gender-specific lipid profiles in patients with bipolar disorder

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    Keywords:DyslipidemiaBipolar disorderGenderInsulin resistanceMetabolic


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    lipoprotein (LDL) cholesterol, triglycerides (TG), and high-densitylipoprotein cholesterol (HDL) are independent risk factors forcoronary heart disease (CHD) (NCEP, 2002). LDL remains theprimary treatment target of the National Cholesterol EducationProgram (NCEP) Adult Treatment Protocol (ATP) III (NCEP, 2002).

    et al., 1991; Williams, 2004). These gender differences in lipidsappear to be highly correlated with age and abdominal obesity(Gostynski et al., 2004; Seidell et al., 1991). In the U.S., genderdifferences in lipid distribution appear to be changing. NationalHealth and Nutrition Examination Survey (NHANES) 2003e2006data showed a higher prevalence of lipid abnormalities in womenversus men (American Heart Association, 2010; Regitz-Zagroseket al., 2007), possibly driven by increasing obesity in women(Regitz-Zagrosek et al., 2007). Gender differences in lipids are

    * Corresponding author. Tel.: 1 650 725 1774; fax: 1 650 724 9900.

    Contents lists availab

    Journal of Psych


    Journal of Psychiatric Research 45 (2011) 1036e1041E-mail address: (M. Vemuri).patients with bipolar disorder (BD) (Fagiolini et al., 2005;Fiedorowicz et al., 2008; Garcia-Portilla et al., 2008; Kilbourneet al., 2004; Sicras et al., 2008; Van Winkel et al, 2008), all ofwhich are modiable risk factors for cardiovascular disease (CVD)(Newcomer, 2009).

    Evaluating dyslipidemia is a component of routine medicationmonitoring in BD, and thus places the treating psychiatrist in theposition of identifying modiable risk factors for CVD. Low-density

    dyslipidemia, and possibly mood disorders (NCEP, 2002; Rasgonand Jarvik, 2004; Rasgon et al., 2002).

    In the general population, women compared to men havehistorically lived longer, developed cardiovascular disease at anolder age, and had more favorable lipid proles (Regitz-Zagroseket al., 2007). Internationally, women compared to men consis-tently have more favorable lipid proles, lower TC, LDL, TG andhigher HDL (Gardner et al., 2000; Gostynski et al., 2004; Seidell1. Introduction

    High rates of metabolic abnormdiabetes, obesity, and the metabol0022-3956/$ e see front matter 2011 Elsevier Ltd.doi:10.1016/j.jpsychires.2011.02.002LDL, HDL, TG) at clinicians discretion, a psychiatry clinic visit within 2 months of laboratory, and werenot medicated for dyslipidemia were included. IR was imputed from TG/HDL ratio.Results: Women, compared with men, had signicantly lower mean triglycerides (105.58 64.12 vs.137.99 105.14, p 0.009), higher mean HDL cholesterol (60.17 17.56 vs. 46.07 11.91 mg/dl,p < 0.001), lower mean LDL cholesterol (109.84 33.47 vs. 123.79 35.96 mg/dl, p 0.004), and lowerTG/HDL ratio (1.98 1.73 vs. 3.59 3.14 p < 0.001). Compared to men, women had a signicantly lowerprevalence of abnormal total cholesterol, LDL, TG, HDL, and TG/HDL ratio. No signicant differences werefound between men and women with regard to age, BMI, ethnicity, educational attainment, smokinghabits, bipolar illness type, illness severity or duration, or weight-liable medication exposure.Discussion: In outpatients with BD, women had more favorable lipid proles than men despite similardemographic variables. This sample of primarily Caucasian and educated patients, receiving vigilantclinical monitoring, may represent a relatively healthy psychiatric population demonstrating genderdifferences similar to those in the general population.

    2011 Elsevier Ltd. All rights reserved.

    such as dyslipidemia,rome (MetS) occur in

    The ratio of TG to HDL cholesterol (TG/HDL) has been proposed asa proxy marker of insulin resistance (IR) (McLaughlin et al., 2005),a condition in which tissue responsiveness to the normal action ofinsulin is impaired, and is related to the development of diabetes,Accepted 4 February 2011

    ment. BD patients (n 234; 61% female; 42% Type I, 47% Type II, 11% NOS) with a mean age of 40.3 14.0years, mean BMI 26.8 6.4, and 81% Caucasian, who had one of four lipid measures (total cholesterol,31 January 2011 2000 and 2007 were evaluated. Patients were followed longitudinally and received naturalistic treat-Gender-specic lipid proles in patients

