© 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.
Bipolar Disorders 2014
BIPOLAR DISORDERS
Commentary
Identification of suicide risk in bipolar disorder Lopez-Castroman J, Courtet P, Baca-Garcia E, Oquendo MA. Identification of suicide risk in bipolar disorder. Bipolar Disord 2014: 00: 000–000. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Jorge Lopez-Castromana,b, Philippe Courteta,c, Enrique Baca-Garciab,d and Maria A Oquendod a
Department of Emergency Psychiatry, CHRU Montpellier, Montpellier, France, bIIS-Fundacion Jimenez Diaz, Department of Psychiatry, CIBERSAM, Madrid, Spain, cUniversity of Montpellier 1, Montpellier, France, dDepartment of Psychiatry, New York State Psychiatric Institute and Columbia University, New York, NY, USA Key words: bipolar disorder – correlates – suicide – suicide attempt
Among all psychiatric conditions, bipolar disorder carries the greatest risk for suicide attempt or death (1). Schaffer et al. (2) recently conducted a meta-analysis to identify demographic and clinical correlates of suicidal behavior in bipolar disorder. However, the heterogeneity of existing studies prevented the analysis of several relevant risk factors for suicidal behavior, such as previous history of suicide attempts, life adversities, or mixed polarity of the affective episodes. Nonetheless, their findings provide a consolidated clinical profile of high-risk individuals with bipolar disorder. According to this profile, suicide attempts are particularly associated with two conditions: a current or recent depressive episode and a comorbid cluster B/borderline personality disorder [odds ratio (OR) = 5.99 and OR = 2.51, respectively]. Their analyses also confirm the predictive importance of the first episode of bipolar disorder in the determination of suicidal risk – when the disease starts early in life or with a depressive episode, the risk of future suicide attempts is increased. On the other hand, suicide deaths in subjects with bipolar disorder are almost threefold for those with a firstdegree family history of suicide and doubled in males (OR = 2.91 and OR = 1.83, respectively). Of note, the former data point can be obtained by asking a single question during clinical assessment and is also associated with risk of suicide attempts. Another relevant finding of their study concerns
the lack of effect of bipolar disorder subtype on suicidal risk, an issue that has been the subject of debate for some time (3). Overall, the literature suggests that bipolar disorder might be associated with specific vulnerabilities for suicidal behavior not present in other mental disorders. Suicidal behavior and bipolar disorder appear to share vulnerability factors, endophenotypes, and susceptibility genes, which may explain the high suicide risk associated with this disorder. Some interesting examples follow. First, neuroimaging studies have shown that neural network abnormalities related to suicide risk, such as reduced orbitofrontal and ventral prefrontal cortex activity (4), are also found among patients with bipolar disorder (5). Second, decision-making impairment, a cognitive trait associated with suicidal behavior, has been reported in patients with bipolar disorder (6), especially if suicidal (7). Similarly, reduced gray matter volumes in areas such as the dorsolateral prefrontal cortex or orbitofrontal cortex have been suggested as biological correlates of impaired decision-making among depressed patients with bipolar disorder and a history of suicide attempts (8). Third, lithium may have anti-suicidal properties but it is still unclear if a similar effect can be achieved with other mood stabilizers, such as valproate (9). Fourth, some personality traits appear to characterize suicide risk in patients with bipolar disorder. For instance, hostility and
1
Lopez-Castroman et al. irritability traits have been associated with suicidal risk in these patients (10), while impulsivity could be a reliable suicide risk marker in unipolar patients, but not in patients with bipolar disorder (11). Fifth, regarding genetic susceptibility, although the inherited risk for suicide in bipolar disorder is unlikely to be caused by single genetic variations, there is evidence for the implication of multiple loci in the genetic transmission of risk (12). A promising line of research combining different methods has recently shown that the elevated expression of certain ribonucleic acid biomarkers might predict future suicide attempts among subjects with bipolar disorder (13). Lastly, compared to unipolar depression, the increased risk of suicidal behaviors in bipolar disorder might be driven by the long duration of high-risk illness phases (3). There is still a long way to go before we can accurately identify high-risk individuals with bipolar disorder. We still rely on clinical assessments but known risk factors are not specific enough (14). The study by Schaffer et al. provides an excellent update on the state of the cross-sectional literature on demographic and clinical correlates of suicidal behavior in patients with bipolar disorder. Now, the challenge is to integrate their findings with biologically based and neurocognitive studies into a comprehensive model in order to increase the sensitivity and specificity of suicidal risk assessments for patients with bipolar disorder and to test their utility prospectively. Disclosures The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
References 1. Yerevanian BI, Choi YM. Impact of psychotropic drugs on suicide and suicidal behaviors. Bipolar Disord 2013; 15: 594–621. 2. Schaffer A, Isomets€ a ET, Tondo L et al. International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder. Bipolar Disord 2014; in press.
