Several studies have demonstrated that patients with bipolar disorder (BD) are at great risk for suicidal ideation and suicide attempts (SAs).1,2 In clinical samples, about 1/3 to 1/2 of patients with BD report at least one SA during their lives.3,4 Suicidal risk increases in patients with BD who have had a higher number of lifetime manic or depressive episodes or who have a history of rapid cycling.5–9 Other clinical risk factors associated with SAs include early onset of BD, female sex, personal and family history of SAs and suicide, psychiatric hospitalization due to depression, and alcohol and drug abuse.1,2,4,5,8–16 In addition, significant correlations have been reported between SAs and higher rates of cluster B8,12 and cluster C17 personality disorders among patients with BD.
Risks of suicidal ideation and SAs are also increased among patients with BD who have comorbid anxiety disorders (ADs).12,18–29 Several studies have found an association between panic disorder,5,18,24 generalized AD,5,18,21,24,25,28 social AD,18,25 obsessive-compulsive disorder,18,30 and posttraumatic stress disorder (PTSD),18,24,27,30 and SAs among patients with BD. Studies that have examined the relationship between suicidal behavior and comorbid ADs in BD have obtained contradictory results. Some studies have found that there was an independent association between AD comorbidity and rates of SAs when controlling for age, sex, alcohol and substance abuse, affective states, and all other ADs.18–20,25 Other studies have reported that suicidal patients with BD had significantly higher levels of depression and, hopelessness, fewer symptoms of mania, a longer duration of the most recent episode, and a greater current prevalence of comorbid ADs.5,12,13,22,28 Some patients with BD had suicidal ideation and made SAs during a pure31 or mixed32 manic episode. ADs such as social AD and panic disorder have been associated with characteristics of BD such as earlier onset of bipolar illness, greater disability, and poorer course of illness.18,33 These differing findings reflect the diverse definitions of anxiety used in these studies (eg, whether they include lifetime or only recent anxiety symptoms or include all or only some ADs).
Although several forms of anxiety symptoms and disorders have been found to be associated with suicidality in BD, it is not well understood which aspects of anxiety are related to the increased risk of suicidal behaviors in BD. In this study, our primary purpose was to examine the association between lifetime SAs and comorbid ADs in a sample of patients with BD. We also investigated whether certain types of ADs were related to lifetime SAs independent of BD characteristics, including the presence of past affective episodes. We hypothesized that lifetime diagnoses of ADs would influence the occurence of lifetime SAs independent of previous depressive episodes.
Subjects and Assessment
Two hundred fifty-five patients with BD who presented at the psychiatry department of Adnan Menderes University Hospital, Aydin, Turkey, between 2015 and 2017 were screened for inclusion in the study. Inclusion criteria were a diagnosis of BD type I or II and age between 18 and 65 years. Subjects who could not complete the interview because of severe manic symptomatology were not included in the study. The other exclusion criteria were any lifetime psychotic disorders, mental disorders due to another medical condition, and intellectual disabilities. Patients with BD not otherwise specified who developed manic or hypomanic episodes while receiving antidepressant treatment were also not included in the study. Therefore, 200 subjects with BD who were eligible for the study on the basis of the inclusion and exclusion criteria were recruited to the study and gave informed consent after the study was fully explained. The remaining 55 subjects did not participate in the study because they were not eligible (n=48) or declined to sign the informed consent (n=7). This study was approved by the local ethics comittee in the Medical Faculty of Adnan Menderes University.
Lifetime diagnoses of BD and ADs were assessed by a trained clinician (O.K.) using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders (SCID-I).34,35 ADs included panic disorder, agoraphobia, social AD, simple phobia, obsessive-compulsive disorder, PTSD, and generalized AD. The patients were asked if they had ever made a SA after the onset of BD. During the assessment, all patients were being treated with mood stabilizers, antidepressants, and/or antipsychotics.
The demographic characteristics of the participants, including age, sex, years of education, and marital status, were ascertained through a semistructured interview form. We also collected information on several clinical variables such as age at onset of BD, family history of BD and suicide, first episode type, mean number of suicidal acts, comorbid AD diagnoses, episode type at the time of suicidal acts, and duration of periods of untreated illness.
