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.     

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 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.     

Suicidal Intent Among Young Suicides in Rural China

To understand psychometric characteristics of Beck Suicide Intent Scale (SIS) and different characteristics of suicides between high and low intent in Chinese culture. Data of 386 suicides and 416 living controls aged 15–34 years were used to analyze psychometric characteristics of SIS with 6 items. SIS with 6 items had high reliability and validity. Different characteristics were found between suicides with high intent and low intent. Hopelessness, depression, impulsivity, and approach coping skill were common factors of suicide with high and low intent. Education years, marriage, social support, and mental disorders were specific factors of suicide with low intent. High intent suicides had different characteristics from low intent suicides. SIS with 6 items is suitable for use in young rural China.     

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.     

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.     

Temperaments in completed suicides: Are they different from those in suicide attempters and controls?

BackgroundTemperaments in completed suicides have never been assessed whereas there is substantial research on temperaments in attempted suicides and psychiatric patients.MethodsThe significant others of 18 completed suicides participated in this study in order to provide an assessment of temperaments, hopelessness, depression and the suicide risk of their loved ones. The data were compared with data from 244 psychiatric patients of whom 83 had attempted suicide in the previous month. The following instruments were used: the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire (TEMPS-A), the Beck Hopelessness Scale (BHS), the Gotland Scale for Male Depression (GSMD), and the Mini International Neuropsychiatric Interview (MINI) module for assessing suicide risk.ResultsIndividuals who died by suicide more frequently had scores of 9 or higher on the BHS and higher MINI suicide risk scores compared with patients with mood disorders who had not attempted suicide in the previous month. Completed suicides also had lower scores on the TEMPS-A Cyclothymia and Anxiety scales and on the MINI suicide risk scale than mood disorder patients with a recent suicide attempt.LimitationsProxy assessment of variables through survivors can result in underestimation of psychiatric morbidity and other parameters investigated, and limits the generalization of our resultsConclusionsOur study adds information about temperamental subtypes and other variables in completed suicides and points to their difference from attempted suicides and non-suicidal psychiatric patients.     

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.     

Patients' evaluation of their psychiatric consultation after attempted suicide

Few studies have previously investigated patients' evaluation of their psychiatric consultation after attempted suicide. The aim of the present study was to examine the patients' view of their psychiatric consultation after a suicide attempt. Of a systematic sample of 114 suicide attempters in Helsinki, 73 subjects were referred to psychiatric consultation at an emergency room or department, and 53 of these evaluated the consultation received. Half of these suicide attempters considered their psychiatric consultation had occurred too soon after the attempt. Those whose prior attitude toward the consultation was indifferent had higher Hopelessness Scale (HS) and Beck Depression Inventory (BDI) scores than those who were positive. Psychiatric assessment should not take place before the patient has recovered from toxic effects caused by any overdose attempt. Suicide attempters with severe depression and hopelessness are likely to be those most indifferent to the prospect of psychiatric consultation. The presence of severe depression or hopelessness should not deter active evaluation and treatment.     

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.     

Who are likely to attempt suicide again? A comparative study between the first and multiple timers

BackgroundVarious explanations account for suicide incidents, and some patients continue to attempt afterwards and others never again. The suicide mortality rate increases with the number of serious attempts. The prevention of secondary attempt of suicide should be an important approach to reduce suicide mortality. However, the characteristics of the targeted population of repeated suicide attempters are understudied.MethodsThis was a cross-sectional data collection from hospital emergency room from patients who had either attempted suicide for the first time (n = 721) or for two or more times (n = 70). The subjects were between 14 and 53 years old and comprised 293 males and 498 females. In-depth interview was conducted for each suicide attempter with a semi-structural protocol. Demographic and social-psychological characteristics were compared between the two groups of suicide attempters. Logistic regression was used to identify independent predictors of multiple attempts.FindingsThe two groups only differed in religion factor among demographic characteristics and multiple suicide attempters group have a higher percentage of subjects who reported to have a religion affiliation than first time suicide attempters. Multiple attempters were more likely to have family suicide history, physical illness, mental disorder, higher scores on Beck Hopelessness Scale (BHS) and Suicide Intent Scale (SIS) and lower scores on Duke Social Support Scale (DSSI). In the final regression model, family history of suicide, mental disorder, hopelessness and social support emerged as significant predictors of multiple suicide attempts.ConclusionSuicide attempters that have mental disorder, family history of suicide, higher level of hopelessness and lower level of social support are more likely to re-attempt suicide again. Social and clinical interventions may have to also focus on this sub-group of patients with these characteristics to effectively reduce suicide mortality rate.     

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.     

CSF 5-HIAA and the rorschach test in patients who have attempted suicide.

Two independent measures, 5-HIAA and the Rorschach Suicide Constellation (S-CON), both related to suicide, were studied in an attempt to explore any relationship between the two. Lumbar puncture and the Rorschach were performed in standardized manner on 38 consecutive psychiatric inpatients, who had made a recent suicide attempt. Low CSF 5-HIAA was significantly related to the S-CON (rs = -.517, p = .033) and the Vista variable in the S-CON appeared to play an important role for the correlation. The results indicate that suicide attempters with low CSF 5-HIAA in this sample tended to experience more discomfort and pain during self-inspection. These results raise questions whether shame may be involved in the psychobiology of suicide.     