2
3. Holma KM, Haukka J, Suominen K et al. Differences in incidence of suicide attempts between bipolar I and II disorders and major depressive disorder. Bipolar Disord 2014; 16: 652–661. 4. Raust A, Slama F, Mathieu F et al. Prefrontal cortex dysfunction in patients with suicidal behavior. Psychol Med 2007; 37: 411–419. 5. Langan C, McDonald C. Neurobiological trait abnormalities in bipolar disorder. Mol Psychiatry 2009; 9: 833–846. 6. Adida M, Jollant F, Clark L et al. Trait-related decisionmaking impairment in the three phases of bipolar disorder. Biol Psychiatry 2011; 70: 357–365. 7. Martino DJ, Strejilevich SA, Torralva T, Manes F. Decision making in euthymic bipolar I and bipolar II disorders. Psychol Med 2011; 41: 1319–1327. 8. Benedetti F, Radaelli D, Poletti S et al. Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression. J Affect Disord 2011; 135: 139–147. 9. Oquendo MA, Galfalvy HC, Currier D et al. Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. Am J Psychiatry 2011; 168: 1050–1056. 10. Parmentier C, Etain B, Yon L, et al. Clinical and dimensional characteristics of euthymic bipolar patients with or without suicidal behavior. Eur Psychiatry 2012; 27: 570– 576. 11. Perroud N, Baud P, Mouthon D, Courtet P, Malafosse A. Impulsivity, aggression and suicidal behavior in unipolar and bipolar disorders. J Affect Disord 2011; 134: 112–118. 12. Mathews DC, Richards EM, Niciu MJ, Ionescu DF, Rasimas JJ, Zarate CAJr. Neurobiological aspects of suicide and suicide attempts in bipolar disorder. Transl Neurosci 2013; 4. 13. Le-Niculescu H, Levey DF, Ayalew M et al. Discovery and validation of blood biomarkers for suicidality. Mol Psychiatry 2013; 18: 1249–1264. 14. Saunders KE, Hawton K. Clinical assessment and crisis intervention for the suicidal bipolar disorder patient. Bipolar Disord 2013; 15: 575–583. Corresponding author: Maria A. Oquendo, M.D. Department of Psychiatry Columbia University New York State Psychiatric Unit #88 1051 Riverside Drive, Box #42 New York, NY 10032 USA Fax: 212-543-6017 E-mail: [email protected] doi: 10.1111/bdi.12264
Bipolar Disorders 2014
BIPOLAR DISORDERS
Commentary
Identification of suicide risk in bipolar disorder Lopez-Castroman J, Courtet P, Baca-Garcia E, Oquendo MA. Identification of suicide risk in bipolar disorder. Bipolar Disord 2014: 00: 000–000. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Jorge Lopez-Castromana,b, Philippe Courteta,c, Enrique Baca-Garciab,d and Maria A Oquendod a
Department of Emergency Psychiatry, CHRU Montpellier, Montpellier, France, bIIS-Fundacion Jimenez Diaz, Department of Psychiatry, CIBERSAM, Madrid, Spain, cUniversity of Montpellier 1, Montpellier, France, dDepartment of Psychiatry, New York State Psychiatric Institute and Columbia University, New York, NY, USA Key words: bipolar disorder – correlates – suicide – suicide attempt
Among all psychiatric conditions, bipolar disorder carries the greatest risk for suicide attempt or death (1). Schaffer et al. (2) recently conducted a meta-analysis to identify demographic and clinical correlates of suicidal behavior in bipolar disorder. However, the heterogeneity of existing studies prevented the analysis of several relevant risk factors for suicidal behavior, such as previous history of suicide attempts, life adversities, or mixed polarity of the affective episodes. Nonetheless, their findings provide a consolidated clinical profile of high-risk individuals with bipolar disorder. According to this profile, suicide attempts are particularly associated with two conditions: a current or recent depressive episode and a comorbid cluster B/borderline personality disorder [odds ratio (OR) = 5.99 and OR = 2.51, respectively]. Their analyses also confirm the predictive importance of the first episode of bipolar disorder in the determination of suicidal risk – when the disease starts early in life or with a depressive episode, the risk of future suicide attempts is increased. On the other hand, suicide deaths in subjects with bipolar disorder are almost threefold for those with a firstdegree family history of suicide and doubled in males (OR = 2.91 and OR = 1.83, respectively). Of note, the former data point can be obtained by asking a single question during clinical assessment and is also associated with risk of suicide attempts. Another relevant finding of their study concerns
