EMPIRICAL ARTICLE
Are There Common Familial Influences for Major Depressive Disorder and an Overeating–Binge Eating Dimension in both European American and African American Female Twins? Melissa A. Munn-Chernoff, PhD1,2* Julia D. Grant, PhD1,2 Arpana Agrawal, PhD1,2 Rachel Koren, BA3 Anne L. Glowinski, MD, MPE1,2 Kathleen K. Bucholz, PhD1,2 Pamela A.F. Madden, PhD1,2 Andrew C. Heath, DPhil1,2 Alexis E. Duncan, PhD, MPH1,2,4
ABSTRACT Objective: Although prior studies have demonstrated that depression is associated with an overeating–binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the cooccurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups. Method: Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the SemiStructured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age.
Accepted 11 March 2014 Supported by: AA09022, AA07728, AA11998, AA12640, AA17688, and AA17915 from the National Institute of Alcohol Abuse and Alcoholism, by DA019951, DA14363 from the National Institute of Drug Abuse and by HD49024 from the National Institute of Child Health and Human Development. Dr. Munn-Chernoff was supported by training grant T32 AA07580 (Dr. Heath) and Dr. Agrawal received funding from ABMRF/The Foundation for Alcohol Research. The authors report no other conflicts of interest. *Correspondence to: Melissa A. Munn-Chernoff; Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110. E-mail: [email protected] 1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 2 Midwest Alcoholism Research Center, Washington University School of Medicine, St. Louis, Missouri 3 Genetic Alliance, Washington, DC 4 George Warren Brown School of Social Work, Washington University, St. Louis, Missouri Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/eat.22280 C 2014 Wiley Periodicals, Inc. V
International Journal of Eating Disorders 00:00 00–00 2014
Results: The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg 5 .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re 5 .26 [.09, .42]). Discussion: Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD C 2014 and OE-BE across these groups. V Wiley Periodicals, Inc. Keywords: race/ethnicity; African American; twins; major depression; overeating; binge eating (Int J Eat Disord 2014; 00:000–000)
Introduction Previous research has indicated that Major Depressive Disorder (MDD) is associated with eating disorders1–3 and specific eating disorder symptoms, including binge eating (BE)4—a symptom that cuts across eating disorder diagnoses and can be present among individuals who overeat. MDD and BE co-occur more often than by chance alone. Participants in the National Comorbidity Study Replication who reported any lifetime BE were nearly twice as likely to meet criteria for lifetime MDD as those who did not report lifetime BE.1 Further, higher rates of depression have been reported among individuals who meet diagnostic criteria for Binge Eating Disorder compared with individuals who do not.5 Both traits are attributable to a combination of genetic and environmental factors 1
MUNN-CHERNOFF ET AL.
among women, with a heritability estimate of roughly 40% for MDD6 and approximately 50% for BE.7 Thus, given that MDD and BE often co-occur and are both heritable, it is important to consider that they could share a portion of their genetic or environmental risk. Interestingly, few studies have attempted to identify possible genetic and environmental overlap among these or related traits, yielding mixed results. Walters et al.8 reported a moderate genetic correlation (rg 5 .46) between MDD and Bulimia Nervosa, an eating disorder that includes BE. In a study investigating genetic and environmental contributions to six different psychiatric disorders— including MDD and Bulimia Nervosa—in adult female twins, Kendler et al.9 found shared genetic factors across Bulimia Nervosa, Phobia, and Panic Disorder, but not MDD, as well as a shared environmental factor specific to Bulimia Nervosa. In contrast, others10 have found genetic influences that are common across eating problems (i.e., Bulimia Nervosa symptoms) and depression symptoms among girls in both early (i.e., 8–13 year olds) and late (i.e., 14–17 year olds) adolescence, in addition to genetic influences that are specific to eating problems in early adolescence. Overlapping shared environmental factors for depression symptoms and eating problems were also present. Finally, Slane et al.11 reported a large genetic correlation (rg 5 .70) between continuous measures of depressive symptoms and general disordered eating characteristics, which included BE, in a small sample of young adult women (n 5 292 twins). Notably, there have been no twin studies investigating overlapping etiologic factors for MDD and Binge Eating Disorder. The heterogeneity in findings could be due to the age differences across samples, the use of disorder symptoms versus clinical diagnoses, differences in diagnoses examined, and relatedly, the use of continuous versus categorical variables. The specific examination of common familial factors underlying the comorbidity of categorical MDD and overeating, which may include BE, has not been previously published. Much of what is known about genetic and environmental influences on psychopathology, including the sources of covariation between MDD and BE, comes from samples of primarily European ancestry, which is in part due to the low number of non-Caucasian individuals in most major twin studies. A notable exception is a study by Whitfield et al.12 which reported that additive genetic effects accounted for 40% of the overall liability to past week depressive symptoms, with non-shared environmental effects accounting for the remaining 2
variance among African American (AA) male and female twin pairs in middle adulthood (mean age 5 47.1 years). Unfortunately, studies that have investigated genetic and environmental effects on overeating/BE, or the extent to which its genetic and environmental risk is shared with MDD, have not examined AA individuals separately. Therefore, it is unknown whether the magnitude of overlapping genetic and environmental effects for MDD and overeating/BE is similar in European American (EA) and AA women. This is important to consider given that in non-twin populations, prior studies have reported lower rates of MDD in AA compared with EA individuals,13–15 lower,16 similar,17 or higher18,19 rates of BE for AA compared with EA women, and lower20 or higher19 rates of Binge Eating Disorder in AA than EA women. Differences in the prevalence of MDD and overeating/BE between racial/ethnic groups could result from differences in environmental factors known to be associated with these phenotypes. Any differences in etiologic underpinnings may affect the relative contribution of genetic and environmental risk, as well as the correlations, for MDD and overeating/BE. Thus, examining genetic and environmental risks on these phenotypes could yield important information to guide the tailoring of prevention and treatment of MDD, overeating/BE, and their cooccurrence in individuals across racial/ethnic groups. The current study uses a population-based sample of EA and AA young adult female twins to investigate: 1) genetic and environmental influences on MDD and an overeating-binge eating dimension (OE-BE); 2) whether there are overlapping genetic and environmental influences for MDD and OE-BE within each racial/ethnic group; and 3) whether the magnitude of these specific and overlapping influences are the same in EA and AA women. Examining specific eating disorder symptoms, such as overeating/BE, in addition to clinical eating disorders, will help determine whether these symptoms that can cut across diagnoses and predict the later development of eating disorders21 show the same magnitude of genetic and environmental correlations as previous studies examining MDD and eating disorders.
