Combining the Suicide Intent Scale and the Karolinska Interpersonal Violence Scale in suicide risk assessments.

BACKGROUND: High suicide intent, childhood trauma, and violent behavior are risk factors for suicide in suicide attempters. The aim of this study was to investigate whether the combined assessment of suicide intent and interpersonal violence would provide a better prediction of suicide risk than an assessment of only suicide intent or interpersonal violence. METHODS: This is a cohort study involving 81 suicide attempters included in the study between 1993 and 1998. Patients were assessed with both the Suicide Intent Scale (SIS) and the Karolinska Interpersonal Violence Scale (KIVS). Through the unique personal identification number in Sweden, patients were linked to the Cause of Death Register maintained by the Swedish National Board of Health and Welfare. Suicides were ascertained from the death certificates. RESULTS: Seven of 14 patients who had died before April 2013 had committed suicide. The positive predictive value for the Suicide Intent Scale alone was 16.7 %, with a specificity of 52 % and an area under the curve of 0.74. A combined assessment with the KIVS gave higher specificity (63 %) and a positive predictive value of 18.8 % with an AUC of 0.83. Combined use of SIS and KIVS expressed interpersonal violence as an adult subscale gave a sensitivity of 83.3 %, a specificity of 80.3 %, and a positive predictive value of 26 % with an AUC of 0.85. The correlation between KIVS and SIS scores was not significant. CONCLUSIONS: Using both the the SIS and the KIVS combined may be better for predicting completed suicide than using them separately. The nonsignificant correlation between the scales indicates that they measure different components of suicide risk.

"Serotonin depression"--a biochemical subgroup within the affective disorders?

The distribution of 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid of 68 depressed patients was bimodal. Twenty-nine percent of the patients were in the lower mode, with a concentration of 5-HIAA below 15 nanograms per milliliter. Although there were no differences in overall severity of depression between the two modes, there was a significant correlation between the concnetration of 5-HIAA and severity of depression in the lower, but not in the upper, mode. The finding suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover.

Stress and burnout in psychiatric professionals when starting to use dialectical behavioural therapy in the work with young self-harming women showing borderline personality symptoms.

The aim of the study was to investigate how starting to use dialectical behavioural therapy (DBT) in the work with young self-harming women showing symptoms of borderline personality disorder affected the psychiatric professionals (n = 22) experience of occupational stress and levels of professional burnout. The study was carried out in relation to an 18-month clinical psychiatric development project, and used a mix of quantitative and qualitative research methods [a burnout inventory, the Maslach burnout inventory-General Survey (MBI-GS), free format questionnaires and group interviews]. The result confirms previous reports that psychiatric health professionals experience treatment of self-harming patients as very stressful. DBT was seen as stressful in terms of learning demands, but decreased the experience of stress in the actual treatment of the patients. The teamwork and supervision were felt to be supportive, as was one particular facet of DBT, namely mindfulness training which some therapists felt also improved their handling of other work stressors not related to DBT. The inventory for professional burnout, the MBI-GS, showed no significant changes over the 18-month period, although there was a tendency for increased burnout levels at the 6-month assessment, which had returned to baseline levels at 18 months.

5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor?

The incidence of suicidal acts was studied in 68 depressed patients and related to the level of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid. The distribution of 5-HIAA levels was bimodal. Patients in the low 5-HIAA mode (below 15 ng/ml) attempted suicide significantly more often than those in the high mode, and they used more violent means. Two of the 20 patients in the low mode, and none of the 48 patients in the high mode died from suicide.

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.

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.

Clomipramine treatment of obsessive-compulsive disorder. I. A controlled clinical trial.

The effect of clomipramine hydrochloride in severe obsessive-compulsive disorder (OCD) was compared with that of nortriptyline hydrochloride and placebo in a five-week randomized, double-blind trial. Clomipramine, but not nortriptyline, was superior to placebo in interview-based ratings of severity of OCD. The effect was not clear-cut until after five weeks of treatment. When clomipramine was given openly to 22 patients after the end of the controlled trial, half of the patients responded to the drug. The response could not be predicted from severity or duration of illness, sex or age of the patient, or presence or absence of secondary depressive symptoms. The amelioration with clomipramine was not sustained if the drug was withdrawn.

Cortisol in the CSF of depressed and suicidal patients.

