The Impact of Upcoming Treatments in Huntington's Disease: Resource Capacity Limitations and Access to Care Implications.

BACKGROUND: The most advanced disease-modifying therapies (DMTs) in development for Huntington's disease (HD) require intrathecal (IT) administration, which may create or exacerbate bottlenecks in resource capacity. OBJECTIVE: To understand the readiness of healthcare systems for intrathecally administered HD DMTs in terms of resource capacity dynamics and implications for patients' access to treatment. METHODS: Forty HD centres across 12 countries were included. Qualitative and quantitative data on current capacity in HD centres and anticipated capacity needs following availability of a DMT were gathered via interviews with healthcare professionals (HCPs). Data modelling was used to estimate the current capacity gap in HD centres. RESULTS: From interviews with 218 HCPs, 25% of HD centres are estimated to have the three components required for IT administration (proceduralists, nurses and facilities). On average, 114 patients per centre per year are anticipated to receive intrathecally administered DMTs in the future. At current capacity, six of the sampled centres are estimated to be able to deliver DMTs to all the anticipated patients based on current resources. The estimated waiting time for IT administration at current capacity will average 60 months (5 years) by the second year after DMT availability. CONCLUSION: Additional resources are needed in HD centres for future DMTs to be accessible to all anticipated patients. Timely collaboration by the HD community will be needed to address capacity gaps. Healthcare policymakers and payers will need to address costs and navigate challenges arising from country- or region-specific healthcare delivery schemes.

Exposure to interpersonal violence and risk of post-traumatic stress disorder among women with borderline personality disorder.

BACKGROUND: This study aims to determine the validity of the Karolinska Interpersonal Violence Scale (KIVS), as a screening tool for PTSD, among women with borderline personality disorder (BPD) and severe suicidal behavior. METHOD: 106 women with BPD and at least two suicide attempts were assessed with the KIVS for exposure to interpersonal violence as a child and as an adult. The screening ability of the KIVS for the diagnosis of PTSD was analyzed using receiver operating characteristic curve analysis. RESULTS: PTSD diagnosis was valid for 61 (58%) women with BPD. The KIVS - exposure of lifetime interpersonal violence, displayed fair accuracy of predicting diagnosis of PTSD (area under the curve 0.79, confidence interval [0.71, 0.88]) and performed well (sensitivity 0.90 and specificity 0.62), with a cut-off score of 4 (range 0-10). Poly-traumatization was not significantly related to PTSD diagnosis as compared to single traumatization, whereas sexual victimization was significantly more prevalent in women with PTSD diagnosis, as compared to other types of traumatic events. CONCLUSION: A score of 4 or more on the KIVS - exposure to interpersonal lifetime violence presents well as a screening instrument for risk of PTSD, among women with BPD.

CSF Apolipoprotein E in attempted suicide.

BACKGROUND: Cholesterol and cholesterol metabolism, involved in continued neural plasticity, has been associated to suicide and suicidal behavior. Apolipoprotein E (ApoE) plays an important role in the cholesterol metabolism. The purpose of this study was to investigate whether ApoE in cerebrospinal fluid was related to severity of suicidal behavior as measured by number of earlier suicide attempts, reversibility/interruptabilty and violent method of suicide attempt. METHODS: CSF ApoE and 5-hydroxyindolacetic acid (5-HIAA) were measured in 42 medication free suicide attempters. Earlier suicide attempts and the reversibility of suicide attempt method were assessed with the Suicide Intent Scale (SIS) and the Freeman Scale. Suicide attempts were classified according to violence of method. RESULTS: CSF ApoE levels significantly negatively correlated to the scores on Freeman Reversibility and there was a trend for lower CSF ApoE levels in suicide attempters using a violent method. Patients with at least one earlier suicide attempt (repeaters) showed a trend for higher CSF ApoE levels compared to suicide attempters debuting with suicidal behavior at inclusion in the study. The correlation between CSF ApoE and 5-HIAA was not significant. LIMITATIONS: The main limitations to this study were a relatively small sample size and lack of a healthy control group. CONCLUSION: Irreversible suicide attempts, representing a high risk for completed suicide, may be associated with lower level of ApoE in CSF.

