Cerebrospinal fluid monoamine metabolites and suicide

Prospective studies of the serotonergic system and suicide report that low 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and a history of attempted suicide predict suicide risk. Low CSF homovanillic acid (HVA) is reported to be associated with past and future lethality of suicide attempts but not with suicide. The interrelationships between monoamine metabolites, violent method, suicide intent and lethality of suicidal behaviour are complex. We hypothesized that CSF 5-HIAA and HVA levels are related to suicide intent, violence and lethality of suicidal behaviour. Fifteen male suicide attempters admitted to a psychiatric ward at the Karolinska University Hospital and eight healthy male volunteers were submitted to lumbar puncture and CSF 5-HIAA and HVA were assayed. Suicide intent with the Beck Suicide Intent Scale (SIS), lethality and violence of suicidal behaviour were assessed. All patients were followed up for causes of death. Six suicides and one fatal accident were identified with death certificates. Mean CSF 5-HIAA but not CSF HVA differed between suicides and survivors. Violent suicides had higher suicide intent and CSF 5-HIAA than non-violent suicides. In violent suicides, CSF 5-HIAA levels were negatively correlated with SIS. Greater suicide intent may be associated with greater aggressive intent and predicts a violent suicide method.     

CSF 5-HIAA, suicide intent and hopelessness in the prediction of early suicide in male high-risk suicide attempters

OBJECTIVE: To study the predictive value of the Beck Suicide Intent Scale (SIS), the Beck Hopelessness Scale (BHS) and of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid for future early suicide in a group of high-risk male suicide attempters. METHOD: Fifteen consecutive male suicide attempters admitted to a psychiatric ward at the Karolinska Hospital, who were not receiving any treatment with antidepressants were diagnosed according to DSM-III, assessed with SIS and BHS and submitted to lumbar puncture. All patients were followed up for cause of death. RESULTS: Five early suicides (within 2 years) were identified. Mean cerebrospinal fluid (CSF) 5-HIAA differed between suicides and survivors. Low CSF 5-HIAA was identified in those who committed early suicide. Neither the Suicide Intent Score nor the Hopelessness Score distinguished suicides from survivors. CONCLUSION: In high suicide risk hospitalized male psychiatric patients CSF 5-HIAA may be a better predictor of early suicide after attempted suicide than SIS or BHS.     

Low CSF oxytocin reflects high intent in suicide attempters

Data from animal studies suggest that oxytocin is an important modulating neuropeptide in regulation of social interaction. One human study has reported a negative correlation between CSF oxytocin levels, life history of aggression and suicidal behaviour. We hypothesized that CSF oxytocin levels would be related to suicidal behaviour, suicide intent, lifetime interpersonal violence and suicide risk. 28 medication free suicide attempters and 19 healthy volunteers participated in this cross sectional and longitudinal study. CSF and plasma morning basal levels of oxytocin were assessed with specific radio-immunoassays. The Beck Suicide Intent Scale (SIS), the Freeman scale and the Karolinska Interpersonal Violence Scale (KIVS) were used to assess suicide intent and lifetime violent behaviour. All patients were followed up for cause of death. The mean follow-up was 21 years. Suicide attempters had lower CSF oxytocin levels compared to healthy volunteers p=0.077. In suicide attempters CSF oxytocin showed a significant negative correlation with the planning subscale of SIS. CSF oxytocin showed a significant negative correlation with suicide intent, the planning subscale of SIS and Freeman interruption probability in male suicide attempters. Correlations between plasma oxytocin levels and the planning subscale of SIS and Freeman interruption probability were significant in male suicide attempters. Lifetime violent behaviour showed a trend to negative correlation with CSF oxytocin. In the regression analysis suicide intent remained a significant predictor of CSF oxytocin corrected for age and gender whereas lifetime violent behaviour showed a trend to be a predictor of CSF oxytocin. Oxytocin levels did not differ significantly in suicide victims compared to survivors. CSF oxytocin may be an important modulator of suicide intent and interpersonal violence in suicide attempters.     

Hopelessness,impulsiveness and intent among suicide attempters with major depression,alcohol dependence,or both

The present study examined differences in hopelessness, impulsiveness and suicide intent between suicide attempters with either major depression or alcohol dependence, comorbid major depression and alcohol dependence, and those without these disorders. A sample of 114 patients from consecutive cases of attempted suicide referred to a general hospital in Helsinki was interviewed and diagnosed according to DSM-III-R. Suicide intent was measured by the Beck Suicide Intent Scale (SIS) and hopelessness was assessed by the Beck Hopelessness Scale (HS). Impulsiveness of the suicide attempt was measured by two items of the SIS. Suicide attempters with major depression without comorbid alcohol dependence had higher suicide intent and lower impulsiveness than attempters with non-depressive alcohol dependence. Suicide attempts may differ between subjects with major depression, alcoholism or both disorders in terms of impulsiveness and suicide intent.     