    Mytilee Vemuri*, Heather A. Kenna, Po W. Wang, TDepartment of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Roa

    a r t i c l e i n f o

    Article history:Received 15 April 2010Received in revised form

    a b s t r a c t

    Objective: High rates of dydisorder (BD). We assessedMethods: Data from 491 ou

    journal homepage: www.eAll rights reserved.ith bipolar disorder

    ence A. Ketter, Natalie L. Rasgontanford, CA 94305-5723, United States

    idemia and insulin resistance (IR) are reported in patients with bipolarnder effects upon rates of dyslipidemia/IR in outpatients with BD.tients (ages 18e88) seen in the Stanford Bipolar Disorders clinic between

    le at ScienceDirect

    iatric Research

    vier .com/locate/psychires

  • iatriattributed to sex steroid hormone inuence on lipids and on sexdifferences in fat distribution; specically abdominal fat tissue ismore abundant in men compared to premenopausal womenfavoring development of insulin resistance (IR), dyslipidemia andhypertension (Regitz-Zagrosek et al., 2007). After menopause,lipoprotein concentrations and fat distribution shift to a more malepattern (Ley et al., 1992).

    In contrast to gender differences in the general population,women in psychiatric populations appear to have higher rates ofmodiable CVD risk factors, such as obesity (Wang et al., 2006) andMetS (McEvoy et al., 2005; Teixeira and Rocha, 2007), relative tomen, suggesting substantive vulnerability to CVD and its riskfactors in women with mental illness. While women with BDhave high rates of dyslipidemia (Stemmle et al., 2009), genderdifferences in dyslipidemia have not been well characterized inpsychiatric populations. In this study, we compared lipid valuesbetween female and male outpatients with bipolar disorder (BD).Given existing published data suggesting women with mentalillness have a higher vulnerability to CVD and its risk factors, wehypothesized that women with BD would have less favorable lipidproles than men.

    2. Methods

    The study was approved by the Stanford University Adminis-trative Panel on Human Subjects, and patients provided verbal andwritten informed consent prior to participation. Data wereanalyzed from all outpatients (age 18e88) seen in the Stanfordoutpatient Bipolar Disorders clinic between January 2000 and June2007 who had consented to longitudinal data review of theirmedical records and who were seen for ongoing evaluation. Indi-viduals seen for one-time consultations were not included. A totalof 491 patient records were reviewed. Patients were included inanalysis (n 234) if the following criteria were met: a) patient metDSM-IV diagnostic criteria for bipolar disorder b) patient receivedone of four concurrent lipid measures within twomonths of a clinicvisit including: Total cholesterol (TC) (n 256), Triglycerides (TG)(n 253), Low-Density Lipoprotein (LDL) (n 238), High-DensityLipoprotein (HDL) (n 250), and c) were not concurrently treatedwith lipid-lowering medications. In this sample, neither genderwas signicantly more likely to be treated with a lipid-loweringmedication (c2 2.05, p 0.152), nor were there signicantdifferences in lipid values by gender within the 22 patients treatedwith lipid-lowering medication.

    2.1. Intake evaluations and clinical follow-up

    Baseline clinical evaluations were performed using theSystematic Treatment Enhancement Program for Bipolar Disorder(STEP-BD) Affective Disorders Evaluation (ADE) (Sachs et al., 2003)to establish psychiatric diagnosis of BD, and to derive clinicalinformation including age, current and previous medication treat-ment, years since rst episode, bipolar illness type, and height.Demographic information, including self-reported gender, race,and education attainment was collected by patient self-assess-ments and interview. Patients received naturalistic treatmentguided by model practice procedures, which included publishedpharmacotherapy guidelines (Dennehy et al., 2007). Clinical infor-mation, including psychotropic treatment, weight, and illnessseverity, measured by Clinical Global Inventory (CGI), was longi-tudinally collected using STEP-BD Clinical Monitoring Form (CMF)(Sachs et al., 2002).

    For analytic purposes, patients were classied into three medi-cation categories based on the medication taken at time of veni-

    M. Vemuri et al. / Journal of Psychpuncture: 1) weight-liable mood stabilizer/antipsychotic (i.e.associated with substantive weight-gain risk): lithium (Bowdenet al., 2000), valproate (Bowden et al., 2000), oxcarbazepine(Vieta et al., 2008), olanzapine (Tohenet al., 2006), clozapine (Allisonet al., 1999), quetiapine (Weisler et al., 2009), risperidone (Quirozet al., 2010), or aripiprazole (Keck et al., 2006); 2) non-weight-liable mood stabilizer/antipsychotic (associated with non-substan-tive weight-gain risk): lamotrigine (Sachs et al., 2006), ziprasidone(Bowden et al., 2009) or carbamazepine (Weisler et al., 2006), or 3)no mood stabilizer/antipsychotic. Only second-generation antipsy-chotics, if any, were received by patients in the present analysis.Patients were only included in a mood stabilizer/antipsychoticcategory if they had been treated for aminimum of sixmonths withthe above mentioned medication classes. If patients were concur-rently treated with both weight-liable and non-weight-liablemedications, they were included in the weight-liable group.

    2.2. Assessment of lipids and metabolic function

    Fasting blood lipid panels and thyroid function laboratorieswere obtained at clinician discretion