Guest Editorial
Suicide: The Persisting Challenge
Isaac Sakinofsky, MB, ChB, DPM, MD, FRCPC, FRCPsych1
In Canada, 4074 persons took their lives in 1999, the latest year for which suicide data are available. This equates with age-standardized death rates of 21 and 5 per 100 000 for males and females, respectively, and of 13 per 100 000 for the sexes combined. Suicide remains a grave problem in this country; it burgeoned during the late 1960s and 1970s, peaked in the early 1980s, and plateaued just below its peak during the 1990s. Although female suicide rates have decreased, suicide stubbornly remains at this level for males (who comprise four-fifths of suicides) (Figure 1). Contrast this with Scandinavian countries such as Sweden, where suicide rates decreased 28% between 1991 and 1997 in parallel with the increased use of antidepressants. In no demographic subgroup in Sweden did suicide rates fall without a corresponding increase in the use of antidepressants. Further, this decrease was not apparently related to changes in unemployment rates or alcohol misuse (1,2). The inverse relation between suicide rates and antidepressant use was also seen over this period in 3 other Nordic countries. However, suicide rates did not decrease in women under age 30 years or over age 75 years, despite increased antidepressant use. Whether the association between the expanding use of antidepressant drugs and the fall in suicide rates in some Scandinavian demographic groups is directly causal may well be debated, but as one who was a medical student before there were any antidepressants, I have no doubt that these drugs have been of overall benefit to those with mental illness.
As in most Western countries, the increased use of antidepressant drugs in Scandinavia arises from the availability of new generations of selective serotonin reuptake inhibitors (SSRIs), selective noradrenalin reuptake inhibitors (SNRIs), and beyond, which offer relative safety in overdose and a more tolerable side effect profile than did the older tricyclics and their metabolites. The newer drugs were designed following remarkable discoveries made mainly by Swedish and American biological researchers but also by researchers from other countries. These discoveries initially pointed to a lesion in the serotonergic system and now also implicate other neurotransmitter systems (3,4). Most of the research in humans was done with depression patients, and suicide and suicide attempts were important outcome measures (5,6); studies of central brain neurotransmitters and receptors relied on a brain bank of suicide victims and control subjects (7). Therefore, although the primary aim of such research was to understand depressive illness, the result has also included considerable growth in our knowledge of the neurobiological basis of suicide and suicide attempts. Other researchers have since extrapolated these findings dimensionally to suicidal behaviour in nonmood disorders, such as schizophrenia (8,9) and personality disorder (10,11). Several research centres nowadays focus their work on increasing our understanding of the neurobiology of suicide.
This issue’s In Review section features 2 papers that I have invited, as guest editor. The first, “The Neurobiology of Suicide and Suicidality” (12), is by a distinguished European researcher, Prof Kees Van Heeringen, of the University of Gent. In this paper, Dr Van Heeringen, who is also joint editor of an international reference work on suicide (13), expounds his model of the “suicidal process”—the theme of his recent edited volume, Understanding Suicidal Behaviour: The Suicidal Process Approach to Research, Treatment and Prevention (14). According to this concept, suicidality is a process that develops over time and is largely independent of specific psychiatric states but gives expression to trait-like propensities within individuals that control their interaction with social surroundings. This concept overlaps with and incorporates the stress–diathesis model of Mann and colleagues (15). However, the process model emphasizes both sides of the mind–body coin, the psychological and the biological. In the psychological aspect, past events may have sensitized individuals to see themselves as failures, to anticipate defeat when confronted by a stressor, and to feel trapped and without means of rescue. Insofar as the neurobiological side of the coin is concerned, Van Heeringen implicates 3 biological systems: overactivity of the hypothalamic-pituitary-adrenal axis, serotonergic dysfunction, and hyperfunction of the noradrenergic system.
Figure 1 Age-standardized suicide rates in Canada 1950–1999 (logarithmic).
Data source: Statistics Canada
Genetic influences in suicidal trait formation are also being given more importance. Statham and colleagues conducted telephone interviews with 6000 respondents from the Australian twin register and found that, after adjustment for other risk factors, a history of persistent suicidal ideation or attempts predicted suicidality with an odds ratio of 4 in monozygotic, but not dizygotic, cotwins. Genetic influences were estimated to account for 45% of the variance in this study (16). Though promising, the international pursuit for a “suicide gene” or genes has not, however, so far borne fruit (17). As-yet-unknown genetic variants mediate intermediate phenotypes such as impulsivity and aggression, which are normally modulated by the serotonergic system (4). Neuroimaging studies using positron emission tomography (PET) have pinpointed regional brain activity involving such phenotypes to the ventral, medial, and lateral prefrontal cortex. In one such study, depression patients with histories of high- and low-lethality suicide attempts were scanned following fenfluramine challenges. The high-lethality attempters had lower regional cerebral glucose uptake in the above areas, relative to the low-lethality attempters, and they also had histories of lower lifetime impulsivity and higher suicidal intent (planning) (18).
