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.     

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.     

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.     

Monoamine metabolites in CSF and suicidal behavior

Cerebrospinal fluid concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were measured in 30 psychiatric patients who had attempted suicide and 45 healthy volunteers. The suicide attempters had a significantly lower CSF 5-HIAA level than the controls, especially those who had made more violent attempts. After adjustment for differences in body height and age between controls and patients, the difference in 5-HIAA level became even more marked. Concentrations of 5-HIAA also were lower than normal in suicidal patients who were not diagnosed as depressed at the time of lumbar puncture, while HVA levels were lowered only in the depressives. A follow-up study of these and 89 more patients (depressed and/or suicidal) revealed a 20% mortality by suicide within a year after lumbar puncture in patients with a CSF-HIAA level below the median.     

The Marke-Nyman Temperament (MNT) scale in relationship with monoamine metabolism and corticosteroid measures in suicide attempters

Abstract

Various monoaminergic measures as well as corticosteroid deviances have repeatedly been linked to depression or suicidal behavior. With the purpose to study these biological markers in relationship with temperament, the Marke-Nyman Temperament (MNT) questionnaire was administered in a sample of 89 suicide attempters. The subjects were diagnosed according to the DSM-III-R and subgrouped according to suicide method into “violent” and “nonviolent” attempters, and into “repeaters” (with previous attempt) and “nonrepeaters” (without previous attempts). The subjects were also subgrouped according to MNT patterns into 5 MNT clusters. Lumbar punctures were performed and the monoamine metabolites homovanillic acid (HVA). 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycole (MHFG) in the cerebrospinal fluid (CSF) were analysed. The levels of plasma cortisol and 24. urinary cortisol were determined and dexamethasone suppnssion tests (DST) were performed. The activity of the enzyme monoamine oxidase (MAO) in platelets was determined.

Among the alcoholic patients, the biological markers showed several specific correlations with temperament. In this group. low Solidity (reflecting impulsiveness) was significantly associated with low levels of CSF HVA. CSF 5-HIAA. urinary cortisol and low platelet MAO activity. The Stability (reflecting emotional distance towards others) was significantly and positively associated with urinary cortisol and platelet MAO activity. This seems to reflect the two previously described subgroups of alcoholism, with early and late onset, respectively.

In the whole sample, we found a positive correlation between urinary cortisol and Stability. The biological markers showed no clear differences between the MNT clusters. We could not replicate earlier findings of an association between impulsiveness (low solidity) and low levels of 5-HIAA or low MAO activity in platelets in the whole sample of suicide attempters.     

Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts

Magnesium and calcium concentrations were measured in the cerebrospinal fluid (CSF) of 15 neurological controls and 41 psychiatric patients suffering from major depression (n = 16), schizophrenic disorder (n = 15), or adjustment disorder (n = 10). All subjects were women 19-67 years of age and free from drugs at the time of the study. CSF was evaluated for 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol (CS) levels, and all patients received a dexamethasone suppression test (DST) following lumbar puncture. CSF calcium levels did not differ among groups, although we found a trend toward higher mean levels in both depression and schizophrenia. By contrast, CSF magnesium was found to be significantly lower in both depression and adjustment disorder; if, however, patients who had made suicide attempts were excluded, the difference became insignificant. Patients who had made suicide attempts (by using either violent or nonviolent means) had significantly lower mean CSF magnesium level irrespective of the diagnosis. CSF calcium did not correlate with magnesium, 5-HIAA, HVA, CS, global severity, therapeutic response, or DST, but CSF magnesium correlated significantly with CSF 5-HIAA, especially after correcting for age and body height. Both variables seemed to be primarily related to recorded suicide attempts, but decreased magnesium was not limited to violent cases.     

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.     

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 5HIAA and personal and family history of suicide in affectively ill patients: a negative study

Personal and family histories of suicidality were gathered in 45 patients who met Research Diagnostic Criteria for major affective disorder (n = 32, bipolar; n = 13, unipolar) and compared to CSF values of 5HIAA obtained by two different assays (n = 20, fluorometric; n = 25, high performance liquid chromatography). In separate analyses of the two assay groups, patients who had made a suicide attempt were not significantly different from those who had not in terms of 5HIAA value or family history of suicidality. Furthermore, in suicide attempters, 5HIAA was unrelated to the severity of the attempt.     

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.     

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.     

Natural killer cell activity and csf monoamine metabolites in suicide attempters

Abstract

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD 16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

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。     

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.     

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     

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 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.     

A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

Platelet MAO activity and monoamine metabolites in cerebrospinal fluid in depressed and suicidal patients and in healthy controls

Platelet monoamine oxidase (MAO) activity and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were simultaneously measured in 20 currently depressed patients, 11 recovered depressed patients, 15 nondepressed suicide attempters, and 42 healthy control subjects. Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups. Suicide attempters had significantly lower CSF 5HIAA than nonsuicidal patients.