Cortisol concentrations in CSF were measured by radioimmunoassay in healthy controls, depressed patients, patients who had attempted suicide but were not depressed, and obsessive-compulsive patients. The factors that contributed most to the variance in CSF cortisol levels were a diagnosis of depression, height, and important life changes during the six months preceding the investigation. Depression was by far the most important factor. The depressed patients had significantly higher CSF cortisol levels than the controls. In obsessive-compulsive and depressed patients treated with clomipramine hydrochloride, the levels were significantly correlated with mean urinary cortisol excretion. Of the three monoamine metabolites measured, only 5-hydroxy-indoleacetic acid level was weakly correlated with CSF cortisol level. This correlation was confined to the depressed patients and could be accounted for by the common correlation with height.

Clomipramine treatment of obsessive-compulsive disorder. II. Biochemical aspects.

Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the dopamine metabolite homovanillic acid, and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol were measured in CSF before and after three weeks' treatment of severe obsessive-compulsive disorder with clomipramine hydrochloride. Patients who responded to clomipramine treatment had significantly higher CSF levels of 5-HIAA before treatment. The amelioration of obsessive-compulsive symptoms was positively correlated to the reduction of CSF concentrations of 5-HIAA during clomipramine treatment but negatively correlated to plasma concentrations of clomipramine. Reduction of CSF concentrations of 5-HIAA, which probably reflects drug action on central serotonin neurons, was maximal at a plasma clomipramine concentration of about 300 nmole/L. At higher levels, the reduction of CSF levels of 5-HIAA was smaller. The antiobsessive effect of clomipramine may be connected to its capacity to inhibit serotonin uptake.

Effects of antidepressant treatments on platelet tritiated imipramine binding in major depressive disorder.

The effects of four antidepressant treatments on platelet tritiated imipramine binding have been studied in 51 hospitalized patients with severe major depressive disorder. There was an increase in maximum binding (Bmax) during the first week of treatment with antidepressants and electroconvulsive therapy, which was further magnified after three weeks' treatment with the serotonin uptake blockers alaproclate and zimeldine hydrochloride, but the Bmax values returned to baseline levels with nortriptyline hydrochloride and electroconvulsive therapy. The equilibrium dissociation affinity constant (Kd) did not change with any of the treatments. On reexamination one or two years after admission to the study, Bmax had not reached control values in clinically recovered, drug-free patients. Low pretreatment Bmax was associated with delusions during illness and with a poor long-term clinical outcome. There was no correlation between binding parameters and monoamine metabolite concentrations in the cerebrospinal fluid, either before or during treatment.

Memory effects of clomipramine treatment: relationship to CSF monoamine metabolites and drug concentrations in plasma.

Performance on tasks tapping automatic and voluntary aspects of memory, attention, and motor speed was examined in 14 patients with major depressive disorder, before and after 3 weeks of treatment with clomipramine (150 mg/day), a potent serotonin and noradrenaline uptake blocker with anticholinergic side effects. Performance on tasks requiring frontal functions improved or did not change, whereas verbal learning and retention, where hippocampal functioning is critical, were impaired. The latter tasks were negatively related to cerebrospinal fluid (CSF) 5-HIAA levels and plasma concentration of clomipramine. The results provide further support for the regulatory role of monoaminergic systems in cognition. Furthermore, we found the automatic-voluntary capacity distinction less heuristically useful. Physiological mechanisms regulating different aspects of cognition and memory appeared to be more closely related to the type of task used than to its capacity-demanding properties.

Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine.

The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawn from the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite.

No association between a promoter dopamine D(4) receptor gene variant and schizophrenia.

The dopamine D(4) receptor has been implicated in the pathogenesis of schizophrenia. An association between a putative functional promoter polymorphism (-521C/T) in the dopamine D(4) receptor gene (DRD4) and schizophrenia was recently reported. In the present study, patients with schizophrenia (n = 132) and control subjects (n = 388) were analyzed with respect to the DRD4 - 521C/T polymorphism. No significant case control differences emerged. The present results do not support a major role for DRD4 in the etiology of schizophrenia among Caucasians from Sweden.

No association between serotonin transporter gene polymorphisms and personality traits.

Human family and twin studies have established considerable heritable components in personality traits as assessed by self-report questionnaires. Recently, an association between a functional polymorphism in the upstream regulatory region of the serotonin transporter gene and neuroticism-related personality traits was reported. Two different serotonin transporter polymorphisms including the previously associated variant were genotyped in two samples of healthy Swedish subjects (n = 127 and n = 178, respectively) assessed with the Karolinska Scales of Personality (KSP) inventory. No statistically significant association between serotonin transporter polymorphisms and any of the eight neuroticism-related KSP scales was found. Thus, the previously reported association between serotonin transporter alleles and neuroticism-related personality traits could not be replicated in the present study.

