Six Major Steps to Make Investigations of Suicide Valuable for Learning and Prevention.

OBJECTIVE: The decline in suicide rates has leveled off in many countries during the last decade, suggesting that new interventions are needed in the work with suicide prevention. Learnings from investigations of suicide should contribute to the development of these new interventions. However, reviews of investigations have indicated that few new lessons have been learned. To be an effective tool, revisions of the current investigation methods are required. This review aimed to describe the problems with the current approaches to investigations of suicide as patient harm and to propose ways to move forward. METHODS: Narrative literature review. RESULTS: Several weaknesses in the current approaches to investigations were identified. These include failures in embracing patient and system perspectives, not addressing relevant factors, and insufficient competence of the investigation teams. Investigation methods need to encompass the progress of knowledge about suicidal behavior, suicide prevention, and patient safety. CONCLUSIONS: There is a need for a paradigm shift in the approaches to investigations of suicide as potential patient harm to enable learning and insights valuable for healthcare improvement. Actions to support this paradigm shift include involvement of patients and families, education for investigators, multidisciplinary analysis teams with competence in and access to relevant parts across organizations, and triage of cases for extensive analyses. A new model for the investigation of suicide that support these actions should facilitate this paradigm shift.HIGHLIGHTSThere are weaknesses in the current approaches to investigations of suicide.A paradigm shift in investigations is needed to contribute to a better understanding of suicide.New knowledge of suicidal behavior, prevention, and patient safety must be applied.

25(OH)D levels are decreased in patients with difficult-to-treat depression.

Objectives: The 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. Method: We 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. Results: Patients 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). Limitations: The 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. Conclusion: The 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.

Executive functioning in psychiatric patients with deliberate self-harm, as compared with a psychiatric and a healthy comparison group.

Introduction: Deliberate self-harm (DSH) is a common symptom in psychiatric disorders. It is a cross-diagnostic symptom, although it has mainly been associated with borderline personality disorder (BPD). Research has suggested an association between DSH and deficits in executive functioning. The main aim of the current study was to assess three specific aspects of executive functioning (EF) (working memory, inhibition and cognitive flexibility) among psychiatric patients with DSH, compared to a clinical and a healthy comparison group.Methods: Thirty psychiatric patients with DSH, 29 psychiatric patients without DSH and 29 healthy individuals were assessed with regard to psychiatric illness, self-harming behavior, EF, general cognitive functioning level and measures of psychopathology. The results were analyzed by means of ANOVA, regression analysis, Chi-square, and correlation analysis.Results: The patients with DSH showed deficits in cognitive flexibility and inhibition as compared to healthy individuals. In addition, the patients with DSH had greater deficits in cognitive flexibility than the patients without DSH; this effect was independent of concurrent severity of depressive symptoms but not independent of borderline symptomatology.Conclusion: Psychiatric patients with DSH may have deficits in cognitive flexibility as compared to both the healthy and clinical comparison groups. The results partly differ from previous related studies in the field. It is unclear to which extent the deficits in cognitive flexibility are due to other factors. More research is needed to understand the implications of such deficits, and if the results could be used for adapting treatment services and strategies. Future studies should include more similar comparison groups.

Leaky gut biomarkers in depression and suicidal behavior.

OBJECTIVE: Inflammation is associated with major depressive disorder (MDD) and suicidal behavior. According to the 'leaky gut hypothesis', increased intestinal permeability may contribute to this relationship via bacterial translocation across enterocytes. We measured plasma levels of gut permeability markers, in patients with a recent suicide attempt (rSA), MDD subjects with no history of a suicide attempt (nsMDD), and healthy controls (HC), and related these markers to symptom severity and inflammation. METHOD: We enrolled rSA (n = 54), nsMDD (n = 13), and HC (n = 17). Zonulin, intestinal fatty acid binding protein (I-FABP), soluble CD14, and interleukin-6 (IL-6) were quantified in plasma. Montgomery-Åsberg Depression Rating Scale (MADRS) and Suicide Assessment Scale (SUAS) were used for symptom assessments. RESULTS: The rSA group displayed higher I-FABP and lower zonulin levels compared with both the nsMDD and the HC groups (all P < 0.001). IL-6 correlated positively with I-FABP (r = 0.24, P < 0.05) and negatively with zonulin (r = -0.25, P < 0.05). In all subjects, I-FABP levels correlated positively with MADRS (r = 0.25, P < 0.05) and SUAS scores (r = 0.38, P < 0.001), and the latter correlation was significant also in the nsMDD group (r = 0.60, P < 0.05). CONCLUSION: The 'leaky gut hypothesis' may improve our understanding of the link between inflammation and suicidal behavior. These findings should be considered preliminary until replicated in larger cohorts.

Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity.

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.

Low IL-8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels.

OBJECTIVE: Recent studies indicate that inflammation may play a role in the pathophysiology of suicidality. Interleukin-8 (IL-8) is a chemokine that in addition to its function in the immune system also exert neuroprotective properties. The involvement of this chemokine in neuropsychiatric conditions is incompletely known. METHOD: We measured plasma and cerebrospinal fluid (CSF) IL-8, as well as the genotype frequency of a single nucleotide polymorphism (-251A/T, rs4073) in the promoter region of the IL8 gene, in suicide attempters (n=206) and healthy controls (n=578). RESULTS: Plasma and CSF levels of IL-8 were significantly lower in suicide attempters with anxiety than in healthy controls. IL-8 in both plasma and CSF correlated negatively with symptoms of anxiety. Compared with the population-based cohort, the IL-8-251T allele was more prevalent among female suicide attempters. Furthermore, suicide attempters carrying this allele showed more severe anxiety. This correlative study warrants further mechanistic studies on the effects of IL-8 in the central nervous system. CONCLUSION: We suggest that IL-8 might be involved in the biological mechanisms mediating resilience to anxiety. Thus, our findings highlight the chemokine IL-8 as a potential target for future development of anti-anxiety treatments and suicide prevention.

Grasping the dynamics of suicidal behaviour: combining time-geographic life charting and COPE ratings.

ACCESSIBLE SUMMARY: • A primary aim of suicide research is to gain a profound knowledge of the suicidal individual so preventive strategy can be formulated. • Time-geographic life charting used in combination with the pattern of coping strategies may be helpful when assessing risk of suicidal behaviour. • It can also be a therapeutic intervention to look back and to reflect coping styles. ABSTRACT: The aim of this study is to explore whether a time-geographic life charting, combined with a survey of a person's coping capacities over time, elucidates the pathway to suicidal behaviour, and therefore could be useful in suicide prevention. Twenty-three patients were recruited shortly after a suicide attempt. A time-geographic life charting and COPE inventory ratings were used separately and in combination. According to COPE ratings, the participants could be divided into three groups using different coping strategies: (1) adaptive, (2) maladaptive, and (3) both adaptive and maladaptive coping. Within these subgroups, three different pathways to suicidal behaviour were described and illustrated. We conclude that time-geographic life charting used in combination with the pattern of coping strategies may be helpful when assessing risk of suicidal behaviour, because this approach strengthens the comprehensive picture of the patient's life situation.

A follow up study of suicide attempters: increase of CSF-somatostatin but no change in CSF-CRH.

Concentrations of somatostatin and corticotrophin releasing hormone (CRH), measured in cerebrospinal fluid (CSF) have been reported to be low in suicidal patients with major depressive disorder (MDD). Often have MDD patients in general, high CSF-CRH and low CSF-somatostatin concentrations, which both seem to normalise with clinical recovery. The present study was designed to look for CSF-CRH and CSF-somatostatin alterations along with clinical changes in patients studied repeatedly after a suicide attempt. Sixteen patients with different diagnoses, initially inpatients after a suicide attempt (baseline), participated. Lumbar punctures and ratings according to the Suicidal Assessment Scale (SUAS) and the Montgomery-Asberg Depression Rating Scale (MADRS) were performed while patients were drug-free (baseline) and after a median of 7 (5 to 9) months. At follow up MADRS- and SUAS-scores were significantly decreased (P<0.05), whereas CSF-somatostatin was significantly increased (P=0.013) and CSF-CRH had not changed significantly. Thus, the patients showed long-lasting low CSF-CRH concentrations, in spite of changed CSF-somatostatin concentrations and clinical amelioration.

Stress system alterations and mood disorders in suicidal patients. A review.

Stress system alterations, in particular HPA axis hyperactivations, are fairly well documented in suicide victims and in depressed suicide attempters who subsequently complete suicide. In suicide attempters with no documented completed suicide, the results are more inconsistent. This may depend on differences in studies due to diagnostic heterogeneity among suicide attempters, and the time between the suicide attempt and the examination. Recent data suggests differences in the stress system between depressed patients with a recent suicide attempt and depressed patients in general. The field merits further examination, with thorough examinations of genotypes, actual suicide attempts and stress in combination with examinations of the stress system.

Temperament traits in seasonal affective disorder, suicide attempters with non-seasonal major depression and healthy controls.

