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.     

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.     

The relationship between CSF HVA/5-HIAA ratio and suicide intent in suicide attempters.

There is a need to find stable biomarkers for suicidal behavior and suicide prediction. Reduced homovanillic acid/5-hydroxyindolacetic acid (HVA/5-HIAA) ratios in cerebrospinal fluid (CSF) in depressed suicide attempters have been reported. Suicide intent is a predictor of repetition of attempts and suicide. In the present study we investigated the relationship of HVA/5-HIAA ratio to the scales rating suicide intent and depressive symptoms. Fifteen consecutive medication-free male suicide attempters admitted to a psychiatric ward at the Karolinska Hospital and eight healthy male volunteers underwent lumbar puncture and had the CSF monoamine metabolite levels assayed. Patients were assessed with the Beck Suicide Intent Scale (SIS), the Montgomery Asberg Depression rating Scale (MADRS) and the Chapman Scale of Anhedonia. Within the suicide attempter group, HVA/5-HIAA ratio was significantly associated with the Suicide Intent Scale (SIS), but not with the MADRS scale or the Chapman Scale of Anhedonia indicating that the HVA/5-HIAA ratio may be a biomarker of suicide intent.     

Non-Suicidal Self-Injury and Interpersonal Violence in Suicide Attempters

The current study compared characteristics of suicidal behavior and interpersonal violence in suicide attempters with and without a history of non-suicidal self-injury (NSSI). A total of 100 suicide attempters were assessed with Karolinska Interpersonal Violence Scale (KIVS) and Karolinska Suicide History Interview concerning interpersonal violence and NSSI. There was a high degree of comorbid NSSI in suicide attempters (44%). Suicide attempters with NSSI-history reported more interpersonal violence as adults and more severe suicidal behavior compared to suicide attempters without NSSI. Comorbid NSSI was related to severity of suicidal behavior in a gender specific manner. Comorbid NSSI in suicide attempters may increase suicide and violence risk.     

Cholesterol and the “Cycle of Violence” in attempted suicide

An association between low levels of serum cholesterol and violent or suicidal behaviour has frequently been reported. However the role of serum cholesterol in the cycle of violence (Widom, 1989) has not been studied. The aim of this study was to investigate association between exposure to violence during childhood and used adult violence in suicide attempters with low and high serum cholesterol levels. 81 suicide attempters were assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behaviour in childhood (between 6 and 14 years of age) and during adult life (15 years or older). We used median split to dichotomise groups below and above median serum cholesterol. In patients with serum cholesterol below median, the correlation between exposure to violence as a child and used adult violence was significant (rho=0.52, p=0.002), while in patients with serum cholesterol above median, the correlation between exposure to violence as a child and expressed violent behaviour as an adult was not significant (rho=0.25, p=0.2). Comorbid substance abuse predicted violent behaviour as an adult only in patients with serum cholesterol above median. Serum cholesterol may modify the effect of the “Cycle of Violence”.     

伴人格障碍自杀未遂者临床特点研究

目的：探讨伴人格障碍自杀未遂者的临床特点。方法：对108名自杀未遂急诊入院的患者按CCMD-2-R进行人格障碍的诊断，分为伴人格障碍组和不伴人格障碍组，对两组的社会人口学资料和临床资料进行统计，并进行自杀意图量表及自杀企图冲动性和致死性的测定，将有关项目作对比分析。结果：有40（37.04％）名自杀未遂者伴发人格障碍，伴人格障碍自杀未遂者与不伴人格障碍自杀未遂者，有较多的既往自杀未遂史和精神科治疗史，自杀意图和自杀企图致死性较低，冲动性较高。结论：对伴人格障碍自杀未遂者应给予特别对待和积极治疗。     

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.     

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.     

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.     

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.     

Gonadal axis hormones in psychiatric male patients after a suicide attempt

Epidemiological and clinical studies support the view that aggressive acts like suicidal and violent behaviors share a common substrate. Certain aspects of violence in males have been related to high testosterone levels, but the relation of testosterone to attempted suicide has not been studied until now. We estimated plasma levels of testosterone (T), LH, and FSH in 80 male subjects after a suicide attempt and in whom a psychiatric assessment was done during their hospitalization. Suicide intent was evaluated in 72 subjects. A group of 56 healthy males in the same age range served as control. As a group, attempters showed significantly lower T levels, marginally higher LH, and normal FSH compared to controls. The attempters who used violent methods (26 subjects) had T levels even lower than the non-violent (drug overdose) subgroup. Comparisons of T levels of subgroups according to the (main) drug ingested (analgesics, benzodiazepines, antidepressants, neuroleptics, or other drugs) did not reveal any significant drug effect. In relation to diagnosis, the lowest T levels were found in the subgroup with schizophrenia (29 subjects). The T levels of this subgroup were also significantly lower compared to those of a group of 31 male schizophrenic patients, hospitalized and treated with neuroleptics. If the influence of post-attempt stress and medical condition on plasma T could be ruled out, low plasma T may prove to be a biological predictor of attempt, at least in male schizophrenic patients. Nevertheless, the findings differentiate suicidal behavior from other aggressive/violent behaviors and do not support the notion that suicidal and aggressive behaviors are manifestations of the same impulse.     

