Kees van Heeringen

The neurobiology of suicide

The stress-diathesis model posits that suicide is the result of an interaction between state-dependent (environmental) stressors and a trait-like diathesis or susceptibility to suicidal behaviour, independent of psychiatric disorders. Findings from post-mortem studies of the brain and from genomic and in-vivo neuroimaging studies indicate a biological basis for this diathesis, indicating the importance of neurobiological screening and interventions, in addition to cognitive and mood interventions, in the prevention of suicide. Early-life adversity and epigenetic mechanisms might explain some of the link between suicide risk and brain circuitry and neurochemistry abnormalities. Results from a range of studies using diverse designs and post-mortem and in-vivo techniques show impairments of the serotonin neurotransmitter system and the hypothalamic-pituitary-adrenal axis stress-response system in the diathesis for suicidal behaviour. These impairments manifest as impaired cognitive control of mood, pessimism, reactive aggressive traits, impaired problem solving, over-reactivity to negative social signs, excessive emotional pain, and suicidal ideation, leading to suicidal behaviour. Biomarkers related to the diathesis might help to inform risk-assessment procedures and treatment choice in the prevention of suicide.

Suicide prevention strategies revisited: 10-year systematic review.

BACKGROUND Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. METHODS We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. FINDINGS We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. INTERPRETATION In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. FUNDING The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

The prevention and treatment of complicated grief: a meta-analysis.

BACKGROUND Bereaved individuals are at increased risk of mental and physical disorders, and prevention and treatment of complicated grief is indicated. Earlier quantitative reviews have not focused on the effect of bereavement interventions on (complicated) grief. Therefore the main objective of this meta-analysis was to determine the short-term and long-term effect of both preventive and treatment interventions on complicated grief. METHODS Randomized controlled trials for prevention or treatment of complicated grief were identified through a systematic literature search. Electronic databases and reference lists of earlier review articles served as data sources. Data were analyzed with REVMAN 5.0.14. RESULTS Fourteen randomized controlled trials met the inclusion criteria. Study quality differed among the trials. Contrary to preventive interventions, treatment interventions yielded significant pooled standardized mean differences in favor of the (specific) grief intervention at post-test and follow-up. During the follow-up period, the positive effect of treatment interventions for complicated grief even increased. CONCLUSIONS Treatment interventions can effectively diminish complicated grief symptoms. Preventive interventions, on the other hand, do not appear to be effective. Limitations of the meta-analysis and future research options are discussed.

Why people engage in parasuicide: a-cross-cultural study of Intentions.

Information obtained at interview from 1,646 parasuicide patients in 14 regions in 13 European countries participating in the WHO/EURO Multicentre Study on Suicidal Behaviour was used to study self-reported intentions involved in parasuicide. Comparisons were made across cultures, genders, and age groups. Although some statistically significant differences were found, the effect sizes were very small. The main finding from this study is thus that parasuicide patients in different countries tend to indicate that similar types of intentions are involved in their acts of parasuicide, and that the intentions do not vary greatly with gender or age. The hypothesis that rates of suicide and parasuicide vary between regions with the frequency with which suicidal intention is indicated by the patients was also tested, but was supported only for women and in relation to national suicide rates. The findings from this study are likely to be generalizable to other settings and have implications for clinical practice.

Reasons for adolescent deliberate self-harm: a cry of pain and/or a cry for help? Findings from the child and adolescent self-harm in Europe (CASE) study.