This intriguing PET study is complemented by a recent Toronto investigation that looked at the relation between dysfunctional attitudes (negatively biased assumptions and beliefs—rather like those of defeat, entrapment, and hopelessness referred to above) and serotonergic activity (measured by cortex 5-HT2 receptor binding potential) (19). The subjects were groups of healthy volunteers; patients with an episode of major depression and no history of suicidality outside such episodes; and patients with borderline personality disorder, chronic suicidal ideation, and potentially lethal self-harm behaviour. Comorbid depressive illness was not an exclusion criterion, provided that there was a history of self-harm outside depressive episodes. As in the first PET study, regional brain activity was found to be concentrated in the prefrontal cortex (Brodmann’s area 9), but otherwise, the results were surprising. As hypothesized and in line with current opinion, a single dose of fenfluramine was indeed associated with decreased scores on the Dysfunctional Attitudes Scale (DAS) in the healthy volunteers, and the patients with major depressive disorder showed a positive correlation between their dysfunctional attitudes and 5-HT2 receptor binding potential (indicating a positive relation between greater dysfunctional attitudes and serotonergic depletion). However, the upset to current opinion was that the suicidal borderline personality patients showed no such association (19). These results raise important questions regarding the putative unidimensionality of suicidality and the basis of the differences found between the suicidal patients with depression and the chronically suicidal patients with borderline personality.
Against this backdrop, the second paper (20), which deals with Cluster B personality disorders, is extremely relevant. It is also relevant because, in clinical practice, underlying personality disorders often contribute strongly to antidepressant treatment-resistance in suicidal patients with depressive illness. The lead author, Dr Paul Links, is the first incumbent of the Arthur Sommer Rotenberg Chair in Suicide Studies at the University of Toronto; he has published extensively on borderline personality disorders. Dr Links and his colleagues focus primarily on young persons, but the same principles can be applied to older age groups as well. The authors warn of the high suicide risk among such patients, particularly if compounded by Axis I comorbid disorder, and offer a clinical approach to dealing with this very difficult, time-consuming, and patience-testing clientele. Elsewhere, Paris has recently commented (21) on the guidelines for treatment of borderline personality disorders published by the American Psychiatric Association and pointed to the gap in evidence-based data that retards support for a broad consensus on treatment. The paper by Links and colleagues should prove helpful to clinicians, even though more research is needed to strengthen clinicians’ confidence in how they are treating such patients. One of the paper’s strengths is its focus on careful evaluation and assessment, which has also been stressed recently by others working in this area (11,22).
References
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8. van Praag HM. (Auto)aggression and CSF 5-HIAA in depression and schizophrenia. Psychopharmacol Bull 1986;22;669–73.
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10. Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, and others. Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry 1982;139:741–6.
11. Trull TJ, Stepp SD, Durrett CA. Research on borderline personality disorder: an update. Curr Opin Psychiatry 2003;16:77–82.
12. Van Heeringen K. The neurobiology of suicide and suicidality. Can J Psychiatry 2003;48:292–300.
13. Hawton K, Van Heeringen K. The international handbook of suicide and attempted suicide. Chichester (UK): John Wiley and Sons; 2000.
14. Van Heeringen K. Understanding suicidal behaviour: the suicidal process approach to research, treatment and prevention. Chichester (UK): John Wiley and Sons; 2001.
15. Mann JJ, Waternaux C, Haas GL, Malone KM. Toward a clinical model of suicidal behaviour in psychiatric patients. Am J Psychiatry 1999;156:181–9.
16. Statham DJ, Heath AC, Madden PAF, Bucholz KK, Bierut L, Dinwiddie SH, and others. Suicidal behavior: an epidemiological and genetic study. Psychol Med 1998;28:839–55.
17. Turecki G. Suicidal behavior: is there a genetic predisposition? Bipolar Disorder 2002;3:335–49.
18. Oquendo MA, Placidi GPA, Malone KM, Campbell C, Keilp J, Brodsky B, and others. Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression. Arch Gen Psychiatry 2003;60:14–22.
19. Meyer JH, McMain S, Kennedy SH, Korman L, Brown GM, DaSilva JN, and others. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm. Am J Psychiatry 2003;160:90–9
20. Links PS, Gould B, Ratnayake R. The assessment of suicidal youth with antisoial, borderline, or narcissistic personality disorder. Can J Psychiatry 2003:48:301–10.
21. Paris J. Commentary on the American Psychiatric Association guidelines for the treatment of borderline personality disorder: evidence-based psychiatry and the quality of evidence. J Personal Disord 2002;16:130–4.
22. Lambert MT. Suicide risk assessment and management: focus on personality disorders. Curr Opin Psychiatry 2003;16:71–6.
Author(s)
1. Professor Emeritus, Psychiatry and Public Health Sciences, University of Toronto, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, ON, M5T 1R8
e-mail: isaac.sakinofsky@utoronto.ca; Isaac_Sakinofsky@camh.net
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