A comparison of the medical lethality of suicide attempts in bipolar and major depressive disorders

Objectives:  Among mood disorders, bipolar disorder (BPD) is often noted to involve the highest rates of suicide attempts and possibly of completion. This study sought to determine whether suicide attempters with BPD exhibit suicide attempts with higher lethality than attempters with major depressive disorder (MDD) and to explore differences in clinical features associated with suicidal acts.
Methods:  Mood disordered suicide attempters were interviewed about Axis I and II diagnoses, lifetime history of suicide attempts, suicidal intent, suicidal ideation, the medical lethality of their most severe suicide attempt, severity of depression, hopelessness, lifetime aggression, and impulsivity.
Results:  The maximum lethality of suicidal acts tended to be higher among BPD attempters compared with those with MDD. However, there were no differences in the number of suicide attempts, intent to die or suicidal ideation. Suicide attempters with BPD reported higher levels of aggression and impulsivity but less hopelessness compared with MDD attempters. These differences could not be explained by Cluster B personality disorder comorbidity. Of note, within the BPD group, but not the MDD group, males reported suicidal acts with higher lethality. Multivariate analyses suggested that risk for more lethal suicide attempts is associated with BPD and male sex and that bipolar males appear to be especially vulnerable to these behaviors.
Conclusions:  Males with BPD make more lethal suicide attempts than females with BPD, an effect not observed among the MDD sample. Our findings suggest that higher rates of suicidal behavior in BPD may be due to a specific effect of BPD on males, leading to more dangerous suicidal behaviors. This effect, together with the larger proportion of males in the BPD group compared with the MDD group may lead to higher rates of reported attempted and completed 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.     

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 turnresults in a seemingly normal stress system.     

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.     

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.     

Relationships between attempted suicide, temperamental vulnerability, and violent criminality in a Swedish forensic psychiatric population.

The relationship between suicide attempts and different vulnerability factors was investigated in 61 male subjects during forensic psychiatric examination. Personality traits and psychopathy were determined by means of the Karolinska Scales of Personality (KSP) and the Psychopathy Checklist-Revised (PCL-R). Clinical diagnoses were determined by the use of Structured Clinical Interview for DSM-III-R (SCID). Platelet monoamine oxidase (MAO) activity was investigated in 58 subjects.Suicide attempters had extremely low socialization and high impulsive aggression. This was independent of a history of repeatedly criminal violence or not. They had higher PCL-R scores and lower levels of platelet MAO activity than non-attempters. No relationship was found between suicide attempts and repeated violent criminality. However, among the subjects with repeated criminal violence there was a highly significant difference between suicide attempters and non-attempters, indicating different personality profiles in violent offenders with and without suicidal behavior. Suicidal behavior was significantly associated with borderline personality disorder, but not with any other single DSM-III-R disorder. The results show a far more severe personality disturbance in suicide attempters than in other violent patients in this type of population. Suicidal behavior should therefore be evaluated and treated per se.     

Skin conductance habituation and cerebrospinal fluid 5-hydroxyindoleacetic acid in suicidal patients

The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and psychophysiologic variables, such as habituation of the skin conductance response, were measured in 35 drug-free, suicidal inpatients. Twenty-four patients were hospitalized after a suicide attempt, and another 11 had suicidal ideation. The suicide attempters were classified into nonviolent (drug overdoses taken orally, or a single wrist cut) and violent (all other methods). As in previous studies, the suicide attempters had significantly lower CSF concentrations of 5-HIAA compared with healthy, matched controls. The distribution of habituation rate was bimodal (slow and fast habituators). All violent attempters were fast habituators, as were all four patients who in a one-year follow-up were found to have completed a suicide (all by violent methods). The lowest frequency of fast habituators was found in the group of patients with suicidal ideation. There was no correlation between CSF 5-HIAA and habituation rate. A combination of these two variables yielded a highly significant correlation with type of suicide behavior, both retrospectively and prospectively.     

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.     

ABCB1 gene polymorphisms and violent suicide attempt among survivors

IntroductionThose suicide attempters that choose violent methods dramatically diminish the possibility of survival. Completed suicide using violent means, which is common among first-time suicide attempters, was recently found to be more likely among T allele carriers in the three most common ABCB1 SNPs, encoding for P-gp. Thus, this study examined, for the first time, whether these ABCB1 SNPs were associated with the use of violent means among survivors of a suicide attempt.Material and methodsSuicide attempters (n = 578, 87.4% women; of whom 16.6% committed a violent intent) were genotyped for exonic SNPs in the ABCB1 (C1236T, G2677T/A, C3435T). The relations of the three genotypes and of the TTT haplotype with the use of a violent suicide method were evaluated separately. The impact of confounds on these variables was controlled.ResultsA higher frequency (p = 0.02) of suicide attempters using violent methods was found among those carrying the ABCB1 haplotype (1236TT-2677TT-3435TT). Since gender and number of previous suicide attempts were identified as confounds, the relation was tested in the subset of women who were first-time attempters or second- and more-time attempters. The ABCB1 haplotype increased the risk more than three times in those women attempting a violent suicide for the first time (OR = 3.6; CI95%: 1.08–12.09; p = 0.04).DiscussionThe ABCB1 haplotype (1236TT-2677TT-3435TT) was related to the use of a violent suicide attempt method. Genotyping for these three ABCB1 SNPs may be helpful to detect people at risk of first suicide intents using violent methods.