Therapeutic effects of serotonin uptake inhibitors in depression.

Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.

Circadian rhythm of serotonin transport in human platelets.

The circadian rhythm of serotonin active transport in human platelets was investigated in ten healthy men, aged 27-35 years. Blood was collected at 08.00, 14.00, 20.00, 02.00 and 08.00 hours the next morning. Simultaneous evaluation of the mean platelet volume, platelet distribution width, platelet distribution skewness and platelet number in whole blood was performed. Km and Vmax for serotonin transport varied considerably among individuals over 24 h. However, the mean values and distribution of these kinetic parameters were reduced at 02.00 hours. All platelet size or number parameters were stable and normal over 24 h; therefore, the reduction in mean Km and Vmax values at 02.00 h is not related to morphological platelet differences but either to platelet intrinsic factors or plasmatic variables. Knowledge of the affinity and capacity of serotonin transport throughout the diurnal cycle is important for future comparisons with depressed patients as well as other hormonal rhythms in patients and healthy humans.

Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia.

Genetic factors and dopamine receptor dysfunction have been implicated in the pathophysiology of schizophrenia. Recently, an association between a putative functional promoter polymorphism (-141C Ins/Del) in the dopamine D2 receptor gene and schizophrenia was reported. We investigated unrelated Swedish schizophrenic patients (n = 129) and control subjects (n = 179) for the same polymorphism. Similarly to a previous Japanese report, the - 141C Del allele frequency was significantly lower in patients than controls (chi2=4.4, 1 df, p<0.05; odds ratio 0.49, 95% confidence interval 0.26-0.91). The present and previous results may indicate that the -141C Ins/Del dopamine D2 receptor gene polymorphism affects susceptibility to schizophrenia.

No association between serotonin 2A receptor gene variants and personality traits.

Among theories of biological underpinnings to personality traits, different mechanisms of the serotonergic system are perhaps the most common factors suggested to influence individual differences in personality traits. We have investigated two frequent variants in the serotonin 2A receptor gene (5-HT2A) and personality traits. Healthy Swedish subjects (n = 304) were assessed with the Karolinska Scales of Personality (KSP) inventory. After correction for multiple testing, no significant differences were found. We conclude that the investigated 5-HT2A gene variants do not significantly influence personality as assessed by the KSP in the present population.

Androgen receptor trinucleotide repeat polymorphism and personality traits.

Human family and twin studies have established considerable heritable components influencing individual differences in personality traits as assessed by self-report questionnaires. We have investigated a trinucleotide repeat polymorphism in the androgen receptor gene and personality traits. Healthy Swedish subjects (n = 335) were assessed with the Karolinska Scales of Personality inventory. There were tendencies (P > or = 0.006) in some scales indicating possible relationships between the androgen receptor allele length and personality traits related to dominance and aggression. However, after correction for multiple testing, no significant differences were found. We conclude that no significant association could be found between the androgen receptor polymorphism investigated and any personality trait, although the tendencies found are worthwhile subjects for replication attempts.

Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies.

Studies of neurotransmitter metabolites in cerebrospinal fluid (CSF) were initially focused on depressive illness. Although several studies have demonstrated low concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid (HVA), in depressed patients, these early studies may have been biased by concomitant administration of antidepressant drugs (which tend to lower CSF 5-HIAA), amount of CSF drawn (there is a concentration gradient for both metabolites), and selection of control subjects. Once these methodological details are controlled for, the differences between depressed patients and controls are unimpressive. However, there is a remarkably consistent association between low concentrations of CSF 5-HIAA and suicidal behavior, as evidenced by over 20 studies. The association is not confined to depressive illness but has also been found in schizophrenia, personality disorder, and certain impulse control disorders (but, interestingly, not in bipolar disorder). A low concentration of CSF 5-HIAA in a suicide attempter is associated with a substantial increase in short-term suicide risk. CSF studies in violent criminals, and in nonhuman primates, suggest that aggression dyscontrol may partly explain the association between suicide and serotonin, which is of considerable theoretical interest. CSF 5-HIAA determinations may also be helpful in the clinical assessment of suicide risk.