Plasma apolipoprotein E and severity of suicidal behaviour.

There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthermore, hypothalamic-pituitary-adrenal (HPA) axis function, one of the main biological systems implicated in both suicidal behaviour and early-life adversity, affect ApoE levels. Very few studies have assessed plasma ApoE in relation to suicidal behaviour. The purpose of this study was to investigate levels of ApoE in plasma in relation to the severity of suicidal behaviour and life-time adversity in the form of exposure to interpersonal violence in suicide attempters. A total of 100 suicide attempters (67 women and 33 men) were enroled in the study. Information on earlier suicide attempts and age at onset of suicidal behaviour was gathered using the Karolinska Suicide History Interview. The Karolinska Interpersonal Violence Scale was used to assess exposure to interpersonal violence. Plasma ApoE was measured by immunonephelometry according to accredited routines. Patients with at least one earlier suicide attempt had significantly higher ApoE levels compared to suicide attempters debuting with suicidal behaviour at inclusion in the study. A higher number of earlier suicide attempts was significantly correlated with higher plasma ApoE levels. Age at onset was significantly negatively correlated with ApoE after adjusting for age. ApoE showed a significant positive correlation with exposure to interpersonal violence as a child in male suicide attempters. Our findings indicate that ApoE may be related to stress and trauma and the temporal severity of suicidal behaviour.

Thyroid hormones and adult interpersonal violence among women with borderline personality disorder.

Elevated T3 levels have been reported in men with antisocial behavior. The aim of the present study was to investigate the relationship between thyroid hormones and expressed adult interpersonal violence in female patients with borderline personality disorder (BPD). Furthermore, expressed adult interpersonal violence in female BPD patients was compared to healthy female controls. A total of 92 clinically euthyroid women with BPD and 57 healthy women were assessed with the Karolinska Interpersonal Violence Scales (KIVS). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays in patients. Plasma cortisol was also measured. Among females with BPD, expressed interpersonal violence as an adult showed a significant positive correlation with the T3 levels. The mean expression of interpersonal violence as an adult was significantly higher in BPD patients as compared to healthy controls. The multiple regression model indicated that two independent predictors of KIVS expressed interpersonal violence as an adult: T3 and comorbid diagnosis of alcohol abuse. Association between T3 levels and violent/aggressive behavior earlier reported exclusively in male samples may be valid also in females with BPD.

Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.

Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 µg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders.

Hypothalamic pituitary thyroid axis and exposure to interpersonal violence in childhood among women with borderline personality disorder.

BACKGROUND: A relationship between exposure to sexual violence and thyroid hormone alterations has been observed among women with posttraumatic stress disorder (PTSD). Women with borderline personality disorder (BPD) report a high estimate of childhood trauma. OBJECTIVE: The aim of the present study was to assess relationships between thyroid hormone measures and exposure to violence in childhood in women with BPD. METHOD: A total of 92 clinically euthyroid women with BPD (53% with comorbid PTSD) diagnosis and at least two prior suicide attempts were assessed with the Karolinska Interpersonal Violence Scales (KIVS). The KIVS contains four subscales with concrete examples of exposure to violence and expressed violent behavior in childhood (aged 6-14 years) and during adult life (15 years or older). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays. The FT3/FT4 ratio was used to estimate peripheral deiodination. Plasma cortisol was also assessed. RESULTS: Sixty-seven percent of patients reported medium high or high level of exposure to interpersonal violence as a child. The FT3/FT4 ratio showed a significant negative correlation with exposure to violence as a child. Patients with PTSD had significantly higher plasma cortisol levels. An ad hoc analysis revealed that the correlation between KIVS exposure to interpersonal violence as a child and FT3/FT4 ratio was significant only in patients with comorbid PTSD. Altered thyroid activity, especially FT3/FT4, levels was associated with exposure to violence in childhood in women with BPD. CONCLUSION: Severe childhood trauma-related stress may promote lasting altered thyroid levels and/or contribute to the development of psychopathology associated with BPD traits or PTSD.

