The Impact of BMI on Clinical Features of Bipolar Disorder

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CASE VIGNETTE

“Mr Lee” is a 32-year-old male with a history of bipolar I disorder, with depression during his most recent episode. The onset of his mood disorder was at age 21 years. He failed previous trials of valproic acid and aripiprazole. He has a history of 2 suicide attempts by overdose on medications. He was also previously treated with a course of electroconvulsive therapy (ECT).

He has been taking lithium 900 mg daily for the past 5 years. During this time, he has not had any episodes of mania, but he does have chronic mild depressive symptoms. He has a history of comorbid obesity and type 2 diabetes, but he does not have hypertension or hyperlipidemia. His current body mass index (BMI) is 38.

At an outpatient visit, Mr Lee expresses a desire to try to exercise by walking while his son plays at a local park. He asks about the potential mental health benefits of exercise. As his psychiatrist, how would you respond?

Bipolar disorder is associated with a 2- to 3-fold increased risk of premature mortality, with an average reduced lifespan of 9 to 17 years.¹ Obesity rates in the United States are increasing,² and individuals with mood disorders, including bipolar disorder, are at increased risk.^3,4 Suicide mortality in the United States is also increasing,⁵ although evidence for an association between obesity and suicidal behavior is inconsistent.

There is also evidence that increased low-grade inflammation, associated with higher BMI, may be associated with a more severe course of illness in patients with bipolar disorder.^6,7

The Current Study

Kadriu and colleagues⁸ aimed to assess whether higher BMI affected disease course and severity, symptom severity, and disease burden (medical and psychiatric comorbidity) in patients with bipolar disorder from the 7-year, longitudinal Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study.⁹

Participants met DSM-IV criteria for bipolar disorder, cyclothymia, or schizoaffective disorder, bipolar type. Psychiatric comorbidities, including anxiety disorders, substance use disorders, eating disorders, and attention-deficit/hyperactivity disorder were also permitted.

Participants were treated in a naturalistic setting. Study investigators included 2790 outpatients with data on height and weight. Data were also available on current mood, medical and psychiatric comorbidities, medication use, adverse effects, substance use, stressors, care utilization, history of ECT, history of suicide attempt, bipolarity index, the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).

Participants were grouped into 7 categories by BMI: underweight (<18.5), thin (18.5-20), normal (20 to 25), overweight (25 to 30), class I obesity (30 to 35), class II obesity (35 to 40), and class III obesity (>40). The investigators used a network-based approach (Watts-Strogatz) to assess the influence of BMI on comorbidities. Relationships between BMI and psychosocial variables were assessed with logistic regression. The association between BMI and mood symptoms was assessed with linear regression.

The mean participant age was 40 years, and 54% of participants were female. The average BMI was 28.4 ± 6.4 (median 27.2). Sex was significantly different across BMI categories (females were more likely to be underweight, and males were more likely to be obese.) Overweight and obese patients had a significantly higher bipolarity index. History of previous ECT treatment was also significantly different across BMI categories (lowest prevalence in the BMI <20 groups).

There was a significant relationship between higher BMI and history of suicide attempt, with the highest prevalence in individuals with class III obesity. There was evidence of a bimodal distribution for BMI and the number of hospitalizations during the study, although the findings did not reach statistical significance.

There was no significant difference in depressive episodes across BMI categories. However, manic episodes, bipolar II disorder diagnosis, panic disorder, social phobia, and posttraumatic stress disorder all differed significantly by BMI groups. Graph theory demonstrated a robust linear increase in comorbidities with increasing BMI. Trajectory clustering analysis indicated that higher BMIs were associated with worsening trajectory of core depressive symptoms.

Study Conclusions

In the STEP-BD study, the investigators found that BMI was associated with greater symptom severity, a greater number of psychiatric and medical comorbidities, a history of ECT, and a worsening trajectory of core depressive symptoms. The investigators noted factors such as obesity, hypothalamic pituitary adrenal (HPA) axis activation, and inflammation as potential mechanisms underlying these associations.¹⁰

Study strengths included the large sample size, real-world data, long-term continuity of care, and rigorous statistical analyses. Study limitations included the use cross-sectional data (which delimits inferences about causality), the exploratory nature of some of the analyses, the inability to account for fluctuations in weight over the course of the study, that all study sites were in the United States, that BMI cannot delineate subcutaneous versus visceral adiposity, and the absence of data on waist circumference or waist-to-hip ratio.

The Bottom Line

The study findings suggest that higher BMI adversely affects disease course and severity in individuals with bipolar disorder. Therefore, this measure is germane to the clinical care of this patient population.

Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times®. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. Kessing LV, Vradi E, Andersen PK. Life expectancy in bipolar disorder. Bipolar Disord. 2015;17(5):543-548.

2. Fryar CD, Kruszon-Moran D, Gu Q, Ogden CL. Mean body weight, height, waist circumference, and body mass index among adults: United States, 1999-2000 through 2015-2016. Natl Health Stat Report. 2018;(122):1-16.

3. Goldstein BI, Liu SM, Zivkovic N, et al. The burden of obesity among adults with bipolar disorder in the United States. Bipolar Disord. 2011;13(4):387-395.

4. Simon GE, Von Korff M, Saunders K, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63(7):824-830.

5. Hedegaard H, Curtin SC, Warner M. Suicide mortality in the United States, 1999-2017. NCHS Data Brief. 2018;(330):1-8.

6. Bond DJ, Andreazza AC, Hughes J, et al. A longitudinal study of the relationships between mood symptoms, body mass index, and serum adipokines in bipolar disorder. J Clin Psychiatry. 2017;78(4):441-448.

7. Bond DJ, Andreazza AC, Hughes J, et al. Association of peripheral inflammation with body mass index and depressive relapse in bipolar disorder. Psychoneuroendocrinology. 2016;65:76-83.

8. Kadriu B, Deng ZD, Kraus C, et al. The impact of body mass index on the clinical features of bipolar disorder: a STEP-BD study. Bipolar Disord. Published online August 3, 2023.

9. Sachs GS, Thase ME, Otto MW, et al. Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003;53(11):1028-1042.

10. Gomes FA, Kauer-Sant'Anna M, Magalhães PV, et al. Obesity is associated with previous suicide attempts in bipolar disorder. Acta Neuropsychiatr. 2010;22(2):63-67.