Group comparisons were made using χ2 tests or Fisher exact tests for categorical variables. A Shapiro-Wilk test was used to assess for normal distribution of the data. Because only the mean ages of the patients were normally distributed, the other continous variables were compared using Mann-Whitney U tests. The Student t was used to compare the age differences between the 2 groups. The relationships between number of SAs and predictor variables were assessed by Pearson’s correlation analysis.
As the number of SAs was overdispersed and was consistent with a negative binomial distribution, negative binomial regression was used to predict an outcome of suicidal behavior within the total sample. Through this analysis, we also aimed to decrease the risk of possible experiment-wise errors due to numerous comparisons. The mean number of previous hospitalizations and affective episodes and lifetime diagnoses of social AD and PTSD were determined to be independent variables, because they were found to be significantly higher in the suicidal than in the nonsuicidal group. Morever, sex and family history of suicide, which have previously been reported to be correlated with suicidal behavior in BD,5,12 were added as independent variables.
A second negative binomial regression was performed to delineate the associations of social AD and SAs in the total sample. In this analysis, duration of BD was used as the offset variable to control for differential duration of illness between the groups. All statistical assessments were 2-tailed, and we considered results to be significant at P<0.05. We used SPSS version 18.0 statistical software (SPSS Inc.) to perform our analyses.
A total of 200 patients were included in the study, 64 (32.0%) of whom had at least 1 lifetime SA. Table 1 illustrates the comparisons of suicide attempters and nonattempters with respect to sociodemographic and clinical variables. There were no significant differences in age, sex, marital status, educational level, family history of BD or SA, type of first affective episode, age at onset of BD, and duration of untreated BD between the 2 groups. Although the mean number of lifetime comorbid diagnoses of AD (P=0.06) was found to be higher in suicide attempters than in nonattempters, this difference was not statistically significant. The mean number of previous affective episodes (P=0.03) and prior hospitalizations (P=0.001) and the rates of lifetime diagnoses of social AD (P=0.049) and PTSD (P=0.013) were significantly higher in suicide attempters than in nonattempters. Previous manic (P=0.008), depressive (P=0.032), and hypomanic(P=0.049) episodes were significantly more frequent in the suicidal group compared with the nonsuicidal group. The majority of attempters reported that they were in manic or depressive phases during their suicidal acts.
As indicated in Table 2, there were significant correlations between the mean number of SAs and the mean number of lifetime comorbid AD diagnoses (r=0.263, P=0.036) and duration of untreated illness (r=0.323, P=0.009). Negative binomial regression analysis was used to predict an outcome of suicidal behavior among all participants (Table 3). Duration of BD was used as the offset variable to control for differential duration of illness between the groups being compared. The model was able to predict suicidal behavior [Omnibus χ26=26.098, P<0.001]. Six predictor variables were included in the model, 2 of which successfully predicted suicidal behavior. Participants with a lifetime comorbid diagnosis of social AD were nearly 3 times as likely [incident rate ratio (IRR)=2.885], and the subjects with a lifetime comorbid diagnosis of PTSD were >5 times as likely (IRR, 5.148) to have made a previous SA as those without any lifetime AD diagnoses.
A second negative binomial regression was performed to determine whether comorbid social AD would further predict suicidal behavior among bipolar patients independent of the presence of previous depressive episodes. To test this hypothesis, we selected the 113 of 200 patients with BD in the sample who had no lifetime diagnosis of any AD and the 20 patients of the 32 patients with BD and comorbid social AD who had only that one comorbid AD (Table 4). Two predictors were included in the model, and the model was able to predict suicidal behavior [Omnibus χ22=6.281, P<0.043]. Participants with a lifetime comorbid diagnosis of social AD were 2.67 times (IRR, 2.670) more likely to have made an SA than those without any comorbid AD independent of the presence of previous depressive episodes.