BACKGROUND: Very few studies have compared the temperament traits in matched suicidal and non-suicidal patients with major depression. METHODS: We compared the temperament traits in two matched groups of patients with major depressive disorder (MDD), MDD with seasonal subtype (SAD) without any suicide attempt (n = 23) and MDD without seasonal variation who attempted suicide (non-SAD SA), and compared the patients to matched healthy controls by using the Karolinska Scales of Personality (KSP) and the Marke-Nyman Temperament (MNT) questionnaires. RESULTS: Both the SAD and non-SAD SA groups showed significantly higher Somatic Anxiety, Muscular Tension, Psychasthenia, Irritability, Suspicion, and lower Socialization and Validity than the controls. The non-SAD SA group also showed significantly higher Psychic Anxiety, Detachment and Guilt as compared to controls. When the SAD and the non-SAD SA were compared, we found significantly higher Somatic Anxiety, Psychic Anxiety and Muscular Tension for the non-SAD SA group. CONCLUSIONS: Both SAD and non-SAD SA patients display different temperament profiles compared to controls and in comparison with each other and the suicide attempters show especially high trait anxiety and hostility. CLINICAL RELEVANCE: The results suggest that trait anxiety and hostility, but not impulsivity, are associated with suicidal behavior in major depression.

Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recent suicide attempt.

In order to receive a further understanding of stress-regulation in depressed suicide attempters, peptides that are supposed to be related to the stress system (the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system) were studied in plasma. When compared with healthy controls, cortisol was high (p<0.001) and corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) appeared to be low (p<0.001) in patients who had recently attempted suicide. Patients who had repeatedly attempted suicide had the lowest NPY. A correlation between NPY and cortisol (p<0.05) was found in suicidal patients with depression NOS, whereas beta-endorphins correlated with cortisol (p<0.01) in suicidal patients with major depressive disorder. A postdexamethasone decrease of NPY was noted in the controls but not in the patients. These results suggest stress system alterations in suicidal patients with mood disorders.

High delta sleep-inducing peptide-like immunoreactivity in plasma in suicidal patients with major depressive disorder.

BACKGROUND: Delta sleep-inducing peptide (DSIP) supposedly involves the hypothalamus-pituitary-adrenal (HPA) axis. Previous studies have shown deviated plasma DSIP-like immunoreactivity (DSIP-LI) levels, as well as abnormal DSIP-LI responses to corticotropin-releasing hormone in patients with major depressive disorder (MDD). This study was performed to investigate plasma-DSIP-LI and its association with the dexamethasone suppression test (DST) in suicide attempters. METHODS: Plasma-DSIP and serum cortisol were measured before and after dexamethasone intake in 34 suicide attempters and in healthy age- and sex-matched controls. RESULTS: We found significantly elevated DSIP-LI levels in MDD patients (p < .005), and a significant correlation between predexamethasone cortisol and predexamethasone DSIP-LI levels in healthy controls. Postdexamethasone DSIP-LI levels increased in subjects with low predexamethasone DSIP-LI levels, whereas they decreased in subjects with high predexamethasone DSIP-LI levels. CONCLUSIONS: Results give some support to the theory of glucocorticoid involvement in the regulation of DSIP, and suggest altered DSIP-LI levels in suicidal MDD patients.

Correlations between plasma-neuropeptides and temperament dimensions differ between suicidal patients and healthy controls.

BACKGROUND: Decreased plasma levels of plasma-neuropeptide Y (NPY) and plasma-corticotropin releasing hormone (CRH), and increased levels of plasma delta-sleep inducing peptide (DSIP) in suicide attempters with mood disorders have previously been observed. This study was performed in order to further understand the clinical relevance of these findings. METHODS: Examination of correlates between temperament dimensions (Karolinska Scales of Personality (KSP), the Eysenck Personality Questionnaire together with the IVE- impulsiveness scale (EPQI), and the Marke-Nyman Temperament (MNT)) and NPY, CRH and DSIP and serum-cortisol in the dexamethasone suppression test (DST) in 38 suicidal patients and matched controls. RESULTS: NPY correlated significantly and positively with psychasthenia, irritability, and stability and significantly and negatively with validity in patients, but significantly and negatively with muscular tension, psychasthenia, verbal aggression and irritability in controls. DSIP correlated significantly and positively with impulsiveness (EPQI) in controls. CRH correlated negatively with lie in controls. Cortisol correlated significantly and positively with validity, extraversion and verbal aggression and significantly and negatively with inhibition of aggression in controls. CONCLUSION: NPY may be related to stress tolerance. DSIP seems to be associated with impulsivity/antisocial traits. LIMITATIONS: Non-suicidal patients were not included in the examination. CLINICAL RELEVANCE: The state of depression or stress seems to influence the correlations studied.