessments of exposure (working conditions) and outcome at baseline and outcome (depressive symptoms) once again after follow-up 1-5 years later. 5. Adjustment for age and adjustment or stratification for gender. Studies filling inclusion criteria were subjected to assessment of 1.) relevance and 2.) quality using predefined criteria. Systematic review of the evidence was made using the GRADE system. When applicable, meta-analysis of the magnitude of associations was made. Consistency of findings was examined for a number of possible confounders and publication bias was discussed. RESULTS: Fifty-nine articles of high or medium high scientific quality were included. Moderately strong evidence (grade three out of four) was found for job strain (high psychological demands and low decision latitude), low decision latitude and bullying having significant impact on development of depressive symptoms. Limited evidence (grade two) was shown for psychological demands, effort reward imbalance, low support, unfavorable social climate, lack of work justice, conflicts, limited skill discretion, job insecurity and long working hours. There was no differential gender effect of adverse job conditions on depressive symptoms CONCLUSION: There is substantial empirical evidence that employees, both men and women, who report lack of decision latitude, job strain and bullying, will experience increasing depressive symptoms over time. These conditions are amenable to organizational interventions.

A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality.

BACKGROUND: Patients with depression and suicidality suffer from low-grade neuroinflammation. Pro-inflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-d-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF). METHODS: We measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n=143, individuals n=30) and healthy controls (n=36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Asberg Depression Rating Scale and the Suicide Assessment Scale. RESULTS: Quinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms. CONCLUSIONS: We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression.

Associations between avoidant focused coping strategies and polymorphisms in genes coding for brain-derived neurotrophic factor and vascular endothelial growth factor in suicide attempters: a preliminary study.

In this study we investigated whether single nucleotide polymorphisms (SNP) in the genes coding for BDNF (Val66Met) and VEGF (C2578A) may be associated with maladaptive strategies among suicide attempt patients. We found that BDNF Val66Met gene polymorphism probably affect avoidant coping strategies.

Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the DAOA and COMT genes.

INTRODUCTION: Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function. METHODOLOGY: Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text]. RESULTS: The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text]. CONCLUSION: Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population.

Connecting inflammation with glutamate agonism in suicidality.

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 (P<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.

The +1444C>T polymorphism in the CRP gene: a study on personality traits and suicidal behaviour.

OBJECTIVES: Numerous studies have shown associations between an on-going depression and elevated serum levels of the acute-phase reactant C-reactive protein (CRP). Also, in suicidal behaviour, a proinflammatory state has been suggested to be of importance for the pathophysiology. There is a genetic susceptibility to suicidal behaviour, but studies with respect to genes related to inflammation are sparse. We have previously reported an association between a polymorphism located in the CRP gene, +1444C>T (rs1130864), and the personality trait impulsiveness in women assessed using the Karolinska Scales of Personality. The present study aims to replicate these results in suicide attempters and examine whether the polymorphism is associated with suicidal behaviour. MATERIALS AND METHODS: The +1444C>T polymorphism was genotyped in suicide attempters from two cohorts (a total of 106 patients) and healthy controls (n=517). RESULTS: We could replicate our previous finding, as the +1444T allele was associated with higher scores in the Karolinska Scales of Personality factor extraversion and its subscale impulsiveness in one of the patient cohorts. Furthermore, the +1444T allele was significantly more common among suicide attempters compared with the +1444C allele. CONCLUSION: The present results lend further support to the relevance of inflammation for suicidal behaviour. The association between the polymorphism and personality trait impulsiveness reinforces our hypothesis of the importance of immune-related genes also for normal mental functions such as personality traits. Given the fact that impulsiveness is a well-known risk factor for suicidal behaviour, we further hypothesize that the polymorphism studied may in part explain this relationship.

Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters.

Chemokines constitute a class of small inflammatory proteins that control the chemotaxis of leukocytes. They are also present in the central nervous system (CNS) and contribute to diverse physiological functions, such as the regulation of cell migration, axonal growth and neuronal survival. It is to date not known whether chemokines in the CNS are affected in psychiatric disorders. In this study, chemokine levels were measured in the cerebrospinal fluid (CSF) of 137 psychiatric patients in conjunction to a suicide attempt, and 43 healthy controls. A subgroup of patients (n = 42) was followed up with blood samples 12 years after the initial CSF collection, when they did not show suicidal behavior. The follow-up chemokine levels were compared to those of psychiatric patients (n = 17) who had never attempted suicide. Ultra-sensitive chemokine multiplex immunoassay was used to quantify eotaxin-1 (CCL11), interferon gamma-induced protein-10 (IP-10, CXCL10), macrophage inflammatory protein-1ß (MIP-1ß, CCL4), monocyte chemotactic protein-1 (MCP-1, CCL2), MCP-4 (CCL13) and thymus and activation regulated chemokine (TARC, CCL17). Patients were diagnosed using DSM-III-R/DSM-IV, and assessed using the Comprehensive Psychopathological Rating Scale (CPRS), including subscales, and the Suicidal Intent Scale (SIS). CSF eotaxin-1, MIP-1ß, MCP-1, MCP-4 and TARC were significantly lower in suicide attempters than in healthy controls. Low chemokine levels were specifically associated with psychotic symptoms and pain. In the samples collected at follow-up, TARC was significantly lower in suicide attempters compared to psychiatric patients who had never attempted suicide. We also found a positive correlation between blood TARC and brain-derived neurotrophic factor (BDNF) levels. Our study thus provides evidence of reduced chemokine levels in suicide attempters, both in the acute suicidal setting, and at long-term, compared to non-attempters. These results warrant future studies on the detailed neurobiological functions of chemokines in psychiatric patients.

Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence.