the lack of effect of bipolar disorder subtype on suicidal risk, an issue that has been the subject of debate for some time (3). Overall, the literature suggests that bipolar disorder might be associated with specific vulnerabilities for suicidal behavior not present in other mental disorders. Suicidal behavior and bipolar disorder appear to share vulnerability factors, endophenotypes, and susceptibility genes, which may explain the high suicide risk associated with this disorder. Some interesting examples follow. First, neuroimaging studies have shown that neural network abnormalities related to suicide risk, such as reduced orbitofrontal and ventral prefrontal cortex activity (4), are also found among patients with bipolar disorder (5). Second, decision-making impairment, a cognitive trait associated with suicidal behavior, has been reported in patients with bipolar disorder (6), especially if suicidal (7). Similarly, reduced gray matter volumes in areas such as the dorsolateral prefrontal cortex or orbitofrontal cortex have been suggested as biological correlates of impaired decision-making among depressed patients with bipolar disorder and a history of suicide attempts (8). Third, lithium may have anti-suicidal properties but it is still unclear if a similar effect can be achieved with other mood stabilizers, such as valproate (9). Fourth, some personality traits appear to characterize suicide risk in patients with bipolar disorder. For instance, hostility and
1
Lopez-Castroman et al. irritability traits have been associated with suicidal risk in these patients (10), while impulsivity could be a reliable suicide risk marker in unipolar patients, but not in patients with bipolar disorder (11). Fifth, regarding genetic susceptibility, although the inherited risk for suicide in bipolar disorder is unlikely to be caused by single genetic variations, there is evidence for the implication of multiple loci in the genetic transmission of risk (12). A promising line of research combining different methods has recently shown that the elevated expression of certain ribonucleic acid biomarkers might predict future suicide attempts among subjects with bipolar disorder (13). Lastly, compared to unipolar depression, the increased risk of suicidal behaviors in bipolar disorder might be driven by the long duration of high-risk illness phases (3). There is still a long way to go before we can accurately identify high-risk individuals with bipolar disorder. We still rely on clinical assessments but known risk factors are not specific enough (14). The study by Schaffer et al. provides an excellent update on the state of the cross-sectional literature on demographic and clinical correlates of suicidal behavior in patients with bipolar disorder. Now, the challenge is to integrate their findings with biologically based and neurocognitive studies into a comprehensive model in order to increase the sensitivity and specificity of suicidal risk assessments for patients with bipolar disorder and to test their utility prospectively. Disclosures The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
References 1. Yerevanian BI, Choi YM. Impact of psychotropic drugs on suicide and suicidal behaviors. Bipolar Disord 2013; 15: 594–621. 2. Schaffer A, Isomets€ a ET, Tondo L et al. International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder. Bipolar Disord 2014; in press.
2
3. Holma KM, Haukka J, Suominen K et al. Differences in incidence of suicide attempts between bipolar I and II disorders and major depressive disorder. Bipolar Disord 2014; 16: 652–661. 4. Raust A, Slama F, Mathieu F et al. Prefrontal cortex dysfunction in patients with suicidal behavior. Psychol Med 2007; 37: 411–419. 5. Langan C, McDonald C. Neurobiological trait abnormalities in bipolar disorder. Mol Psychiatry 2009; 9: 833–846. 6. Adida M, Jollant F, Clark L et al. Trait-related decisionmaking impairment in the three phases of bipolar disorder. Biol Psychiatry 2011; 70: 357–365. 7. Martino DJ, Strejilevich SA, Torralva T, Manes F. Decision making in euthymic bipolar I and bipolar II disorders. Psychol Med 2011; 41: 1319–1327. 8. Benedetti F, Radaelli D, Poletti S et al. Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression. J Affect Disord 2011; 135: 139–147. 9. Oquendo MA, Galfalvy HC, Currier D et al. Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. Am J Psychiatry 2011; 168: 1050–1056. 10. Parmentier C, Etain B, Yon L, et al. Clinical and dimensional characteristics of euthymic bipolar patients with or without suicidal behavior. Eur Psychiatry 2012; 27: 570– 576. 11. Perroud N, Baud P, Mouthon D, Courtet P, Malafosse A. Impulsivity, aggression and suicidal behavior in unipolar and bipolar disorders. J Affect Disord 2011; 134: 112–118. 12. Mathews DC, Richards EM, Niciu MJ, Ionescu DF, Rasimas JJ, Zarate CAJr. Neurobiological aspects of suicide and suicide attempts in bipolar disorder. Transl Neurosci 2013; 4. 13. Le-Niculescu H, Levey DF, Ayalew M et al. Discovery and validation of blood biomarkers for suicidality. Mol Psychiatry 2013; 18: 1249–1264. 14. Saunders KE, Hawton K. Clinical assessment and crisis intervention for the suicidal bipolar disorder patient. Bipolar Disord 2013; 15: 575–583. Corresponding author: Maria A. Oquendo, M.D. Department of Psychiatry Columbia University New York State Psychiatric Unit #88 1051 Riverside Drive, Box #42 New York, NY 10032 USA Fax: 212-543-6017 E-mail: [email protected] doi: 10.1111/bdi.12264