The dexamethasone suppression test and CSF-5-HIAA in relation to suicidality and depression in suicide attempters.

This study tested suicidality in relation to cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and the dexamethasone suppression test. Patients with nonsuppression of cortisol had the highest scores of the Suicide Assessment Scale (SUAS) and the Montgomery Asberg Depression Rating Scale (MADRS), respectively (P < 0.05; P < 0.01). The results persisted when analysed for covariance with CSF-5-HIAA. We have previously noted an elevated suicide risk in suicide attempters with high SUAS-scores, why a large part of nonsuppressors may be at high risk for future suicide.     

Clinical correlates of intent in attempted suicide.

The seriousness of suicide attempts was evaluated in 62 consecutive referrals in 2 general hospitals. As measured by the Suicide Intent Scale (SIS) the majority of cases had a low to moderate intention to die. Increasing age, psychosis and deliberate self-injury were associated with high suicidal intent. Hopelessness and a sense of isolation are significantly more frequent antecedent ideo-affective states in cases with high intent and anger and frustration are more prevalent in cases with low intent. Two other measures of seriousness, the medical condition on admission and lethality of the method used, correlate significantly with the degree of intent. The SIS can distinguish between relatively homogeneous subgroups of suicide attempters for depth studies of aetiology and management.     

Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels.

BACKGROUND: We have proposed a stress-diathesis model for suicidal behavior, in which major depression is a stressor and the diathesis is shared with aggression. Neurotransmitter correlates of the stress or diathesis have not been adequately evaluated by previous studies, because they did not simultaneously examine the relationship of multiple neurotransmitters to all three psychopathologies in the same population. In the present study we investigated the relationship of monoamine metabolites to aggressivity, suicidal behavior, and depression in patients with mood disorders. METHODS: Ninety-three drug-free subjects with a major depressive episode underwent lumbar puncture and psychiatric evaluation. Cerebrospinal fluid CSF levels of 5hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA) and methoxy-hydroxy-phenylglycol (MHPG) were assayed. The relationships between monoamine metabolites and clinical variables were statistically evaluated. RESULTS: Higher lifetime aggressivity correlated significantly with lower CSF 5-HIAA. Lower CSF 5-HIAA and greater suicidal intent were found in high-lethality suicide attempters compared with low-lethality suicide attempters. Low-lethality attempters did not differ biologically from nonattempters. No correlation between CSF HVA and any of the psychopathological variables was found. Only aggression showed a trend statistically in correlating positively with CSF MHPG levels. CONCLUSIONS: Lower CSF 5-HIAA concentration was independently associated with severity of lifetime aggressivity and a history of a higher lethality suicide attempt and may be part of the diathesis for these behaviors. The dopamine and norepinephrine systems do not appear to be as significantly involved in suicidal acts, aggression, or depression. The biological correlates of suicide intent warrant further study.     

CSF 5-HIAA levels are lower in impulsive as compared to nonimpulsive violent suicide attempters and control subjects.

BACKGROUND: We studied CSF 5-HIAA and HVA concentrations in violent suicide attempters and examined their relationship with depression, anxiety, and impulsivity. METHODS: CSF 5-HIAA and HVA concentrations were determined very shortly after hospital admission and compared to those of a matched control population. Clinical evaluation was performed concomitantly; the level impulsivity was evaluated by the Impulsivity Rating Scale (IRS). RESULTS: Twenty-three patients and 23 control subjects were included. According to the IRS, 14 patients were classified as impulsive, including all patients suffering from personality disorders, and 9 as nonimpulsive, with a main DSM-IIIR diagnosis of melancholia. CSF 5-HIAA concentrations in the suicide group were significantly lower than in control subjects. This difference was entirely due to the impulsive suicide attempters. There was an inverse correlation between the IRS score and CSF 5-HIAA (r = -.47, p = .02) and only a trend for HVA (r = -.41, p = .078) levels in the suicide group. CONCLUSIONS: This study of a group of violent suicide attempters distinguished a subgroup of patients diagnosed with personality disorder with high impulsivity scores and a subgroup of patients with the main diagnosis of severe depression. CSF 5-HIAA was significantly lower in impulsive violent attempters than in nonimpulsive violent attempters, therefore desintangling violence from impulsivity and linking this biologic abnormality to impulsivity.     

