Elsevier

Journal of Affective Disorders

Volume 171, 15 January 2015, Pages 33-38
Journal of Affective Disorders

Research report
Weight cycling in bipolar disorder

https://doi.org/10.1016/j.jad.2014.09.006Get rights and content

Abstract

Background

An association between excess weight and/or weight fluctuations and cardiovascular morbidity and mortality is amply documented. Individuals with bipolar disorder (BD) are differentially affected by overweight/obesity, chaotic eating patterns (e.g., binge eating), as well as cardiovascular morbidity and mortality. Weight cycling (WCYC) is defined as a pattern of repetitive weight loss and gain.

Methods

We sought to determine the relationship between course of illness and BD and WCYC retrospectively as well whether these co-occurring phenotypes identify a biologically distinct subpopulation on the basis of having a unique inflammatory biomarker/biosignature profile. Sociodemographic, clinical, and inflammatory markers were gathered from a well-characterized cohort of actual euthymic adults with BD (n=101) and a healthy control group (n=48).

Results

Individuals with BD with a history of WCYC were provided evidence of a greater frequency of prior episodes (i.e., both manic and depressed), as well as of significantly higher levels of circulating IL-6 concentrations when compared to non-WCYC individuals with BD. The association persisted after adjusting for relevant covariates (e.g., BMI, age, number of prior episodes).

Limitations

Include the small control group, differing medication status and that all data relies on personal information. Nevertheless we tried to verify all data as far as clinical disclosure was available.

Conclusion

The results of this study indicate that adults with BD excessive in weight are not only more susceptible to a relapse-prone course of illness, but also are more likely to present with WCYC. The finding of elevated pro-inflammatory cytokines in this subpopulation may identify a separate subpopulation with greater susceptibility to cardiovascular disease. The overarching aim of personalized treatment and preventive strategies in BD begins with appropriate, empirically supported patient stratification. Our results provide preliminary support for stratifying BD cardiovascular risk on the basis of anthropometrics and WCYC.

Introduction

The association between excess weight and adverse health outcomes is well established. In addition weight cycling (WCYC), which is a different phenomenon, is independently associated with adverse health outcomes as increased cardiovascular morbidity/mortality and psychological symptoms (Blair et al., 1993, Diaz et al., 2005, Hamm et al., 1989, Lissner et al., 1991, Peters et al., 1995). Weight loss may be an ideal approach to counteract the negative consequences of obesity. However, even when weight loss is achieved, losses are rarely maintained (Wing and Hill, 2001). After one cycle of gaining and losing weight the second regain is faster than the first increase of weight (Brownell et al., 1986, Field et al., 1999).

Repeated periods of weight loss and regain have been termed WCYC. In the general population between 29% and 78% of women and about 18% of men show some degree of WCYC (Field et al., 1999, Lahti-Koski et al., 2005).

The pathways from WCYC to an increased cardiovascular mortality are not well understood. However, several cardiovascular risk factors associated with WCYC have already been identified as e.g. total body and visceral body fat accumulation, changes in the fatty acid composition in the accumulated fat, fluctuations in renal function, plasma glucose, insulin, blood lipids, blood pressure and heart rate (Montani et al., 2006). It has been suggested that WCYC might be associated with systemic low grade inflammation—a factor that also significantly contributes to the development of cardiovascular morbidity (Strohacker and McFarlin, 2010). A general association between WCYC and psychological symptoms has been described in the literature—mainly in obese persons—as WCYC was found to be linked with the feelings of loss of control, personal failure, and decreased self-esteem. A recent study gives evidence for WCYC as a key component of interpersonal oversensitivity (Kensinger et al., 1998, QUOVADIS Study Group, 2007). There is an interest in investigations which aim to verify whether WCYC causes depression or results from it (Luppino et al., 2010, QUOVADIS Study Group, 2004). An association between WCYC and depression in obesity in mentally healthy probands has been reported before (Kensinger et al., 1998, Muls et al., 1995, Walfish, 2004, Womble et al., 2001) but has been denied in other settings (Bartlett et al., 1996, Foster et al., 1996, Simkin-Silverman et al., 1998). One reason for the controversial results in previous studies is the failure of a standardized definition of WCYC. Furthermore, intake of mood stabilizers and antipsychotics and also weight loss in the case of incompliance or during depressive and manic episodes might contribute to weight instability.

