Research reportWeight cycling in bipolar disorder
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.
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