Biogenic amine turnover and serum cholesterol in suicide attempt

The investigation of biological correlates of suicidal behavior is important in searching for possible changes in neuronal systems activity related to that behavior, so that pharmacological interventions may be proposed, especially in high-risk subjects. In a sample of 111 subjects admitted in a general hospital after suicide attempt, we studied the turnover of neurotransmitters by measuring the urinary output of the main metabolites of serotonin, dopamine and noradrenaline (5-HIAA, HVA, MHPG respectively), as well as serum cholesterol, and compared them to those of a group of 62 healthy controls. Venous blood samples and urine samples were collected within 24 hours of admission. Psychiatric diagnosis was made according to DSM-IIIR criteria and assessment of suicide intent with Beck's Suicidal Intent Scale (SIS). Fifty-four (54) subjects received the diagnosis of adjustment disorder, 25 of depression, 16 of schizophrenia and 16 of personality disorder. Fourteen subjects (14) had employed a violent mode of attempt. Urinary MHPG was found significantly higher in all diagnostic groups compared to controls. No difference was found concerning the excretion of HVA and 5-HIAA. Serum total cholesterol was found significantly lower both in violent and non-violent attempters compared to controls after correcting for age. No difference in serum cholesterol or MHPG was found between violent and non-violent attempts. Serum cholesterol and MHPG correlated negatively, while the correlations between cholesterol and 5-HIAA or HVA were not significant. Our results confirm previous reports of lower serum cholesterol in attempted suicide. They are also indicative of an increased noradrenaline turnover in subjects who attempt suicide, at least within 24 hours after the attempt. Whether this activation precedes or follows the attempt because of the specific stress, can not be answered at present. Received: 30 January 2001 / Accepted: 19 December 2001     

Suicidal intent and psychiatric symptoms among inpatient suicide attempters

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.     

Amine metabolites, neuroendocrine findings, and personality dimensions as correlates of suicidal behavior

Levels of 5-hydroxyindoleactic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid (CSF) of 62 female inpatients with major depression (n = 19), schizophrenic disorder (n = 18), alcohol dependence (n = 13), and other disorders (n = 12). Nineteen patients had attempted suicide immediately before admission, and six had used violent methods. Fifty-three patients received a dexamethasone suppression test (DST) following lumbar puncture and all completed the Marke-Nyman Temperament Scale (Hungarian version) within 10 days. CSF 5-HIAA was significantly lower in patients who had made violent suicide attempts, but did not differ between suicide attempters who had taken drug overdoses and nonattempters. CSF HVA showed no significant differences. Dexamethasone nonsuppression occurred more frequently among attempters, but this difference did not reach statistical significance. Among the three personality dimensions of the Marke-Nyman Scale, validity was lower and stability higher in suicidal patients; both findings were more pronounced in the violent subgroup. CSF 5-HIAA and Marke-Nyman validity were inversely correlated to each other in all three subgroups, and violent attempters could be separated from the other two groups by their simultaneously low CSF 5-HIAA values and Marke-Nyman validity scores.     

抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

Attempted suicide in older depressed patients: effect of cognitive functioning.

The authors explored cognitive functioning and suicidal behavior in older depressed patients. Inpatients age 50 years or older (N=103) with major depression, 45 of whom had attempted suicide, were evaluated within 1 week of their hospital admission. Measures of suicidal behavior included suicide attempter status, the Suicide Intent Scale (SIS), ratings of method used (violent/nonviolent), and seriousness of injuries sustained (lethality). The Mini-Mental State Exam (MMSE) score measured cognitive impairment; covariates were age, gender, and living arrangement. The MMSE score was not associated with suicide attempter status, but for attempters, MMSE score showed a positive association with SIS score, but not method or lethality. Findings suggest that although cognitive disturbance may be associated with less-deliberate acts among older depressed suicide attempters, it does not appear to influence the potential lethality of their behavior.     

Suicidal intent and the HPA-axis characteristics of suicide attempters with major depressive disorder and adjustment disorders

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 turn results in a seemingly normal stress system.     

CSF biomarkers in suicide attempters--a principal component analysis

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.     

The correlates of planning in adolescent suicide attempts

Adolescent suicide attempts are often impulsive. It has been suggested that individuals who make nonimpulsive (premeditated) attempts have greater suicidal intent and are more hopeless than the impulsive attempters. Eighty-six adolescent suicide attempters were categorized according to the degree of premeditation of their attempt, as measured by two items of the Suicide Intent Scale. Sex, age, method of attempt, and the number of prior attempts were not useful discriminators between these groups. The nonimpulsive attempters were significantly more depressed and more hopeless than the impulsive attempters, as measured by several standardized scales. Measures of depression, hopelessness, and suicidal ideation were highly correlated in both groups. Anger turned inward and hopelessness were strongly correlated only in the premeditated group, suggesting that the nonimpulsive attempter's distress may bear a strong relationship to self anger.     

