Jussi Jokinen

Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

Objective To assess the risk of attempted suicide before, during, and after treatment with isotretinoin for severe acne. Design Retrospective cohort study linking a named patient register of isotretinoin users (1980-9) to hospital discharge and cause of death registers (1980-2001). Setting Sweden, 1980-2001. Population 5756 patients aged 15 to 49 years prescribed isotretinoin for severe acne observed for 17 197 person years before, 2905 person years during, and 87 120 person years after treatment. Main outcome measures Standardised incidence ratio (observed number divided by expected number of suicide attempts standardised by sex, age, and calendar year), calculated up to three years before, during, and up to 15 years after end of treatment. Results 128 patients were admitted to hospital for attempted suicide. During the year before treatment, the standardised incidence ratio for attempted suicide was raised: 1.57 (95% confidence interval 0.86 to 2.63) for all (including repeat) attempts and 1.36 (0.65 to 2.50) counting only first attempts. The standardised incidence ratio during and up to six months after treatment was 1.78 (1.04 to 2.85) for all attempts and 1.93 (1.08 to 3.18) for first attempts. Three years after treatment stopped, the observed number of attempts was close to the expected number and remained so during the 15 years of follow-up: standardised incidence ratio 1.04 (0.74 to 1.43) for all attempts and 0.97 (0.64 to 1.40) for first attempts. Twelve (38%) of 32 patients who made their first suicide attempt before treatment made a new attempt or committed suicide thereafter. In contrast, 10 (71%) of the 14 who made their first suicide attempt within six months after treatment stopped made a new attempt or committed suicide during follow-up (two sample test of proportions, P=0.034). The number needed to harm was 2300 new six month treatments per year for one additional first suicide attempt to occur and 5000 per year for one additional repeat attempt. Conclusions An increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin, which motivates a close monitoring of patients for suicidal behaviour for up to a year after treatment has ended. However, the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established. As patients with a history of suicide attempts before treatment made new attempts to a lesser extent than did patients who started such behaviour in connection with treatment, patients with severe acne should not automatically have isotretinoin treatment withheld because of a history of attempted suicide.

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.

HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients.

BACKGROUND Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. METHODS The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. RESULTS The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. CONCLUSIONS The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

HPA axis hyperactivity and cardiovascular mortality in mood disorder inpatients

Depression is associated with an increased risk of cardiovascular disease (CVD), coronary heart disease (CHD) and cardiac death. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is frequent in major depression and hypercortisolemia may be a mediating factor in these relationships. The aim of this study was to assess HPA axis function measured with the dexamethasone suppression test (DST) in relation to CVD and CHD mortality in a cohort of 382 inpatients with mood disorder admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. Death certificates ascertained that 75 patients had died of cardiovascular disease and 30 patients of CHD during the mean follow-up of 18 years. DST non-suppression and higher baseline serum cortisol predicted CVD death. In male inpatients with mood disorder, the DST non-suppressor status was significantly associated with CVD death but not with CHD death. In depressed female inpatients the DST non-suppression was not associated with cardiovascular mortality. Baseline serum cortisol and post-dexamethasone serum cortisol levels at 4:00 p.m. showed a trend to be higher in female CVD/CHD victims. Effect of aging on HPA axis functioning was shown in male CHD deaths. HPA axis dysregulation may be a mediating factor between depression and increased risk of cardiovascular death in male mood disorder inpatients indicating that HPA-axis hyperactivity is a long term risk factor for cardiovascular mortality.

Suicide Intent Scale in the prediction of suicide

OBJECTIVE To assess the predictive value of the Suicide Intent Scale in patients with high suicide risk. The secondary aim was to assess if the use of the factors of the Suicide Intent Scale may offer a better predictive value in suicide risk detection. Finally a shorter version of the scale was created after an item analysis. METHOD Eighty-one suicide attempters were assessed with the Becks Suicide Intent Scale (SIS). All patients were followed up for cause of death. Receiver-operating characteristic (ROC) curves and tables were created to establish the optimal cut-off values for SIS and SIS factors to predict suicide. RESULTS Seven patients committed suicide during a mean follow up of 9.5 years. The major finding was that mean SIS scores distinguished between suicides and survivors. The positive predictive value was 16.7% and the Area Under Curve (AUC) was 0.74. Only the planning subscale reached statistical significance. Four items were used to test a shorter version of the SIS in the suicide prediction. The positive predictive value was 19% and the AUC was 0.82. CONCLUSIONS The Suicide Intent Scale is a valuable tool in clinical suicide risk assessment, a shorter version of the scale may offer a better predictive value.

Suicide in schizophrenia

Schizophrenia is a disorder with an estimated suicide risk of 4–5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.

HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide

Abstract Objectives. Immunological differences have previously been associated with depression and suicidal behaviour. Several cytokines have been identified as potentially important in understanding the pathophysiology of mood disorders and suicidality. Here we aimed to identify new inflammatory biomarkers for suicide prediction. Methods. Plasma concentrations of interleukin (IL) 1-a , IL1-b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFNG), tumor necrosis factor-a (TNF-a), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) were measured in 58 suicide attempters with a high throughput automated biochip immunoassay system. Patients were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Suicide Intent Scale (SIS). All patients were followed up for cause of death. Results. We found significantly lower levels of VEGF in the seven patients who upon a mean follow-up of 13 years were found to have completed suicide. VEGF also showed a trend for negative correlation with the planning subscale of SIS. A trend could be shown for lower IL-2 and for higher IFNG levels in suicide victims. Conclusions. Our study provides further support for a role of inflammation in the pathophysiology of suicidality. VEGF may be related with suicide risk.

Cholesterol and CSF 5-HIAA in attempted suicide

BACKGROUND Low serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans. AIM To study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity. METHODS Serum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Beckss Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery-Asberg depression rating scale (MADRS) and followed-up for causes of death. RESULTS Serum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors. CONCLUSIONS These findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt.

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.