Bipolar affective disorder (BD) is a severe and lifelong psychiatric disorder defined by recurrent pathological disturbance in mood and the presence of mania. Individuals suffering from BD have an abnormal anthropometric profile. Overweight and the appearance of metabolic syndrome are observed to be over-represented in this group. Furthermore, there is evidence that the excess weight in BD is hazardous to both mental and physical health outcomes (McIntyre et al., 2010). Overweight/obese individuals with BD have a higher risk of medical co-morbidities, increased mortality as well as an increased frequency of manic and depressive episodes, shorter periods of euthymia and higher rates of suicide attempts compared to normal-weight individuals with BD. This empirical finding is not sufficiently explained by behavioral and/or iatrogenic factors (Bond et al., 2011, Fagiolini et al., 2005, Maina et al., 2008, Wang et al., 2006, Yim et al., 2012). The connection between increased medical co-morbidities and BD is probably mediated by a chronic low-grade inflammatory state. This includes increased stress-activation and alterations in the hypothalamic–pituitary–adrenal axis activation as well as hyperglycemia and hyperinsulinemia leading to an accumulation of chronic allostatic load which may lead to damage in the brain and other body systems (Soczynska et al., 2011).

Mechanistic pathways subserving the relationship between metabolic morbidity and an adverse BD presentation are not sufficiently parsed. Existing studies indicate that chronic stress-sensitive medical conditions, such as cardiovascular disease, obesity and diabetes are found to be the most significant causes of mortality amongst patients with BD; in women, the mortality caused by medical co-morbidity is even higher (Kupfer, 2005, McIntyre et al., 2007).

There is lack of evidence whether simple weight reduction has positive influence on the course of BD and whether regaining weight is associated with a worsening of disease. We therefore evaluated the history of WCYC in a cohort of euthymic individuals with BD. We used the WCYC classification of the Nurses Health Study which defined WCYC as losing at least 4.5 kg for at least three times during the last 4 years (Field et al., 1999).

To date, WCYC in individuals with BD has not been reported in the literature. Nevertheless, we know from previous studies that individuals with BD are differentially affected by binge eating disorder which is directionally consistent with obesity and abnormal weight trajectory (McElroy et al., 2013).

The overarching aim of this investigation was to extend the existing knowledge by reporting on the relationship between anthropometrics and WCYC with a particular emphasis on its association with course of illness variables. In addition, we were interested whether a subpopulation at heightened risk for cardiovascular disease might be identified on the basis of a biomarker that is associated with cardiovascular disease. We hypothesized that weight cycling is associated with clinical parameters (staging, as number of affective episodes and suicide attempts) anthropometric data and inflammatory markers (ultrasensitive C-reactive protein: hsCRP, interleukin-6: IL-6).

Section snippets

Methods

One hundred and one bipolar individuals were enrolled (52 females). All participants were former in- or outpatients of the department of Psychiatry at the Medical University of Graz (Austria) and were diagnosed with BD according to the DSM-IV criteria. All were euthymic at the time of inclusion and evaluation. All patients (n=101) and controls (n=48) took part in the BIPFAT study that is an ongoing study that broadly aims to characterize various biological markers that subserve the association

Biological assays

Fasting blood samples were collected between 8.00 a.m. and 9.30 a.m. for measuring serum markers and amino acids. Samples were stored at −80 °C. Interleukin-6 was analyzed by an electrochemiluminescence immunoassay (Roche Diagnostics, Germany). Ultrasensitive-CRP (hsCRP) was analyzed with a Tina-quant® C-reactive protein latex ultrasensitive assay (Roche Diagnostics, Germany).

The study was approved by the local ethics committee (Medical University of Graz, Austria) in compliance with the current

Statistics

For statistical analyses IBM Statistics SPSS version 20.0 was used. Normal distributions of data sets were verified using the Kolmogorov–Smirnov test. Multivariate analyses of covariance were conducted to determine differences between WCYC and non-WCYC for IL 6, hsCRP, staging, number of depressive and manic episodes. Because of the multiple comparisons performed, P-values were corrected according to Bonferroni. Pearson correlations (and partial correlations corrected for age) were used to

Results

  • 1.

    There was a significant difference in the amount of WCYC between BD individuals and controls (30% vs. 16%; F=12.970, P=.000).

  • 2.

