Seminar Suicide and suicidal behaviour Gustavo Turecki, David A Brent Suicide is a complex public health problem of global importance. Suicidal behaviour differs between sexes, age groups, geographic regions, and sociopolitical settings, and variably associates with different risk factors, suggesting aetiological heterogeneity. Although there is no effective algorithm to predict suicide in clinical practice, improved recognition and understanding of clinical, psychological, sociological, and biological factors might help the detection of high-risk individuals and assist in treatment selection. Psychotherapeutic, pharmacological, or neuromodulatory treatments of mental disorders can often prevent suicidal behaviour; additionally, regular follow-up of people who attempt suicide by mental health services is key to prevent future suicidal behaviour. Introduction Suicide takes a staggering toll on global public health, with almost 1 million people dying from suicide worldwide each year.1 WHO has declared that reducing suicide-related mortality is a global imperative, a welcome contrast to the traditional taboo that has surrounded suicidal behaviours. Cultural and moral beliefs about suicide, and unnecessarily pessimistic views about treatment and prevention of suicide, are barriers to patient self-disclosure and clinicians’ routine inquiries about suicidal thoughts. About 45% of people who die by suicide consult a primary care physician within 1 month of death, yet documentation of physician inquiry or patient disclosure is rare.2 We review the epidemiology, risk factors, and effective interventions in primary care and specialty mental health facilities aimed at the prevention or treatment of suicidal behaviour. Definitions and assessment Clear discussion, accurate research, and efficient treatment require accepted definitions of suicidal behaviours. The difficulty of establishing intent of self-harming behaviours has hindered efforts to streamline the historically heterogeneous suicide nomenclature, but efforts, such as those resulting in the Columbia Classification Algorithm of Suicide Assessment,3 have contributed to standardising nomenclature (table). The severity of suicidal behaviour varies, on the basis of family studies showing the progression from less to more severe forms of suicidal ideation and behaviour, and from family and biological studies showing overlap between attempted and completed suicide.4 Epidemiology Precise global estimates of suicide rates are difficult to obtain, as only 35% of WHO member states have comprehensive vital registration with at least 5 years of data.1 Globally, an estimated 11·4 suicides per 100 000 people occur per year, resulting in 804 000 deaths.1 Suicide rates vary within and between countries, with as much as a ten-times difference between regions; this variation is partly correlated with economic status and cultural differences.1 Cultural influences might trump geographic location, because the suicide rates of immigrants are more closely correlated with their country www.thelancet.com Vol 387 March 19, 2016 of origin than with their adoptive country.5 Indigenous peoples have high rates of suicide,6 which might be caused by disruption of traditional cultural and family supports, lower socioeconomic status, and increased prevalence of alcohol and substance use, which are also risk factors for suicide in the general population.6 Non-fatal suicidal behaviours are more common than suicides.7,8 Data from 108 705 people included in the WHO World Mental Health Survey8 suggest that the average 12-month prevalence of ideation is 2·0% in high-income countries versus 2·1% in low-income countries, and the prevalence of suicide attempts is 0·3% versus 0·4%. The worldwide lifetime prevalence of ideation is 9·2% and that of attempts is 2·7%,9 but rates of ideation and suicidal behaviour vary greatly between countries (figure 1).1,9–12 Individuals who report suicide ideation within the previous 12 months have significantly higher 12-month prevalence rates of suicide attempts (15·1% in high-income countries and 20·2% in low-income countries), and suicidal planning further increases risk.7,8 Roughly a third of adolescents with suicide ideation will go on to attempt suicide within 1 year,7 and people who attempt suicide presenting to an emergency department have a 12-month risk of suicide of 1·6% and of repeated suicide attempt of 16·3%, with a 5-year risk of suicide of 3·9%.13 In high-income countries, suicide is most common among middle-aged and elderly men.1 However, rates of suicide in young people are increasing, and suicide is Lancet 2016; 387: 1227–39 Published Online September 16, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)00234-2 McGill Group for Suicide Studies, Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC, Canada (Prof G Turecki MD); and Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA (Prof D A Brent MD) Correspondence to: Prof Gustavo Turecki, McGill Group for Suicide Studies, Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC, Canada gustavo.turecki@mcgill.ca Search strategy and selection criteria The previous Lancet Seminar on suicide was published in 2009. We searched PubMed and the Cochrane Library from Jan 1, 2009, to May 30, 2015, with the terms suicide, suicidal behaviour, and self-harm along with category-specific terms, including epidemiology, genetics, intervention, prevention, and psychotherapy. Titles and abstracts of search results were read and sorted to assess inclusion of the article. We identified further articles by scanning the reference sections of selected publications. We primarily selected articles published in the past 6 years, but also included relevant and notable articles published before 2009. We selected only English language publications. For the 2009 Lancet Seminar on suicide see Lancet 2009; 373: 1372–81 1227 Seminar Definition Comments Suicide A fatal self-injurious act with some evidence of intent to die ·· Suicide attempt A potentially self-injurious behaviour associated with at least some intent to die Some younger people who attempt suicide report that their main motivation is other than to die, such as to escape an intolerable situation, to express hostility, or to get attention; however, many nonetheless acknowledge the possibility that their behaviour could have resulted in death; suicide attempt is characterised by greater functional impairment than non-suicidal self-injury Active suicide ideation Highly specific ideation, such as having made a plan or having intent, is associated Thoughts about taking action to end one’s life, including identifying a method, having a with a much greater risk of a suicide attempt within 12 months plan, or having intent to act Passive suicide ideation Thoughts about death or wanting to be dead ·· without any plan or intent Non-suicidal self-injury Self-injurious behaviour with no intent to die Differs from suicide attempt in terms of motivation, familial transmission (found only in suicidal behaviour), age of onset (younger in non-suicidal self-injury), psychopathology, and functional impairment (greater in suicide attempt); non-suicidal self-injury most commonly consists of repetitive cutting, rubbing, burning, or picking; the main motivations are either to relieve distress, to “feel something”, to induce self-punishment, to get attention, or to escape a difficult situation Suicidal events The onset or worsening of suicide ideation or Often used as an endpoint in pharmacological studies; rescue procedures are a suicide attempt, an emergency referral for included in this category because a patient with ideation who then received emergency intervention might have made an attempt had he or she not been ideation, or suicidal behaviour recognised and treated Preparatory acts toward ·· imminent suicidal behaviours ·· Deliberate self-harm The combination of suicide attempts and non-suicidal self-injury into one category reflects their high comorbidity, shared diathesis, and the fact that non-suicidal self-injury is a strong predictor of eventual suicide attempt; not all events classified as a suicide attempt are motivated by a true desire to die, but rather by desires to attract attention, to escape, and to communicate hostility; however, when only deliberate self-harm is reported, suicide attempts and non-suicidal self-injury cannot be subsequently disaggregated Any type of self-injurious behaviour, including suicide attempts and non-suicidal self-injury Suicidal ideation Suicide attempts Suicide deaths 16 14 12 10 8 6 4 a 13 0 re Ko ut h So 0 an 1 Jap in a1 nd 1 0 Ch ali a 12 ala Ze Ne w ric a 10 str Au 0 Af So ut h n 10 ria 1 ge no ba Le Ni l 10 ae e 10 in Isr 10 ra s 10 ain Uk Sp nd y 10 ly 10 er la Ne th Ita 0 an ce 1 rm Ge 10 um an Fr lgi Be 0 US A 10 ico 1 M ex bi m lo Ca Co na da 1 1 0 a 10 2 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 Prevalence of suicide deaths per 100 000 people Prevalence of non-fatal suicidal behaviour per 100 people Table: Nomenclature for suicidal and related behaviours and suicidal ideation Figure 1: National prevalences of suicidal behaviours Sources for data for non-fatal suicidal behaviours are cited in the figure; data for deaths from suicide are from the WHO 2014 report.1 the second leading cause of death in individuals aged 15–29 years.1 The incidence of suicide ideation and suicidal behaviour peaks in adolescents and young adults, with a lifetime prevalence of suicidal ideation of 12·1–33%, and of suicidal behaviour of 4·1–9·3%.7,14 In elderly people, rates of suicidality are also high, 1228 particularly among those with physical disorders, depression, and anxiety.15 Sex is also a factor in suicidal behaviour, with higher rates of ideation and suicide attempts among