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.     

Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy

To study different aspects of regional pre-synaptic brain (123)I-beta-CIT uptake on serotonin and dopamine re-uptake sites in drug-free suicide attempters in comparison with age- and sex matched control subjects, single photon emission computed tomography (SPECT) measurements were analysed for regional serotonin re-uptake (5HTT) and dopamine re-uptake (DAT) capacity (binding potential, BP()) after i.v. (123)I-beta-CIT administration. All suicide attempters were examined concerning seriousness of the attempt, and DSM-IV diagnosis. Both suicide attempters and control subjects were tested for psychotropic drugs, and completed the Marke-Nyman Temperament (MNT) test, including solidity (level of impulsiveness/initiative) and validity (level of mental energy). We found no significant difference between suicide attempters and control subjects concerning the regional levels of 5HTT BP() or DAT BP(). However, in suicide attempters, but not controls, we found significant regional correlations between MNT variables and SPECT results. We interpret the discrepant findings in suicide attempters and control subjects to be due to a disability of the suicide attempters to regulate their serotonin and dopamine levels, e.g. in response to external stress.     

Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy

To study different aspects of regional pre-synaptic brain ¹²³I-β-CIT uptake on serotonin and dopamine re-uptake sites in drug-free suicide attempters in comparison with age- and sex matched control subjects, single photon emission computed tomography (SPECT) measurements were analysed for regional serotonin re-uptake (5HTT) and dopamine re-uptake (DAT) capacity (binding potential, BP) after i.v. ¹²³I-β-CIT administration. All suicide attempters were examined concerning seriousness of the attempt, and DSM-IV diagnosis. Both suicide attempters and control subjects were tested for psychotropic drugs, and completed the Marke-Nyman Temperament (MNT) test, including solidity (level of impulsiveness/initiative) and validity (level of mental energy). We found no significant difference between suicide attempters and control subjects concerning the regional levels of 5HTT BP or DAT BP. However, in suicide attempters, but not controls, we found significant regional correlations between MNT variables and SPECT results. We interpret the discrepant findings in suicide attempters and control subjects to be due to a disability of the suicide attempters to regulate their serotonin and dopamine levels, e.g. in response to external stress.     

Temperament traits in male suicide attempters and violent offenders.

With the purpose of comparing temperament traits in subjects who have been violent towards others and with subjects who have shown self-directed violence, 34 male suicide attempters and 34 male violent offenders were matched for age and psychiatric diagnosis. Violent offenders with a history of suicide attempts were excluded. Temperament traits were assessed by means of the Karolinska Scales of Personality. The temperament profiles of suicide attempters and violent offenders were very similar, with high trait anxiety and very low socialization. Violent offenders displayed significantly higher social desirability (P < 0.001). Suicide attempters tended to have higher indirect aggression and monotony avoidance. Impulsiveness, verbal aggression, and inhibition of aggression were within the normal range in both groups. There were substantial temperamental similarities between suicide attempters and violent offenders. In order to disentangle the differential mechanisms behind aggression towards self and others, we probably need to consider historical as well as current situation factors in a systematic way.     

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.     

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.     

Cholesterol concentrations in violent and non-violent women suicide attempters.

The aim of this study was to evaluate whether women with a history of violent suicide attempts have lower serum cholesterol concentrations than those who attempted suicide by non-violent methods. Our retrospective study used a case-control design to compare serum total cholesterol concentration, hematocrit, red blood cell count and body mass index (BMI) in women with a history of violent (n = 19) or non-violent (n = 51) suicide attempts and of non-suicidal controls (n = 70) matched by diagnosis and age. Analysis of covariance (ANCOVA) with age as the covariate was used to analyze differences in cholesterol levels in groups according to violence. Violence was found to be a significant factor (P = 0.016). Using the Scheffé test, a significant difference (P = 0.011) was revealed between the group of violent and non-violent suicide attempters and between the violent suicide attempters and the control group. Patients with a violent suicidal attempt have significantly lower cholesterol levels than patients with non-violent attempts and the control subjects. Our findings suggest that suicide attempts should not be considered a homogeneous group. They are consistent with the theory that low levels of cholesterol are associated with increased tendency for impulsive behavior and aggression and contribute to a more violent pattern of suicidal behavior.     

Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis.