Cholesterol and the "Cycle of Violence" in attempted suicide.

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

Reduced ADHD symptoms in adults with ADHD after structured skills training group: results from a randomized controlled trial.

OBJECTIVE: Feasibility, acceptability, and efficacy of a Dialectical Behavioral Therapy (DBT) -based method developed in Germany were evaluated in a Swedish outpatient psychiatric context. METHOD: Fifty-one adults with ADHD on stable medical treatment or on no medication were randomized to the DBT-based skills training (n=26) or a parallel loosely structured discussion group (n=25). Self-rating scales were administered before randomization and after the treatment. RESULTS: Feasibility and participant satisfaction were good in both groups while skills training was perceived as more logical and effective for ADHD-related problems. The analyses of the individuals who completed the treatment and remained stable with regard to medication (n=19 in skills training; n=18 in control group) showed a significant reduction in ADHD symptoms in the skills training group, but not in the control group. No reduction of comorbidity was observed in any of the groups. CONCLUSIONS: The treatment was feasible in an outpatient psychiatric context, well tolerated, and significantly reduced ADHD symptoms in on-treatment individuals who remained stable regarding medication status.

Early death and CSF monoamine metabolites in schizophrenia spectrum psychosis.

INTRODUCTION: Patients with schizophrenia have higher rates of mortality than the general population. Lower concentrations of the cerebrospinal fluid (CSF) monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) have been associated with suicidal, aggressive and impulsive behavior. Mortality has been suggested as a measure of impulsivity and a relationship between early death and lower concentrations of CSF monoamine metabolites has been reported but the studies are few with short periods of follow-up and small numbers. AIM: The objective of this study was to investigate a relationship between early death and concentrations of CSF 5-HIAA and HVA. METHODS: Three hundred and eighty-five inpatients with schizophrenia spectrum psychosis were lumbar punctured in a standardized manner and followed for a median of 26 years. Patients were searched to identify those who had died. Causes of death were obtained from the Causes of Death Register. RESULTS: During the time of follow-up, 97 patients died. Schizophrenia spectrum psychosis patients died at an earlier age from both natural and unnatural causes of death. No significant associations were found between CSF 5-HIAA and HVA concentrations and non-suicidal death. Attempted suicide was not a risk factor for non-suicidal death at younger age. CONCLUSION: Patients with schizophrenia spectrum psychosis die at an earlier age from both natural and unnatural causes of death. Attempted suicide is not a risk factor for non-suicidal death at younger age. Low concentrations of CSF HVA and 5-HIAA were not a risk factor for non-suicidal death at younger age in schizophrenia spectrum psychosis.

Deficient cardiovascular stress reactivity predicts poor executive functions in adults with attention-deficit/hyperactivity disorder.

Associations between cardiovascular stress markers, subjective stress reactivity, and executive functions were studied in 60 adults (30 with attention-deficit/hyperactivity disorder, ADHD, and 30 controls) using the Paced Auditory Serial Addition Test (PASAT, a test of executive functions) as a cognitive stressor. Despite higher self-perceived stress, the adults with ADHD showed lower or atypical cardiovascular stress reactivity, which was associated with poorer performance on PASAT. Using cardiovascular stress markers, subjective stress, and results on PASAT as predictors in a logistic regression, 83.3% of the ADHD group and 86.9% of the controls could be classified correctly.

Cholesterol, CSF 5-HIAA, violence and intent in suicidal men.