Method Participants Participants were part of the Missouri Adolescent Female Twin Study (MOAFTS),22,23 a population-based longitudinal twin study of female twins identified from International Journal of Eating Disorders 00:00 00–00 2014
DEPRESSION, OVEREATING-BINGE EATING, AND RACE/ETHNICITY
state birth records and born between July 1, 1975 and June 30, 1985 in Missouri to a mother who was a state resident. Twins were recruited using a cohort sequential sampling design. Importantly, the MOAFTS sample is demographically representative of the Missouri population at the time the twins were born, with nearly 15% of twins being AA and the remainder being of European descent (as reported by the mother at the time of birth). A baseline interview was conducted with the twins beginning in 1995 (median age 5 15 years). When possible, interviews were also conducted with at least one parent (usually the mother) at the time the twins entered the study. Zygosity was determined by standard questions24 that have shown approximately 95% agreement with genotyping methods.25 The Wave 4 young adult follow-up interview was conducted an average of 6 years after the baseline assessment (median age 5 22 years). Since all members of the target cohort were 18 years old or older and study participation was no longer contingent upon parental consent, all individuals from the original sampling frame were invited to participate, even if they had not participated at baseline. The only twins who were excluded from being recontacted were those individuals who had either themselves refused future contact or whose parents had refused all future contact with family members. Analyses were conducted on 3,226 EA twins (1,514 complete pairs, 56.3% monozygotic (MZ)) and 550 AA twins (254 complete pairs, 43.7% MZ) who completed the Wave 4 assessment, out of a total of 3,998 EA twins (1,999 pairs) and 740 AA twins (370 pairs) originally identified from birth records. Thus, 81% of EA and 74% of AA respondents from the original sampling frame were included in the current analyses. A summary of response rates is provided elsewhere.26 The protocol was approved by the Washington University School of Medicine Institutional Review Board, and all twins gave informed consent before study participation. Measures At the Wave 4 follow-up, a telephone interview using an adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA)27 assessed DSM-IV lifetime criteria of psychopathology, including MDD and OE-BE. In the depression section, respondents who reported ever experiencing dysphoria, anhedonia, and/or irritability (if
Are There Common Familial Influences for Major Depressive Disorder and an Overeating–Binge Eating Dimension in both European American and African American Female Twins? Melissa A. Munn-Chernoff, PhD1,2* Julia D. Grant, PhD1,2 Arpana Agrawal, PhD1,2 Rachel Koren, BA3 Anne L. Glowinski, MD, MPE1,2 Kathleen K. Bucholz, PhD1,2 Pamela A.F. Madden, PhD1,2 Andrew C. Heath, DPhil1,2 Alexis E. Duncan, PhD, MPH1,2,4
ABSTRACT Objective: Although prior studies have demonstrated that depression is associated with an overeating–binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the cooccurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups. Method: Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the SemiStructured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age.