BACKGROUND: There is strong evidence supporting a role for serotonin system dysfunction in the pathology of suicidal behavior. Many studies have examined the association between a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) and suicide but have yielded inconsistent results. Our goal here, by analyzing the cumulative data from primary literature, was to determine conclusively whether there is an association. METHODS: Three meta-analyses were performed. One compared the 5-HTTLPR polymorphism between suicidal subjects and normal control subjects; another compared suicide attempters with nonattempters of the same psychiatric diagnoses; the last one compared either violent or nonviolent suicidal subjects with normal control subjects. RESULTS: We found no association between 5-HTTLPR polymorphism and suicidal behavior (p =.379). When we compared subjects with the same psychiatric diagnoses, the genotypes carrying the s allele were significantly more frequent in suicide attempters than in nonattempters (p =.004). In addition, the s allele was associated with violent suicide (p =.0001) but not with nonviolent suicide (p = 1.00). CONCLUSIONS: Our results provide significant evidence supporting the association of the s allele of 5-HTTLPR polymorphism with suicidal behavior in the psychiatric population, also with violent suicide. These support a role for decreased serotonin transporter function in the vulnerability to suicide in a select population.     

Impaired decision making in suicide attempters

OBJECTIVE: The understanding of suicidal behavior is incomplete. The stress-diathesis model suggests that a deficit in serotonergic projections to the orbitofrontal cortex is involved in susceptibility to suicidal behavior. The orbitofrontal cortex has been implicated in decision making, a cognitive function dealing with complex choices that may be under serotonergic modulation. In this preliminary study, the authors assessed decision making in suicide attempters. METHOD: The authors used the Iowa Gambling Task to investigate patients with a history of violent (N=32) or nonviolent (N=37) suicidal behavior, patients suffering from affective disorders with no history of suicidal behavior (N=25), and healthy comparison subjects (N=82). Patients were assessed when they were not suffering from a current axis I disorder. The authors also assessed the correlation of Iowa Gambling Task performance with psychometric measures of impulsivity, hostility, anger, aggression, and emotional instability. RESULTS: Both groups of suicide attempters scored significantly lower than healthy comparison subjects, and violent suicide attempters performed significantly worse than affective comparison subjects. No significant differences were observed between the groups of suicide attempters or between the two comparison groups. The differences in performance could not be accounted for by age, intellectual ability, educational level, number of suicide attempts, age at first suicide attempt, history of axis I disorder, or medication use. Iowa Gambling Task performances were correlated positively with affective lability and with anger expression but not with impulsivity. CONCLUSIONS: Impaired decision making, possibly due to emotional dysfunction, may be a neuropsychological risk factor for suicidal behavior.     

Low serum cholesterol in violent but not in non-violent suicide attempters

Many previous studies have suggested that low or lowered serum cholesterol levels may increase the risk of mortality not due to somatic disease: principally, suicide and violent death. Because violent death is rare, some studies have investigated afterwards the relation between cholesterol levels and either suicide attempts in psychiatric populations or violence in criminally violent populations. However, none of these studies have compared cholesterol levels in violent and non-violent suicide attempters. The blood of 25 consecutive drug-free patients following a violent suicide attempt and of 27 patients following a non-violent suicide attempt by drug overdose was drawn in the 24 h following admission. Patients with a diagnosis of alcohol abuse and with cholesterol-lowering therapy were excluded. Age, sex, body mass index, psychiatric diagnosis and the physical conditions of the suicide attempt were investigated. Thirty-two healthy subjects were used as a control group. There were no differences between the groups in age, frequency of psychiatric diagnoses or body mass index. There was more women in the group of non-violent suicide attempters than in that of violent suicide attempters (P<0.001). In analyses controlling for sex and age, the serum cholesterol concentration was 30% lower (F(2,82)=15.8; P<0.0001) in the group of violent suicide attempters (147+/-54 mg/dl) than in the group of non-violent suicide attempters (209+/-38 mg/dl) or control subjects (213+/-46 mg/dl). Our results showed that low serum cholesterol level is associated with the violence of the suicide attempt and not with the suicide attempt itself. Further investigations are necessary to determine the usefulness of this easily accessible parameter as a potential risk indicator for violent acts such as violent suicidal behavior in susceptible individuals.     

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.     

Protective factors against suicidal behavior in depressed adults reporting childhood abuse

Most previous studies compared suicidal behavior in subjects with and without a history of childhood abuse, whereas less attention was paid to the comparison of suicide attempters and nonattempters among subjects reporting childhood abuse. To identify risk and protective factors against suicidal behavior, we compared suicide attempters with nonattempters among the sample of 119 depressed inpatients who reported childhood abuse. Compared with nonattempters, suicide attempters were younger, had more self-rated depression severity and suicidal ideation, higher trait aggression and more cluster B personality disorder comorbidity, less coping potential, and fewer moral objections to suicide (MOS)/religious beliefs. Logistic regression showed that more severe suicidal ideation and fewer MOS/religious beliefs were associated with suicidal acts in subjects with reported childhood abuse. Furthermore, suicidal ideation and MOS/religious beliefs were significantly inversely correlated. The results of this clinical study add support to previous reports that religious/spiritual coping could serve as an additional resource in prevention of suicidal behavior for subjects with reported childhood abuse.     