Associations between suicide, violent behaviour and both hypocholesterolaemia and low 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been suggested. The relationships between lipids, the serotonergic system, suicidal and aggressive behaviors are complex. We explored relationships between serum cholesterol, CSF 5-HIAA, the planning subscale of suicide intent and violence of attempted suicide method in 13 medication-free male suicide attempters and eight healthy volunteers. Serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in suicide attempters than in controls. HDL-C showed a significant positive correlation with the planning subscale of suicide intent in non-violent suicide attempters. A positive association was observed between CSF 5-HIAA and serum cholesterol in suicides. The role of cholesterol may be different in planned non-violent suicide attempts compared with violent suicide attempts.

Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis.

BACKGROUND: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor. AIM: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide. METHOD: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records. RESULTS: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters. CONCLUSION: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.

Suicide risk after homicide in Sweden.

Temporal aspects of suicide risk after homicide using survival analytic method are not fully known and the risk estimates are almost exclusively based on studies of less than 10 years of follow-up. We investigated a population based cohort of 167 Swedish homicide offenders from 1970 to 1980 for which causes of death during the following minimum of 22 years were investigated using survival analysis. Twenty nine suicides (17.4%) occurred during the follow-up representing 30% of the total mortality. A high proportion of suicides (72%) occurred early, within 2 years after the homicide. The suicides continued to accumulate during the following decades after the homicide and the cumulative suicide risk was 18.6%. A very high proportion of violent suicide method (86%) was found. Suicide mortality was heavily skewed towards the first years after the homicide. Homicide offenders have very high short term suicide risk and the suicide risk persists over the entire adult lifespan. Homicide is a strong predictor of future suicide and similar biological mechanisms may be involved in violent criminality and suicidal behavior.

Thyroid hormones and personality traits in attempted suicide.

The research on thyroid hormones and personality traits is quite sparse and mainly focused on male forensic psychiatric populations in which the relationship between thyroid hormones and psychopathy and aggression-related personality traits has been reported. The suicidal temperament hypothesis suggests that certain personality traits such as aggression, anxiety proneness, impulsivity, and low socialization may render an individual vulnerable to the risk of suicide. The aim of this study was to investigate personality traits assessed by the Karolinska Scales of Personality (KSP) in relation to hormones in the hypothalamic-pituitary-thyroid (HPT) axis in 100 euthyroid suicide attempters. Standard multiple regression analyses were performed with TSH, T3, T4, and the T3/T4 ratio, respectively, as the dependent variable and KSP factors (Anxiety Proneness, Aggressiveness, and Impulsivity) and subscales (Detachment, Social Desirability, and Socialization) as independent variables. In men, but not in women, the regression model of the T3/T4 ratio was significant and the results suggested that high scores on Aggressiveness and low ones on Detachment were associated with a low T3/T4 ratio. These results indicate that HPT function may be related to Aggressiveness and Detachment in male suicide attempters.

CSF 5-HIAA, attempted suicide and suicide risk in schizophrenia spectrum psychosis.

INTRODUCTION: There is evidence for a relationship between low levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and suicidal behavior in mood disorder. A relationship between CSF homovanillic acid (HVA) and suicidal behavior has not been completely established. Studies done in patients with schizophrenia spectrum psychosis suffer from small numbers, short periods of follow-up and the results are contradictory. The objective of this study was to investigate the relationship between levels of CSF 5-HIAA, CSF HVA and suicidal behavior in patients with schizophrenia spectrum psychosis. METHOD: Three hundred eighty five patients with schizophrenia spectrum psychosis admitted to the Karolinska University Hospital between 1973 and 1987 were lumbar punctured in standardized manner. Patients were followed until 2006 for a median of 26 years. Information about prior suicide attempt was retrieved from medical records and causes of death were obtained from the Causes of Death Register at the National Board of Health and Welfare. RESULTS: At the end of the follow-up 26 patients (6.8%) had died by suicide. Male gender (OR=3.5) and attempted suicide (OR=12.4) were risk factor for suicide when combined. There were no significant correlations between levels of CSF 5-HIAA, CSF HVA, HVA/5-HIAA ratio and attempted, violent or non-violent suicide. CONCLUSION: Male schizophrenia spectrum psychosis patients with prior suicide attempt are at high risk for suicide. No correlation between CSF monoamine metabolites levels and suicidal behavior was found. Suicidal behavior in schizophrenia spectrum psychosis may not, in contrast to mood disorders, be predicted by levels of CSF 5-HIAA and HVA.

Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans.

The human serotonin transporter (5-HTT) gene is one of the most extensively studied in psychiatry. A functional polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR) has been associated with several psychiatric disorders as well as anxiety-related personality traits. In search of a mechanistic understanding of the functional implications of 5-HTTLPR, the influence of this polymorphism on regional 5-HT1A receptor density has previously been examined in two positron emission tomography (PET) studies in humans, yielding, however, contradictory results. In the present study, 54 control subjects were examined with [11C]WAY 100635 PET and a battery of cognitive tests. Regional binding potential (BP) of [11C]WAY 100635 to 5-HT1A receptor was calculated for the dorsal raphe nuclei, the hippocampus, the anterior cingulate, the insula, the temporal cortex and the frontal cortex. The influence of 5-HTTLPR genotype on regional 5-HT1A BP and cognitive performance was investigated. No differences in 5-HT1A receptor density between carriers and non-carriers of the S allele were found. Thus, we could not replicate any of the previously reported associations between 5-HTTLPR and 5-HT1A density. There was, however, a highly significant association between 5-HTTLPR genotype and performance in Wisconsin Card Sorting Test; carriers of the S allele had a superior performance compared to the LL carriers. These observations suggest that functional implications of the 5-HTTLPR polymorphism are not likely to be mediated by differences in 5-HT1A expression levels and that other biomarkers must be considered for future investigations at phenotype level.

5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women examined with [(11)C] WAY100635 and [(11)C] MADAM PET.

The aim of the present study was to explore the effects of the menstrual cycle phases on 5-HT(1A) receptor and 5-HTT binding potentials (BPs) in healthy women by using positron emission tomography (PET). Women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [(11)C]WAY10035 (n=13) and [(11)C]MADAM (n=8) to study 5-HT(1A) and 5-HTT BPs. The BPs values were quantified using the simplified reference tissue model. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV) and plasma levels of hormones estradiol (E(2)), progesterone (P(4)), follicle stimulating hormone (FSH) and luteinizing hormone (LH).The 5-HT(1A) receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between the change in E(2) or P(4) values with the change in 5-HT(1A) receptor or 5-HTT BPs. The results provide principally a new in vivo finding in human female biology, suggesting the absence of influence of menstrual cycle phase on 5-HT(1A) receptors or 5-HTT. The finding however does not preclude that gonadal hormones differentially influence central serotonin system inwomen and men, which might contribute to gender differences in serotonin-associated disorders.

High self-perceived stress and many stressors, but normal diurnal cortisol rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder).

Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with significant impairment in many life activities and may thus increase the risk of chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis (n=28) with healthy controls (n=28) regarding subjective stress and amounts of stressors in everyday life, diurnal salivary cortisol in the everyday environment and salivary cortisol before and after cognitive stress in a laboratory setting. The association between cortisol concentrations and impulsivity was also investigated. Consistent with assumptions, individuals with ADHD reported significantly more self-perceived stress than controls, and subjective stress correlated with the amount of stressors in everyday life. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm, as well as in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not baseline cortisol) concentration was positively correlated with impulsivity. The group with high post-stress cortisol also reported more symptoms of depression and anxiety, as well as self-perceived stress and stressors in every-day life. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The results in this study warrant a focus not only on the primary diagnosis of ADHD, but also calls for a broader assessment of stressors and subjective stress in everyday life, as well as support comprising stress management and coping skills.

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.