women;8,9 however, rates of suicide deaths are generally higher in men (15 per 100 000 men vs eight per 100 000 women, worldwide).1 The ratio of www.thelancet.com Vol 387 March 19, 2016 Seminar Population risk factors Lack of social cohesion Rapid changes in social structure or values Economic turmoil Social isolation Individual risk factors Distal or predisposing Developmental or mediating Proximal or precipitating Suicide Suicidal behaviour Family history Early-life adversity Cognitive deficits: impaired memory specificity and problem-solving Behavioural disinhibition High anxiety Epigenetic changes Development of personality traits High impulsive aggression Acute substance misuse Suicidal ideation Hopelessness Depressed mood Psychopathology* Genetics Stable changes in gene function Genetic and epigenetic factors Chronic substance use Biological, genetic, and epigenetic factors Life events Environmental factors Media reports Access to means Poor access to mental health care Figure 2: Model for suicide risk Suicide risk is modulated by a range of factors both at the population and individual levels. Individual risk factors can be grouped into distal (or predisposing), developmental (or mediating), and proximal (or precipitating) factors, and many of these factors interact to contribute to the risk of developing suicidal behaviours. *Any single mental illness associated with suicide risk, or a combination of mental illnesses, including major depressive disorder, bipolar disorder, schizophrenia, and personality disorders; the presence of a depressive episode is often a sign of increased risk of suicide. male to female deaths by suicide is higher in high-income countries (3·5) than in low-to-middle-income countries (1·6), and in Europe and the Americas (3·6–4·1) than in Asian Pacific countries (0·9–1·6).1 Seasonal variation in suicide rates has also been reported, with peak incidence in spring and summer, and suicide rates might correlate with latitude and exposure to sunshine.16 Contemporary models of suicide risk In the past century, the contributions of both social and individual factors to understanding suicide risk have been recognised. Several models have been proposed, most emphasising the interaction between predisposing and precipitating factors.17–20 Figure 2 shows putative temporal relationships between different suicide risk factors. Suicide has many causes, with substantial variability in the strengths and patterns of association of risk factors across sex, age, culture, geographic location, and personal history. Thus, models have been proposed to explain risks of suicide in specific subgroups, such as in people exposed to early-life adversity.21,22 www.thelancet.com Vol 387 March 19, 2016 Factors and associated mechanisms that increase risk of suicide Population-level risk factors More than a century ago, Durkheim recognised the effect of population-level social factors on suicide rates. Increases in suicide rates among indigenous peoples, such as Canadian Inuits, correlate with social changes such as forced settlement, assimilation, and disruption of traditional social structure.6 Conversely, suicide is rare in homogeneous societies with high social cohesion, common values, and moral objections to suicide,23,24 although the latter might also lead to under-reporting. Economic crises resulting in unemployment and decreased personal income have been correlated with increases in suicide, particularly in men, although a direct causal relationship has not yet been established.25,26 Media reporting of suicide also affects suicide rates, particularly within the first 30 days of publicity, with increases in the rate of suicide proportional to the amount of publicity, when details of a method are provided, if the decedent was a celebrity, and if the 1229 Seminar suicide was romanticised rather than reported in association with mental illness and the adverse consequences of the suicide on survivors.27 Adolescents and young adults are particularly susceptible to the effects of media publicity.28 Individual risk factors for suicide Distal or predisposing risk factors Suicidal behaviours run in families (odds ratio [OR] for first or second degree relatives is 1·7–10·62, when adjusting for degree of relation),4,29,30 indicating that distal factors can increase suicide risk. Family studies show that the risk of attempts is higher in relatives of people who died by suicide, and that the risk of dying by suicide is higher in relatives of people with a history of suicide attempts.31 These effects are unlikely to result from imitation because adoption studies show concordance between biological, but not adoptive relatives.32 Although psychopathological disorders also aggregate in families, the transmission of suicidal behaviour seems to be mediated through the transmission of impulsive aggression.4,33 Twin and adoption studies suggest