Introduction

Bipolar disorder is a major public health concern worldwide, and is associated with significant morbidity and mortality Reference Kupfer(1). In addition to an increased rate of death by suicide, community and clinical studies indicate that bipolar patients usually present a broad range of comorbid general medical conditions, which contribute to overall mortality rates Reference Angst, Stassen, Clayton and Angst(2,Reference Roshanaei-Moghaddam and Katon3).

Of significant interest is the co-occurrence of metabolic disturbances in bipolar disorder, particularly obesity. In addition to the burden related to the expanding obesity epidemic in both developed and developing countries such as Brazil, in which prevalence rates have reached up to 11% of the population (4), bipolar disorder and comorbid obesity are associated with increased medical morbidity and worse psychiatric outcome Reference Wildes, Marcus and Fagiolini(5). Data from clinical samples have shown that the prevalence of obesity in bipolar disorder patients is exceedingly high, ranging from 20 to 35%, when compared with controls (Reference Elmslie, Silverstone, Mann, Williams and Romans6–Reference Fagiolini, Kupfer, Houck, Novick and Frank8), even in those not exposed to the weight gaining effects of pharmacological treatments Reference Taylor, Macdonald, McKinnon, Joffe and MacQueen(9,Reference Maina, Salvi, Vitalucci, D’Ambrosio and Bogetto10). Furthermore, obese patients usually have more markers of illness severity, such as more previous affective episodes Reference Fagiolini, Frank and Houck(11) and suicide attempts (Reference Fagiolini, Kupfer, Rucci, Scott, Novick and Frank12–Reference Wang, Sachs and Zarate14).

Recent studies have addressed the relationship between obesity and psychiatric morbidity Reference McElroy, Kotwal, Malhotra, Nelson, Keck and Nemeroff(15). Data from community surveys from the United States Reference Carpenter, Hasin, Allison and Faith(16) and Canada Reference Mather, Cox, Enns and Sareen(17) have indicated that obesity has been associated with suicidal behaviour, particularly suicidal ideation and previous attempts. This is of particular concern because both obesity and suicidal behaviour are common features of bipolar disorder Reference McIntyre, Muzina and Kemp(18). A recent meta-analysis of 36 suicide studies in this patient population identified several risk factors for suicide, including early onset of mood episodes, longer duration of depressive symptoms, rapid cycling, family history of suicide, previous suicide attempts and comorbid psychiatric conditions such as substance use disorders Reference Hawton, Sutton, Haw, Sinclair and Harriss(19).

Only a couple of studies have investigated the association of obesity and suicidal behaviour in this group of patients. Fagiolini et al. Reference Fagiolini, Kupfer, Rucci, Scott, Novick and Frank(12) found a positive association between a higher body mass index (BMI) and previous suicide attempts at baseline, in a sample of 175 patients with bipolar I disorder participating in a clinical trial. Similarly, a second cross-sectional study of 171 patients by the same research group Reference Fagiolini, Frank, Scott, Turkin and Kupfer(13) reported an association between both a diagnosis of the metabolic syndrome and the presence of abdominal obesity, and a lifetime history of suicidal behaviour.

There remains a paucity of data regarding this association, with no studies from outside the United States and a relatively low number of patients in previous reports. This study, therefore, aimed to further examine an independent relationship of obesity and suicide attempts in a larger sample of patients with bipolar disorder.

Materials and methods

Results

The sample consisted of 255 bipolar patients. A history of suicide attempts was present in 133 subjects (52.2%) and 80 patients (31.4%) were classified as obese. Table 1 shows sociodemographic and clinical variables of the sample. The majority of patients (87.8%) were taking mood stabilisers (lithium, valproate or carbamazepine) alone or in combination, 20.4% were on atypical antipsychotics and 23.5% were receiving antidepressants.

Table 1 Clinical and demographic variables in patients with and without suicide attempts

Obese patients were twice as likely to have a history of suicide attempts (OR = 2.00, 95% CI: 1.16–3.44, p = 0.02). Furthermore, obesity was not associated with depressive symptoms (p = 0.77), rapid cycling (p = 0.068) or anxiety (p = 0.67), alcohol (p = 0.87) and drug use disorders (p = 0.24). Data regarding treatment regimens are presented in Table 2.

Table 2 Treatment regimens according to patient groups

Obesity remained associated with suicide attempts in the regression model (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03). Also associated with suicide attempts in the final model were lifetime anxiety (OR = 2.15, 95% CI: 1.22–3.78, p = 0.008) and substance use disorders (OR = 2.36, 95% CI: 1.29–4.30, p = 0.005), rapid cycling (OR = 2.09, 95% CI: 1.09–4.00, p = 0.027) and current depressive symptoms (OR = 1.06, 95% CI: 1.02–1.10, p = 0.005). Age (OR = 0.99, 95% CI: 0.97–1.01, p = 0.403) and sex (OR = 1.47, 95% CI: 0.83–2.60, p = 0.191) were dropped from the final model.