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 proposed model of the development of suicidal ideations

BackgroundSuicidal ideations may precede suicide attempts. They are of particular concern in psychiatric populations because psychopathology is a major risk factor for suicide. The factors affecting the development of suicide ideations may differ among psychiatric patients with and without a previous suicide attempt and individuals without a psychiatric diagnosis.ObjectivesThe aim of this study is to develop a model of suicide ideation in psychiatric patients and the general population.MethodThe study included 196 participants: 92 psychiatric patients with a previous suicide attempt (“attempters”); 47 psychiatric patients who had never attempted suicide (“non-attempters”); and 57 healthy control subjects. Data were collected on socio-demographic parameters, clinical history, and details of the suicide attempts. Participants completed a battery of psychological instruments assessing aggression–impulsivity, mental pain (including depression and hopelessness) and communication difficulties, in addition to negative life events. Findings were correlated with suicidal ideation by group.ResultsThe correlations of the different variables with suicidal ideation differed between suicide attempters and non-attempters; therefore, the model was analyzed separately for each group. The study yielded three major findings: negative life events had a significant effect on both anger-in and impulsivity in non-attempters but not in attempters; hopelessness moderately contributed to suicidal ideations in attempters but not in non-attempters; loneliness contributed significantly to depression in non-attempters but was less distressing in attempters.ConclusionThe mechanism underlying suicidal ideation appears to differ between psychiatric patients who have previously attempted suicide and those who have not, supporting a dual model of suicidal ideation. Although this is only a preliminary study, these findings are important for furthering our understanding of the process of transition of suicidal thoughts to completion of suicide. These results need further replication with a larger cohort of subjects.     

Suicidal behaviour in major depressive illness

We investigated past suicidal behaviour and family history of suicide in 713 inpatients with major depressive illness. A familial history of suicide (mainly violent) significantly increased the frequency of violent suicidal behaviour in depressive women; bipolar patients being more affected than unipolars. In depressed men, the presence of suicidal behaviour was not significantly affected by polarity. The occurrence of familial suicide significantly increased the risk of violent suicidal behaviour in male depressed attempters. The present study indicates that a familial history of violent suicide is associated with the presence of violent suicidal behaviour in major depressive patients.     

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.     

TPH and suicidal behavior: a study in suicide completers

An association between the gene that codes for tryptophan hydroxylase (TPH)-the rate-limiting enzyme in the synthesis of serotonin-and suicidal behavior has been investigated with some detail in samples of living subjects who attempted suicide. In this study, we investigated TPH and suicide completion, the most severe form of suicidal behavior. A relatively large sample of suicide completers (n = 101) was genotyped at three TPH loci (two polymorphisms in the promoter region, A-6526G and G-5806T, and one in intron 7, A218C) and compared to psychiatrically normal living controls (n = 129). Although no significant differences were found between groups for genetic variation at single loci, haplotype analysis revealed that one haplotype (-6526G -5806T 218C) was significantly more frequent among suicide cases than in normal controls (chi(2) = 11.30, df = 2, P = 0.0008; OR = 2.0 CI: 1.30-3.6). Further analyses suggested that this haplotype is particularly more frequent among subjects who committed suicide using violent methods. Similar results were observed in recent haplotype analyses in suicide attempters, which found that the equivalent of haplotype -6526G -5806T 218C was more frequent in impulsive attempters (Rotondo et al, Mol Psychiatry 1999; 4: 360-368). Our results replicate in suicide completers previous data observed in suicide attempters. These and other results continue to point to the substantial role that the gene that codes for TPH may play in the neurobiology of suicidal behavior.     

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.     

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.     

Suicide and violence in patients with major psychiatric disorders

The relationship between violence directed at the self and violence directed at others has intrigued psychiatrists for several decades. The goal of this study was to examine the relationship between suicide and violence against others in patients with major psychiatric disorders and to compare psychiatric symptoms associated with suicide in violent and non-violent patients. Subjects included physically assaultive psychiatric inpatients and a nonviolent comparison group. Physical and verbal assaults were recorded prospectively for 4 weeks. History of suicide attempts was obtained through chart review and patient interviews. The Brief Psychiatric Rating Scale was administered at the end of the 4 weeks by raters who were blind to both suicidal and violent behavior. The suicide attempters did not differ from the non-attempters on any measure of violent behavior or hostility. Suicide attempts were not accompanied by different symptoms in violent and non-violent patients; however, violence and suicide attempts were accompanied by dissimilar psychiatric symptoms. The physically assaultive patients presented with more severe positive psychotic symptoms than the non-assaultive patients. The suicide attempters, on the other hand, did not differ from non-attempters on psychotic symptoms, but presented with more severe depression and anxiety. The relationship between these symptoms and suicide attempts was noteworthy in its temporal stability, as most of the patients had attempted suicide many years prior to this study.