Severity of personality disorders and suicide attempt

Objective: Severity of personality disorders (PDs) may be more useful in estimating suicide risk than the diagnosis of specific PDs. We hypothesized that suicide attempters with severe PD would present more attempts and attempts of greater severity/lethality. Method: Four hundred and forty‐six suicide attempters were assessed. PD diagnosis was made using the International Personality Disorder Questionnaire – Screening Questionnaire. PDs were classified using Tyrer and Johnson’s classification of severity (no PD, simple PD, diffuse PD). Severity/lethality of attempts was measured with the Suicide Intent Scale, Risk‐Rescue Rating Scale and Lethality Rating Scale. Results: Attempters with severe (diffuse) PD had more attempts than the other groups. After controlling for age and gender, this difference remained significant only for the younger age group and women. There was no relationship between severity of PDs and severity/lethality of attempts. Conclusion: Younger female attempters with severe PD are prone to repeated attempts. However, the severity of PD was not related to the severity/lethality of suicide attempts.     

Prediction of suicide intent in hospitalized parasuicides: reasons for living, hopelessness, and depression.

This study examined the risk prediction efficiency of the Reasons for Living Inventory Survival and Coping Beliefs Scale, Beck Hopelessness Scale, Beck Depression Inventory, and the Life Experiences Survey with a sample of 51 newly hospitalized parasuicides. The index of suicidal potential chosen for this study was suicide intent as measured by Beck's Suicide Intent Scale. Regression analyses indicated that the Survival and Coping Beliefs Scale emerged as the single most important predictor of suicide intent. Hopelessness and depression made secondary and nonsignificant contributions. Hopelessness was a significant predictor of suicide intent when analyzed apart from Survival and Coping Beliefs, but not among a subsample of 43 repeat parasuicides. Classification analyses showed that neither hopelessness nor survival and coping beliefs were accurate at classifying low- or high-intent parasuicides. Factors contributing to the efficacy of survival and coping beliefs as a risk prediction index are discussed, as is the false-negative dilemma in suicide risk assessment and prediction.     

CSF 5-HIAA and DST non-suppression — Orthogonal biologic risk factors for suicide in male mood disorder inpatients

Two biomarkers of suicide risk; non-suppression in the dexamethasone suppression test (DST) and low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been reported to be predictors of suicide in mood disorders. The interrelation of the two systems seems to be different in suicide attempters compared with depressed inpatients who have not made a suicide attempt, indicating that the two biomarkers may be seen as independent. This investigation examined the interrelation of low CSF 5-HIAA and DST non-suppression in suicide victims with mood disorder. Fifty-eight mood disorder inpatients not receiving any treatment with antidepressants underwent lumbar puncture and the DST. Plasma cortisol levels at 8:00 a.m., 4:00 p.m. and 11:00 p.m. were analysed in relation to CSF 5-HIAA. All patients were followed up for causes of death and suicides were verified with death certificates. During follow-up (mean 21 years), 11 (19%) patients had committed suicide. In male suicide victims (n = 6), the serum cortisol level at 4:00 p.m. showed a significant positive correlation with CSF 5-HIAA. Low CSF 5-HIAA predicted all early suicides (within 1 year), whereas all males who committed suicide after 1 year were DST non-suppressors. In female suicide victims (n = 5), the post-DST serum cortisol did not correlate with CSF 5-HIAA. Low CSF 5-HIAA and DST non-suppression are orthogonal biologic risk factors for suicide in male mood disorder inpatients. CSF 5-HIAA is associated with short-term suicide risk; dysregulation of the hypothalamic-pituitary-adrenal axis seems to be a long-term suicide predictor.     

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.     

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.     

Survival analysis of suicide risk after attempted suicide

Survival analysis of suicide risk by sex and age after attempted suicide was studied in a cohort of 1573 suicide attempters referred to the psychiatric emergency room at the Karolinska Hospital from 1981 to 1988. The time course of suicide risk and the overall prognosis after attempted suicide and, in particular, the possible usefulness of sex and age as risk factors for the prediction of suicide risk after attempted suicide was analyzed. Nearly two thirds of the sample were women and most of the suicide attempters were young (in their twenties and thirties), and the median age was 35 years. The overall mortality after a 5-year mean observation period after attempted suicide was 11%, and the suicide mortality was 6 %. The suicide risk after attempted suicide among men (8.3%) was nearly twice the female suicide risk (4.3%). Age as a possible suicide risk factor was analyzed for each sex separately by median split subgrouping. It was concluded that both older and younger male suicide attempters are at high risk of suicide (7% and 10% respectively), and older women are at higher risk than younger (6%, vs 2%). The suicide risk is particularly high during the first year after the suicide attempt. The high suicide risk group of young adult male suicide attempters is one of the main feasible targets of psychiatric intervention research programs on suicidal behavior. Suicide among young men is a major cause of years of life lost.