OBJECTIVE: The primary aim was to relate Toxoplasma gondii seropositivity and serointensity to scores on the self-rated Suicide Assessment Scale (SUAS-S). Another aim was to reevaluate the previously reported positive association between T gondii serointensity and a history of nonfatal suicidal self-directed violence. METHOD: This cross-sectional, observational study compared T gondii serointensity and seropositivity in plasma from 54 adult suicide attempters (inpatients at Lund University Hospital, Lund, Sweden) and 30 adult control subjects (randomly selected from the municipal population register in Lund, Sweden) recruited between 2006 and 2010. The potential of patients and controls for self-directed violence was evaluated with the SUAS-S. Psychiatric diagnoses were made according to DSM-IV criteria. Plasma samples were tested for immunoglobulin G antibodies to T gondii, cytomegalovirus, and herpes simplex virus type 1. Data were analyzed using multivariable logistic regression to investigate the association between T gondii serointensity or seropositivity and a history of nonfatal suicidal self-directed violence; multivariable linear regression was used to explore the relationship between T gondii serointensity or seropositivity and the SUAS-S. Both regression models included sex, age, and body mass index as covariates. RESULTS: Seropositivity of T gondii (adjusted odds ratio [OR] = 7.12; 95% CI, 1.66-30.6; P = .008) and serointensity of T gondii (adjusted OR = 2.01; 95% CI, 1.09-3.71; P = .03) were positively associated with a history of nonfatal suicidal self-directed violence. Seropositivity of T gondii was associated with higher SUAS-S scores, a relationship significant for the whole sample (P = .026), but not for suicide attempters only. No significant associations with other pathogens were identified. CONCLUSIONS: These results are consistent with previous reports on the association between T gondii infection and nonfatal suicidal self-directed violence. Confirming these results in future large longitudinal studies and including suicide as an outcome may lead to novel individualized approaches in suicide prevention.

P2RX7: expression responds to sleep deprivation and associates with rapid cycling in bipolar disorder type 1.

CONTEXT: Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatment-responsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling. OBJECTIVES: To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients. DESIGN: Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients. PARTICIPANTS: Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044). RESULTS: P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10(-9)). The P2RX7 rs2230912 _A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls. CONCLUSIONS: Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system.

Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.

OBJECTIVE: Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene. METHODS: Key symptoms of mania were rated in two sets of medicated bipolar disorder patients (n=171 and n=475) at two specialized outpatient clinics for affective disorders and three regular psychiatric outpatient units in Sweden. The relationships between all manic symptoms according to DSM-IV were entered in a principal component analysis. We used a case-case model to reduce the genetic heterogeneity and tested associations between four factors related to manic symptoms and their association to four single nucleotide polymorphisms in the P2RX7 gene. RESULTS: The combination of the cognitive symptoms, distractibility, talkativeness, and thought disorder was significantly associated with rs1718119 in the P2RX7 gene in Set 1 [odds ratio (OR) = 1.78; p=0.011]. The association was re-tested in the second set (OR = 1.42; p=0.009). In the total sample, the association was even stronger (OR = 1.49; p<0.001). None of the other factors was associated with the P2RX7 gene. Within the first factor, the distractibility symptom accounted for a significant portion of the association to rs1718119 (p=0.016). CONCLUSION: There is an association between specific symptoms of bipolar disorder and the P2RX7 gene. This finding may open up new approaches to elucidating the neurobiology behind bipolar symptoms.

Cytokine levels in the blood may distinguish suicide attempters from depressed patients.

Elevated plasma cytokines is a common finding in Major Depressive Disorder (MDD), although not consistent. It is currently not known whether the inflammatory changes are confined to any specific subgroup of depressive patients. We here analyzed three inflammatory markers in suicidal and non-suicidal depressed patients, as well as healthy controls. Plasma interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-α were measured in 47 suicide attempters, 17 non-suicidal depressed patients and 16 healthy controls. Study participants were evaluated using the Comprehensive Psychopathological Rating Scale (CPRS) with subscales for anxiety and degree of depression, as well as the Suicide Assessment Scale (SUAS). We found increased levels of IL-6 and TNF-α as well as decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and healthy controls. The results were adjusted for potential confounders of cytokine expression, such as age, sex, body mass index (BMI), degree of depression, anxiety, personality disturbance, abuse and type of medication. These results demonstrate for the first time that suicidal patients display a distinct peripheral blood cytokine profile compared to non-suicidal depressed patients. Thus, our study provides further support for a role of inflammation in the pathophysiology of suicidality.

Decreased aldosterone in the plasma of suicide attempters with major depressive disorder.

Hormones and neurobiological factors may be regulated differently in suicidal versus non-suicidal depressive patients. There is currently limited knowledge about the relation of substances in the Renin-Angiotensin-Aldosterone system to depression and suicidality. We therefore investigated whether plasma levels of renin and aldosterone differ between suicide attempters, non-suicidal depressive patients and healthy controls. Furthermore, we analyzed the relation of renin and aldosterone to psychiatric symptoms in the patients. Suicidal patients with MDD, adjustment disorder and dysthymia, as well as two control groups consisting of non-suicidal MDD patients and healthy subjects, were rated using the Comprehensive Psychopathological Rating Scale (CPRS), including the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Plasma samples were frozen immediately after collection and stored at -80°C for 5-18years. Aldosterone and renin levels were analyzed using radioactive- and chemiluminescent immunoassays. We found that suicide attempters with MDD had significantly lower plasma levels of aldosterone than the other patient groups, as well as than the healthy controls. Moreover, increasing severity of psychiatric symptoms was associated with lower aldosterone levels in the suicide attempters with MDD. Non-suicidal patients with MDD did not differ significantly compared to healthy controls with respect to aldosterone and renin levels. These findings may indicate that low aldosterone levels could be a marker of suicidality in patients with MDD.