Discussion

The main finding of this study is that obesity was associated with a history of suicide attempts in a sample of out-patients with bipolar disorder, even after controlling for well-established risk factors such as lifetime comorbid anxiety and alcohol use disorders and depressive symptoms.

Our finding adds to the notion that obesity is a correlate of severity in patients with bipolar disorder, and replicates earlier findings from Fagiolini et al. Reference Fagiolini, Kupfer, Rucci, Scott, Novick and Frank(12,Reference Fagiolini, Frank, Scott, Turkin and Kupfer13). In recent years, there has been an increasing interest in the relationship of obesity and psychiatric disorders Reference Berkowitz and Fabricatore(25), particularly bipolar disorder Reference Wildes, Marcus and Fagiolini(5), because weight gain and obesity frequently complicate treatment of mood disorders Reference McElroy, Kotwal, Malhotra, Nelson, Keck and Nemeroff(15). Furthermore, obese patients with bipolar disorder usually have more markers of adverse outcome, such as greater number of comorbid general medical conditions, increased number of previous mood episodes and more depressive features (Reference McElroy, Frye and Suppes7,Reference Fagiolini, Kupfer, Houck, Novick and Frank8,Reference Fagiolini, Frank, Scott, Turkin and Kupfer13).

We also found a significant association between suicide attempts and comorbid anxiety and alcohol use disorders and depressive symptoms. This is in line with previous findings from our group Reference Cardoso, Kauer Sant’Anna, Dias, Andreazza, Ceresér and Kapczinski(26,Reference Rosa, Andreazza and Kunz27). Bipolar patients with a history of suicide attempts have been shown to have more markers of severity such as greater suicidal ideation, increased number of hospitalisations, aggressive traits, earlier age at onset Reference Grunebaum, Ramsay and Galfalvy(28), a family history of suicide Reference Sánchez-Gistau, Colom, Mané, Romero, Sugranyes and Vieta(29) and of psychiatric and mood disorders Reference Rosa, Franco and Martínez-Aran(30), as well as a higher frequency of comorbid anxiety, substance use and cluster B personality disorders (Reference Sánchez-Gistau, Colom, Mané, Romero, Sugranyes and Vieta29–Reference Neves, Malloy-Diniz and Corrêa32).

One possible link between obesity and suicide in bipolar disorder may be related to depression. Major depression and residual depressive symptoms are the most common phases of bipolar disorder and both are associated with substantial work, social and family functional impairment Reference Post(33). Depressive episodes are related to changes in appetite, eating behaviour and physical activity that contribute to obesity Reference Wildes, Marcus and Fagiolini(5). Bipolar depression differs from unipolar depression in key symptom patterns, with atypical features, particularly hypersomnia and hyperphagia being prominent Reference Berk, Malhi and Mitchell(34). In addition to the fact that bipolar disorder with predominant depressive polarity is strongly related to suicidal behaviour Reference Rosa, Andreazza and Kunz(27,Reference Colom, Vieta, Daban, Pacchiarotti and Sánchez-Moreno35), a recent report has shown that depression with atypical features is also associated with suicide in this population Reference Sánchez-Gistau, Colom, Mané, Romero, Sugranyes and Vieta(29). We also found a positive association of both depressive symptoms and obesity with suicide attempts.

Recent data have stressed common features in the underlying pathophysiology of obesity and bipolar disorder which may also be another possible explanation for our findings. Leptin, a key hormone in regulation of adiposity has been shown to be positively associated with risk for depression in a prospective study Reference Pasco, Jacka and Williams(36). Disturbances in metabolic pathways such as insulin-mediated glucose homeostasis, overactivation of the hypothalamic–pituitary–adrenal axis, dysregulated immune and inflammatory processes and adipocytokines profiles are present in both conditions Reference McIntyre, Soczynska and Konarski(37). Such deleterious alterations in key adaptive mechanisms are a component of allostatic load Reference McEwen(38) and may explain some of the complex interactions among bipolar disorder, common general medical conditions and resilience to mood episodes and life events Reference Kapczinski, Vieta and Andreazza(39). This framework provides another standpoint from which obesity may be seen as a correlate of allostatic load in bipolar disorder and its relationship with suicide attempts a marker of illness severity.

This report described a cross-sectional study in a tertiary treatment setting. Most of our sample consists of difficult-to-treat patients referred to the Bipolar Disorder Program, which may limit the ability to generalise our results to the whole spectrum of bipolar disorder. The retrospective assessment of some variables may be influenced by recall bias; because of the complex nature of obesity and suicidal behaviour, prospective studies are needed to further clarify the causal nature of this association.

In addition to well-established risk factors such as previous suicide attempts, depressive symptoms and comorbid psychiatric conditions, clinicians must be aware that obesity may be a severity feature relevant not only to pharmacological treatment decisions but also to the comprehensive management of bipolar disorder. It is plausible to speculate that therapeutic interventions targeted to obesity may be of potential benefit in the course of bipolar disorder.