Our primary purpose in this study was to investigate the association of lifetime SAs with comorbid ADs in patients with BD. We particularly wondered to what extent comorbid ADs as well as other sociodemographic and clinical variables were related to past SAs in patients with BD. We sought to explore the association between comorbid anxiety and suicidal thoughts and behaviors in patients with BD by examining the role of certain types of ADs. We further investigated which of these anxiety features predicted suicidal ideation and behavior after adjusting for the confounding effect of previous depressive episodes in multiple regression analyses. In interpreting the results of this study, recall bias should be taken into consideration. In addition, we did not assess for the presence of personality disorders8,12,17 which is known to be a potential risk factor for suicidal behavior.
In this study, we found that 32.0% of our sample had made at least 1 past SA. The mean number of past SAs was significantly correlated with the mean number of lifetime comorbid AD diagnoses and duration of untreated BD. Consistent with the findings in some previous studies,8,9,36 the mean number of previous manic and depressive episodes were significantly higher in suicide attempters than in nonattempters. A previous study found that patients with BD had a higher frequency of depressive first episodes, which is also associated with increased suicide risk.37
In this study, comorbid diagnoses of social AD and PTSD were more common in patients with BD who had made an SA than in nonattempters. However, the small number of comorbid PTSD diagnoses (n=6) in our sample and the wide confidence interval (1.698-15.603) should be acknowledged as limitations of this study. Our regression analysis indicated that lifetime comorbid diagnoses of social AD and PTSD strongly predicted past suicidality among BD patients. Previously, Perroud et al25 had reported that social AD was the only comorbid AD which was associated with lifetime SAs in patients with BD. In that study, although all ADs were more frequently observed among patients with BD who had lifetime SAs than among patients with BDs who had not made an SA, only social AD remained significantly associated with suicidal behavior after logistic regression. In addition, our results indicated that patients with BD with lifetime SAs were more likely to have had previous hospitalizations than those without SAs. Consistent with the report of Perroud et al,25 the number of previous hospitalizations strongly predicted the occurrence of lifetime SAs among patients with BD. Therefore, our findings suggest that past suicidality among patients with BD is associated with comorbid social AD and PTSD, as well the frequency of hospitalizations and affective episodes.
The relationship between social anxiety and suicidality in adolescents and adults has not been well studied to date. A study by Valentiner et al38 found that, after controlling for depression, current social AD symptoms were slightly associated with suicidal ideation but not with suicidal behavior in a sample of high school students. Findings from several studies have indicated that social AD can be considered a risk factor for developing a depressive disorder because it has been shown to precede the onset of mood disorders.39,40 In our study, social AD was not found to act as a trigger for increased frequency of depressive episodes in patients with BD. When we performed a regression analysis to control the influence of previous depressive episodes on the SAs of the patients with social AD, we found that the presence of social AD without other AD comorbidity continued to be associated with lifetime SAs independent of previous depressive episodes. Therefore, we suggest that social AD is itself associated with a greater risk of occurrence of SAs in patients with BD independent of depression. Morever, our results demonstrated that a lifetime diagnosis of PTSD and more frequent previous hospitalizations made a significant contribution to the occurrence of lifetime SAs in individuals with BD. The only surprising finding in our study was that previous manic episodes were more frequent in the patients with BD who attempted suicide than in those who were nonattempters. However, this difference did not seem to be predictive of past suicidal acts; in addition, the lack of association between social AD and the frequency of previous affective episodes might suggest that the influence of social AD on past SAs is independent of these variables.
The main findings of this study were that comorbid diagnoses of social AD and PTSD were more common in suicidal patients with BD than in nonsuicidal patients with BD. Lifetime comorbid diagnoses of social AD and PTSD strongly predicted the occurrence of past suicidality. Patients with BD with lifetime SAs were also more likely to have had previous hospitalizations than those without SAs, and the number of previous hospitalizations strongly predicted the occurrence of lifetime SAs among patients with BD. The presence of lifetime social AD without other AD comorbidity was significantly associated with lifetime SAs independent of previous depressive episodes. Therefore, we suggest that social AD itself is associated with a greater risk of occurrence of SAs in patients with BD independent of depression. The relationship of comorbid social AD and cluster B personality disorders with respect to risk for suicidal behavior in patients with BD should be evaluated in future studies.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
bipolar disorder; anxiety disorders; suicide attempts; social anxiety disorder; posttraumatic stress disorder