that genetic factors account for part of the familial transmission of suicidal behaviour, with estimates of heritability of 30–50%.34,35 However, when the heritability of other psychiatric conditions is taken into account, the specific heritability of suicidality is estimated as 17·4% for suicide attempts and 36% for suicide ideation.35 Ideation seems to be cotransmitted with mood disorders and shows a distinct pattern for transmission from suicidal behaviour.4,36 Despite consistent evidence for the heritability of suicidal behaviour, the identification of specific genes associated with suicide risk remains elusive, despite several candidate-gene and genome-wide association studies, which have mostly provided inconclusive results.21 Modelling the interactions between experience and genes would be useful. In addition to heritable factors, other psychosocial, demographic, and biological factors increase vulnerability to suicide.17 Sexual orientation affects suicide risk, and although psychological autopsy-based studies of completed suicides have not consistently shown an over-representation of sexual minority status in people who die by suicide, analysis of registry-based data suggests that individuals with a history of same-sex relationships have a 3–4-times greater risk of dying by suicide, with a disproportionately greater risk for men than for women. Belonging to a sexual minority is universally linked with increased rates of suicide attempts irrespective of sex.37 Another well characterised risk factor is exposure to early-life adversity, generally defined as parental neglect or childhood physical, sexual, or emotional abuse. The association between early-life adversity and lifetime suicide risk is supported by evidence from prospective38,39 and retrospective longitudinal studies,40 as well as 1230 multiple case-control studies,22 and is moderated by several factors, including the type of abuse (neglect, physical abuse, or sexual abuse), the frequency of the abuse, and the relationship between the victim and the abuser.39 Early-life adversity might also be transmitted through families, partly explaining the familial aggregation of suicidal behaviour.41 Early-life adversity might induce long-term effects through epigenetic changes in gene pathways. The hypothalamic– pituitary–adrenal axis regulates physiological responses to stress to facilitate coping with changing environments or challenging events, mainly through cortisol regulation. Individuals who have experienced early-life adversity often have a hyperactive hypothalamic– pituitary–adrenal axis and an increased stress response,42 which is partly caused by decreased hippocampal expression of glucocorticoid receptors and is associated with increased DNA methylation of its promoter43 in both central nervous tissues and peripheral tissues such as blood or saliva.44 FKBP5 inhibits glucocorticoid receptor signal transduction and might contribute to the risk of suicidal behaviour; FKBP5 sequence variants are associated with an increased risk of suicidal behaviour, especially in people who have had early-life adversity.21 Early-life adversity is also associated with epigenetic modification of genes involved in neuronal plasticity, neuronal growth, and neuroprotection.45,46 Animal models of early-life adversity show hypermethylation and consequent downregulation of BDNF.47 Studies of brain tissue from people who completed suicide show that mRNAs encoding BDNF and its receptor TRKB are downregulated in several brain regions including the prefrontal cortex and the hippocampus, and some studies report differential methylation of BDNF and TRKB in the brains of people who died by suicide compared with in people who died from other causes.48,49 Genome-wide association studies of people with depression or people who have died by suicide and who had early-life adversity have identified methylation changes in genes associated with stress, cognitive processes, and neural plasticity.45,46 This evidence supports the hypothesis that early-life adversity mediates suicide risk through long-term epigenetic regulation of gene expression. Another potential risk factor for suicidal behaviour is infection with the brain-tropic parasite Toxoplasma gondii.50,51 In a large sample of women tested for T gondii infection at childbirth and followed up for more than a decade, seropositive women had increased risk of self-directed violence (OR 1·53, 95% CI 1·27–1·85), violent suicide attempt (1·81, 1·13–2·84), and suicide (2·05, 0·78–5·20), with risk of self-directed violence correlated with concentrations of anti-toxoplasma antibodies.50 One proposed mechanism for this association involves immunological responses to infection, which might alter neurotransmitter activity.52 www.thelancet.com Vol 387 March 19, 2016 Seminar Developmental or mediating r …


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