Letter to the editorInsulin resistance and hyperlipidemia in women with bipolar disorder
Introduction
We previously reported high rates of metabolic abnormalities in women with bipolar disorder (BD) (Rasgon et al., 2005, Rasgon et al., 2000, Rasgon et al., 2002). However, results were limited as all subjects were receiving mood stabilizer (MS) treatment at the time of evaluation.
Valproate and other MS are associated with hyperinsulinemia and dyslipidemia (Isojärvi et al., 1998, Isojärvi and Tapanainen, 2000, Isojärvi et al., 2001, Vainionpää et al., 1999). Among plausible mechanisms, weight gain associated with these agents and obesity are the main culprits. Obesity is correlated with insulin resistance (IR) and dyslipidemia (Abbasi et al., 2002). However, lean individuals can also exhibit IR and dyslipidemia (Abbasi et al., 2002), which are independent risk factors for cardiovascular disease and type II diabetes (Carlson et al., 1979, Castelli et al., 1986, Hokanson and Austin, 1996, Miller and Miller, 1975). Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and their ratio (TG/HDL-C), are proven surrogate biomarkers of IR in non-diabetic patients (McLaughlin et al., 2003, McLaughlin et al., 2005).
The goal of this study was to examine metabolic profiles of women with bipolar II disorder (BDII), who were not receiving MS treatment at the time of evaluation.
Section snippets
Methods
The Stanford University Administrative Panel on Human Subjects approved this study, and all subjects provided verbal and written informed consent. The current study was a satellite of a study of the efficacy of Depakote-ER™ in the treatment of BDII. Inclusion and exclusion criteria were discussed elsewhere. Fasting morning blood samples were taken prior to the start of treatment with valproate.
Data analysis
Two-tailed t-tests (p < 0.05) were conducted to determine whether lipid values varied based on previous use of MS. We performed an analysis of covariance on lipid values, with body mass index (BMI) as the covariate, and past MS usage as the predictor. As this was an exploratory analysis, we did not correct for multiple comparisons.
Clinical characteristics
Eleven women participated in the study. They ranged in age from 27 to 47 years [35.6 ± 6.4]. All women were diagnosed with BDII and were currently depressed at the time of evaluation. Clinical characteristics are presented in Table 1. None were previously treated with valproate prior to study participation. Eight women were completely MS naive (e.g. they had no prior exposure to lithium, atypical antipsychotics, lamotrigine, valproate, and/or carbamazepine). Two women had previously been exposed
Discussion
This is the first report, to our knowledge, of metabolic profiles in untreated women with BD. The main findings of this pilot study were increased BMI, IR, and hyperlipidemia in an untreated sample of depressed women with BDII. These findings are in agreement with our own previous studies of women with BD (Rasgon et al., 2005, Rasgon et al., 2000, Rasgon et al., 2003), and other published data (Elmslie et al., 2000, Fagiolini et al., 2002, Fagiolini et al., 2005). The present study extends our
Limitations
The main limitation of this study is the small sample size. With only eleven subjects, the statistical power of the study is small. Not all women in the sample were previously untreated with MS, due to the difficulty of recruiting untreated patients. This allowed for a comparison of metabolic markers between groups, but interpretation obviously is limited by the small cell size (n = 3) for the previously treated group.
Another limitation is the lack of a follow-up evaluation. As part of another
Conflict of interest
Ms. Stemmle, Ms. Kenna, and Ms. Hill do not have any conflict of interests to disclose. Dr. Rasgon has received grant/research support from Abbott, Forest, GlaxoSmithKline, and Wyeth-Ayerst. She is on advisory boards for GlaxoSmithKline and Wyeth-Ayerst, and has received honoraria from Abbott, Bristol Myers Squibb, Forest, GlaxoSmithKline, and Pfizer. Dr. Wang has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Eisai, Elan, Eli Lilly, GlaxoSmithKline, Janssen,
Contributors
Dr. Rasgon designed the study and wrote the protocol. Ms. Kenna managed the literature searches and analyses. Ms. Stemmle undertook the statistical analysis, and wrote the first draft of the manuscript. Ms. Hill was responsible for data collection. Drs. Ketter and Wong were responsible for all patient care. All authors contributed to and have approved the final manuscript.
Role of funding source
The study sponsor did not have any role in study design; in the collection, analysis and/or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Acknowledgements
None.
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