    We found significant increased BMI and waist to WHtR and a tendency in WHR in WCYC compared to non-WCYC (Multivariate results F(3,91)=2.630, P=.055; controlled for age, see Table 1).

  • 3.

    There was a significant difference between individuals with BD with a history of WCYC compared to non-WCYC in the number of affective episodes independent of age, illness duration and BMI (see

Discussion

To our knowledge, this is the first report about WCYC in individuals with BD. We found significant higher WCYC in our cohort of euthymic individuals with BD compared to healthy controls. The anthropometric profile differed markedly between WCYC and non-WCYC individuals with BD. Compared to non-WCYC individuals with BD, subjects with BD with a history of WCYC had a significant higher number of depressive and manic episodes together with significant higher levels of the inflammatory cytokine IL6

Limitations

First, our study included a small control group with very few WCYC individuals making more detailed statistical analyses impossible. Second, the group of severe WCYC individuals with BD (loosing at least 9 kg for at least three times) was very small, impairing further analysis as regards different WCYC severity grades. Third, patients were not free from medication and other health conditions (except known active cancer), as it was a naturalistic study. Fourth, WCYC was evaluated by a personal

Conclusion

Our results confirm the association between high BMI and WCYC. Importantly, they also give evidence of a link between WCYC and inflammatory pathways—possibly associated with the development of atherosclerosis and cardiovascular disease. More specifically, WCYC in BD was associated with a higher number of episodes which further points to increased inflammation presumably accelerating the development of medical co-morbidities in individuals.

The finding of elevated pro-inflammatory cytokines in

Role of funding source

The pilot study was funded by the “Stadt Graz (A27229000041)” (Project: “Fettstoffwechselstörungen und anthropometrische Besonderheiten bei PatientInnen mit bipolarer affektiver Störung”).

Conflict of interest

ALL authors disclose that there is NO actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence, the work of this paper.

Acknowledgments

We thank our students (in alphabetical order: Filic K, Kattnig F, Leopold S, Mitteregger A, Oberreither EM, Queissner R) and the staff of the University clinic of psychiatry in Graz for their efforts in the study. Particularly we thank all patients with BD and controls for their attendance, time and patience while taking part in this study.

References (52)

  • C.Y. Yim et al.

    The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

    Eur. Psychiatry

    (2012)
  • E.K. Anderson et al.

    Weight cycling increases T-cell accumulation in adipose tissue and impairs systemic glucose tolerance

    Diabetes

    (2013)
  • S. Barbosa-da-Silva et al.

    Weight cycling enhances adipose tissue inflammatory responses in male mice

    PLoS One

    (2012)
  • S.J. Bartlett et al.

    Psychosocial consequences of weight cycling

    J. Consult. Clin. Psychol.

    (1996)
  • S.N. Blair et al.

    Body weight change, all-cause mortality, and cause-specific mortality in the Multiple Risk Factor Intervention Trial

    Ann. Intern. Med.

    (1993)
  • R. Cancello et al.

    Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss

    Diabetes

    (2005)
  • M. De Hert et al.

    Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring an treatment guidelines, plus recommendations at the system and individual level

    World Psychiatry

    (2011)
  • V.A. Diaz et al.

    The association between weight fluctuation and mortality: results from a population-based cohort study

    J. Community Health

    (2005)
  • A. Fagiolini et al.

    Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians

    Bipolar Disord.

    (2005)
  • A.E. Field et al.

    Weight cycling, weight gain, and risk of hypertension in women

    Am. J. Epidemiol.

    (1999)
  • G.D. Foster et al.

    Psychological effects of weight loss and regain: a prospective evaluation

    J. Consult. Clin. Psychol.

    (1996)
  • M.T. Guagnano et al.

    Weight fluctuations could increase blood pressure in android obese women

    Clin. Sci.

    (1999)
  • M.T. Guagnano et al.

    Risk factors for hypertension in obese women. The role of weight cycling

    Eur. J. Clin. Nutr.

    (2000)
  • P. Hamm et al.

    Large fluctuations in body weight during young adulthood and twenty-five-year risk of coronary death in men

    Am. J. Epidemiol.

    (1989)
  • F. Kapczinski et al.

    Clinical implications of a staging model for bipolar disorders

    Expert Rev. Neurother.

    (2009)
  • D.J. Kupfer

    The increasing medical burden in bipolar disorder

    J. Am. Med. Assoc.

    (2005)
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