The present study examines reasons for adolescent deliberate self-harm. A cross-sectional survey using an anonymous self-report questionnaire was carried out in seven countries (Australia, Belgium, England, Hungary, Ireland, the Netherlands and Norway). Data on 30,477 school pupils between the ages of 14–17 were analysed. Past year and lifetime deliberate self-harm were assessed, along with the self-reported reasons for deliberate self-harm. The results showed that ‘wanted to get relief from a terrible state of mind’ and ‘wanted to die’ were most commonly reported. Principal component analysis indicated two underlying dimensions in the reasons for deliberate self-harm, i.e. a cry of pain motive and/or a cry for help motive. The majority of self-harmers reported at least one cry of pain motive (‘to die’, ‘to punish myself’, and ‘to get relief from a terrible state of mind’) and an additional cry for help motive (‘to show how desperate I was feeling’, to frighten someone’, ‘to get my own back on someone’, ‘to find out whether someone really loved me’, and ‘to get some attention’). Females reported more reasons than males. Only females showed an age difference, with girls aged 16–17 more frequently reporting a cry for help motive. There was considerable consistency in choice of motives across countries and genders. Systematic assessment of the reasons for deliberate self-harm can help clinicians to better understand the meaning of self harming behaviour, select appropriate treatment, suggest alternative coping strategies, and hopefully prevent future suicidal behaviour.

The Neurobiology of Suicide and Suicidality

Objective:To investigate the current state of knowledge regarding the neurobiology of suicide and suicidality.Method:The literature on the neurobiology of suicidality and suicide was reviewed.Results:There is clear evidence that the activity of 3 neurobiological systems has a role in the pathophysiology of suicidal behaviour. This includes hyperactivity of the hypothalamo-pituitary-adrenal axis, dysfunction of the serotonergic (5-HTergic) system, and excessive activity of the noradrenergic system. While the first and the last system appear to be involved in the response to stressful events, dysfunction of the serotonergic system is thought to be trait-dependent and associated with disturbances in the regulation of anxiety, impulsivity, and aggression. It can be hypothesized that neurobiological dysfunctions mediate the occurrence of suicidal behaviour through the disturbed modulation of basic neuropsychological functions.Conclusion:Increasing insight into the neurobiological basis of suicidal behaviour su...OBJECTIVE To investigate the current state of knowledge regarding the neurobiology of suicide and suicidality. METHOD The literature on the neurobiology of suicidality and suicide was reviewed. RESULTS There is clear evidence that the activity of 3 neurobiological systems has a role in the pathophysiology of suicidal behaviour. This includes hyperactivity of the hypothalamo-pituitary-adrenal axis, dysfunction of the serotonergic (5-HTergic) system, and excessive activity of the noradrenergic system. While the first and the last system appear to be involved in the response to stressful events, dysfunction of the serotonergic system is thought to be trait-dependent and associated with disturbances in the regulation of anxiety, impulsivity, and aggression. It can be hypothesized that neurobiological dysfunctions mediate the occurrence of suicidal behaviour through the disturbed modulation of basic neuropsychological functions. CONCLUSION Increasing insight into the neurobiological basis of suicidal behaviour suggests that serotonin (5-HT) agonists have an important role in the treatment and prevention of suicidal behaviour. Studies of the efficacy of such drugs have, however, been disappointing. Because suicidal behaviour continues to be a major public health problem, further study is clearly needed, including research on the effect of combined pharmacologic and psychotherapeutic approaches.

Deliberate self-harm in adolescents: comparison between those who receive help following self-harm and those who do not.

This international comparative study addresses differences between adolescents who engage in deliberate self-harm (DSH) and who receive help following the DSH episode versus those who do not. A standardised self-report questionnaire was completed by pupils aged 14-17 in Australia, Belgium, England, Hungary, Ireland, The Netherlands, and Norway (n=30,532). An act of DSH in the year prior to the study was reported by 1660 participants. Nearly half (48.4%) had not received any help following DSH, 32.8% had received help from their social network only and 18.8% from health services. Except for Hungary, cross-national comparisons revealed remarkably similar findings. Adolescents who had been in contact with health services following DSH reported more often a wish to die, lethal methods, alcohol/drug problems and DSH in the family compared to those who had not. However, those who received no help or help from their social network only were also heavily burdened.

Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity

BACKGROUND According to recent theories, suicidal behaviour is associated with depressive disorders that are commonly induced by social stressors in persons with a trait-dependent vulnerability. Stressor-induced increased cortisol secretion may interfere with this vulnerability that can be defined in terms of (possibly inter-related) biological and psychological or personality-related characteristics. Delineation of such trait-like characteristics may increase the specificity in the prediction of suicidal behaviour and thus lead to new approaches to the treatment and prevention of suicidal behaviour. METHODS Psychiatric symptomatology, personality dimensions (Cloningers Temperament and Character), peripheral markers of serotonergic (whole blood serotonin, platelet MAO activity) and noradrenergic (plasma MHPG) activity, and urinary cortisol were measured in a random sample of patients with a history of violent suicidal behaviour and compared to those of patients without such a history. RESULTS When compared to patients without a history of violent suicidal behaviour (n=23), patients with such a history (n=17) were characterised by higher urinary cortisol levels, a significantly lower mean score on Reward Dependence, a borderline significantly increased score on Novelty Seeking and a significantly lower mean plasma MHPG level. Urinary cortisol level correlated significantly with Reward Dependence and Novelty Seeking scores. There were no differences between patient groups regarding severity of anxiety or depressive symptomatology. No differences with regard to the biological parameters were found between patients who recently attempted suicide and those with a history of suicidal behaviour. LIMITATIONS Limitations of this study included a relatively small number of study subjects and the use of peripheral markers to assess central neurotransmission functions. CONCLUSIONS Violent suicidal behaviour is associated with increased cortisol secretion, a personality profile defined by low Reward Dependence (reflecting the degree of sensitivity to social stressors) and a tendency of increased Novelty Seeking (related to impulsivity and the regulation of anger), and reduced noradrenergic functioning (possibly reflecting an inability to adapt to stressors).

Suicide among adolescents : A psychological autopsy study of psychiatric, psychosocial and personality-related risk factors

BackgroundThe suicide rate among young males in Belgium has doubled over the last decade. As more knowledge about risk factors is required to develop national prevention strategies, we investigated adolescent suicides using the psychological autopsy method.MethodsA total of 32 informants were interviewed regarding 19 suicide cases (aged 15–19). A semi-structured interview schedule, constructed by Houston et al. (J Affect Disord 63:159–170, 2001), was used.ResultsAll adolescents were suffering from one or more mental disorder(s) at the time of their death, and almost half of them were diagnosed with personality disorders. Adjustment disorders were diagnosed in one fifth of the sample, which appears to be relevant in view of the multiple life events and other psychosocial problems which adolescents were facing shortly before death. This suggests that difficulties in coping with stressful psychosocial problems are important in the course of the suicidal process. Only a small minority was receiving treatment for their disorders.Conclusions Mental disorders, commonly untreated and combined with personality disorders and psychosocial problems, are frequently found in young suicide victims. This study suggests that education in the diagnosis and treatment of depression, adjustment disorders and suicide is important in the prevention of suicide.

Problem solving ability and repetition of deliberate self-harm: a multicentre study.

BACKGROUND While recent studies have found problem-solving impairments in individuals who engage in deliberate self-harm (DSH), few studies have examined repeaters and non-repeaters separately. The aim of the present study was to investigate whether specific types of problem-solving are associated with repeated DSH. METHOD As part of the WHO/EURO Multicentre Study on Suicidal Behaviour, 836 medically treated DSH patients (59% repeaters) from 12 European regions were interviewed using the European Parasuicide Study Interview Schedule (EPSIS II) approximately 1 year after their index episode. The Utrecht Coping List (UCL) assessed habitual responses to problems. RESULTS Factor analysis identified five dimensions--Active Handling, Passive-Avoidance, Problem Sharing, Palliative Reactions and Negative Expression. Passive-Avoidance--characterized by a pre-occupation with problems, feeling unable to do anything, worrying about the past and taking a gloomy view of the situation, a greater likelihood of giving in so as to avoid difficult situations, the tendency to resign oneself to the situation, and to try to avoid problems--was the problem-solving dimension most strongly associated with repetition, although this association was attenuated by self-esteem. CONCLUSIONS The outcomes of the study indicate that treatments for DSH patients with repeated episodes should include problem-solving interventions. The observed passivity and avoidance of problems (coupled with low self-esteem) associated with repetition suggests that intensive therapeutic input and follow-up are required for those with repeated DSH.