A history of major depressive disorder influences intent to die in violent suicide attempters

BACKGROUND: The inconsistency of the results obtained in biological studies of suicidal behavior may be due to the use of broad categories lacking validity. In previous genetic studies, in which we identified an association between a serotonin-related gene and violent suicide attempts, we suggested that a history of major depressive disorder (MDD) might influence this association. In this study, we aimed to clarify the relationships between the violence of suicide attempts, intent to die, and depression in a large sample of suicide attempters. METHOD: We investigated intent to die, according to history of violent suicide attempts and MDD, in 502 consecutively admitted suicide attempters. We characterized patients in terms of lifetime DSM-IV Axis I diagnoses, suicidal intent (Beck Suicide Intent Scale), and history of violent suicide attempts. RESULTS: Suicidal intent, for both the last suicide attempt before admission and the most lethal suicide attempt, was higher in those with history of MDD (p =.03 and p =.04, respectively) but was not affected by history of violent suicide attempt. In violent suicide attempters, suicidal intent was higher in patients with a history of MDD than in patients with no such history (p =.04 for last suicide attempt and p =.02 for most lethal attempt), whereas MDD had no effect on suicidal intent in nonviolent suicide attempters. CONCLUSION: Violent suicide attempters constitute a heterogeneous group in terms of suicidal intent. Our results suggest that biological and genetic studies should take into account the method used to attempt suicide, intent to die, and history of MDD.     

Subjective psychological well-being (WHO-5) in assessment of the severity of suicide attempt

An objective way to measure the severity of suicide attempt is to use different psychometric scales. Aspects of suicide risk like suicidal intent, depression, hopelessness and well-being can be assessed and different practical scales are in use to facilitate the risk assessment procedure. The aims of current study were: 1) to analyse the association between the severity of suicide attempt measured by suicidal intent scale and characteristics of emotional status of suicide attempters measured by depression, hopelessness and well-being scales in different gender and age groups; 2) to test the applicability of well-being measured by the World Health Organisation well-being index (WHO-5) in suicide risk assessment. The data on suicide attempters (n=469) was obtained in Estonia (Tallinn) by the WHO Suicide Prevention-Multisite Intervention Study on Suicidal Behaviours (SUPRE-MISS) methodology. Different psychometric scales were used to measure suicidal intent (Pierce Suicidal Intent Scale) and emotional status (Beck Depression Inventory for depression, Beck Hopelessness Scale for hopelessness, WHO-5 for well-being). All psychometric scales correlated well with each other (P<0.05). Low level of well-being associated with high level of suicidal intent, depression and hopelessness. Suicidal intent correlated the most strongly with well-being. Analysis by gender and age groups revealed also significant correlations with two exceptions only: correlation between suicidal intent and hopelessness did not reach the significant level in males and in older adults (40+). The WHO-5 well-being scale, which is a short and emotionally positively loaded instrument measuring protective factors, can be used in settings without psychological/psychiatric expertise in preliminary suicide risk assessment.     

Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression

Depressed patients who had attempted suicide (N = 19) had significantly lower CSF homovanillic acid (HVA) levels than patients who had not attempted suicide (N = 8) and control subjects (N = 41). Intergroup levels of 5-hydroxyindoleacetic acid (5-HIAA) were not significantly different. The ratio of CSF HVA to CSF 5-HIAA was significantly lower in both patient groups than in control subjects, and patients who had attempted suicide had CSF HVA/5-HIAA ratios that were nearly 50% those of the control subjects. The combinations of nonsuppression on the dexamethasone suppression test and either a low CSF HVA level or a low CSF HVA/5-HIAA ratio were significantly more common among patients who had attempted suicide than among those who had not.     

Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide

Abstract

Objectives. Immunological differences have previously been associated with depression and suicidal behaviour. Several cytokines have been identified as potentially important in understanding the pathophysiology of mood disorders and suicidality. Here we aimed to identify new inflammatory biomarkers for suicide prediction. Methods. Plasma concentrations of interleukin (IL) 1-a , IL1-b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFNG), tumor necrosis factor-a (TNF-a), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) were measured in 58 suicide attempters with a high throughput automated biochip immunoassay system. Patients were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Suicide Intent Scale (SIS). All patients were followed up for cause of death. Results. We found significantly lower levels of VEGF in the seven patients who upon a mean follow-up of 13 years were found to have completed suicide. VEGF also showed a trend for negative correlation with the planning subscale of SIS. A trend could be shown for lower IL-2 and for higher IFNG levels in suicide victims. Conclusions. Our study provides further support for a role of inflammation in the pathophysiology of suicidality. VEGF may be related with suicide risk.