Accepted 11 March 2014 Supported by: AA09022, AA07728, AA11998, AA12640, AA17688, and AA17915 from the National Institute of Alcohol Abuse and Alcoholism, by DA019951, DA14363 from the National Institute of Drug Abuse and by HD49024 from the National Institute of Child Health and Human Development. Dr. Munn-Chernoff was supported by training grant T32 AA07580 (Dr. Heath) and Dr. Agrawal received funding from ABMRF/The Foundation for Alcohol Research. The authors report no other conflicts of interest. *Correspondence to: Melissa A. Munn-Chernoff; Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110. E-mail: [email protected] 1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 2 Midwest Alcoholism Research Center, Washington University School of Medicine, St. Louis, Missouri 3 Genetic Alliance, Washington, DC 4 George Warren Brown School of Social Work, Washington University, St. Louis, Missouri Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/eat.22280 C 2014 Wiley Periodicals, Inc. V
International Journal of Eating Disorders 00:00 00–00 2014
Results: The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg 5 .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re 5 .26 [.09, .42]). Discussion: Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD C 2014 and OE-BE across these groups. V Wiley Periodicals, Inc. Keywords: race/ethnicity; African American; twins; major depression; overeating; binge eating (Int J Eat Disord 2014; 00:000–000)
Introduction Previous research has indicated that Major Depressive Disorder (MDD) is associated with eating disorders1–3 and specific eating disorder symptoms, including binge eating (BE)4—a symptom that cuts across eating disorder diagnoses and can be present among individuals who overeat. MDD and BE co-occur more often than by chance alone. Participants in the National Comorbidity Study Replication who reported any lifetime BE were nearly twice as likely to meet criteria for lifetime MDD as those who did not report lifetime BE.1 Further, higher rates of depression have been reported among individuals who meet diagnostic criteria for Binge Eating Disorder compared with individuals who do not.5 Both traits are attributable to a combination of genetic and environmental factors 1
MUNN-CHERNOFF ET AL.
among women, with a heritability estimate of roughly 40% for MDD6 and approximately 50% for BE.7 Thus, given that MDD and BE often co-occur and are both heritable, it is important to consider that they could share a portion of their genetic or environmental risk. Interestingly, few studies have attempted to identify possible genetic and environmental overlap among these or related traits, yielding mixed results. Walters et al.8 reported a moderate genetic correlation (rg 5 .46) between MDD and Bulimia Nervosa, an eating disorder that includes BE. In a study investigating genetic and environmental contributions to six different psychiatric disorders— including MDD and Bulimia Nervosa—in adult female twins, Kendler et al.9 found shared genetic factors across Bulimia Nervosa, Phobia, and Panic Disorder, but not MDD, as well as a shared environmental factor specific to Bulimia Nervosa. In contrast, others10 have found genetic influences that are common across eating problems (i.e., Bulimia Nervosa symptoms) and depression symptoms among girls in both early (i.e., 8–13 year olds) and late (i.e., 14–17 year olds) adolescence, in addition to genetic influences that are specific to eating problems in early adolescence. Overlapping shared environmental factors for depression symptoms and eating problems were also present. Finally, Slane et al.11 reported a large genetic correlation (rg 5 .70) between continuous measures of depressive symptoms and general disordered eating characteristics, which included BE, in a small sample of young adult women (n 5 292 twins). Notably, there have been no twin studies investigating overlapping etiologic factors for MDD and Binge Eating Disorder. The heterogeneity in findings could be due to the age differences across samples, the use of disorder symptoms versus clinical diagnoses, differences in diagnoses examined, and relatedly, the use of continuous versus categorical variables. The specific examination of common familial factors underlying the comorbidity of categorical MDD and overeating, which may include BE, has not been previously published. Much of what is known about genetic and environmental influences on psychopathology, including the sources of covariation between MDD and BE, comes from samples of primarily European ancestry, which is in part due to the low number of non-Caucasian individuals in most major twin studies. A notable exception is a study by Whitfield et al.12 which reported that additive genetic effects accounted for 40% of the overall liability to past week depressive symptoms, with non-shared environmental effects accounting for the remaining 2
variance among African American (AA) male and female twin pairs in middle adulthood (mean age 5 47.1 years). Unfortunately, studies that have investigated genetic and environmental effects on overeating/BE, or the extent to which its genetic and environmental risk is shared with MDD, have not examined AA individuals separately. Therefore, it is unknown whether the magnitude of overlapping genetic and environmental effects for MDD and overeating/BE is similar in European American (EA) and AA women. This is important to consider given that in non-twin populations, prior studies have reported lower rates of MDD in AA compared with EA individuals,13–15 lower,16 similar,17 or higher18,19 rates of BE for AA compared with EA women, and lower20 or higher19 rates of Binge Eating Disorder in AA than EA women. Differences in the prevalence of MDD and overeating/BE between racial/ethnic groups could result from differences in environmental factors known to be associated with these phenotypes. Any differences in etiologic underpinnings may affect the relative contribution of genetic and environmental risk, as well as the correlations, for MDD and overeating/BE. Thus, examining genetic and environmental risks on these phenotypes could yield important information to guide the tailoring of prevention and treatment of MDD, overeating/BE, and their cooccurrence in individuals across racial/ethnic groups. The current study uses a population-based sample of EA and AA young adult female twins to investigate: 1) genetic and environmental influences on MDD and an overeating-binge eating dimension (OE-BE); 2) whether there are overlapping genetic and environmental influences for MDD and OE-BE within each racial/ethnic group; and 3) whether the magnitude of these specific and overlapping influences are the same in EA and AA women. Examining specific eating disorder symptoms, such as overeating/BE, in addition to clinical eating disorders, will help determine whether these symptoms that can cut across diagnoses and predict the later development of eating disorders21 show the same magnitude of genetic and environmental correlations as previous studies examining MDD and eating disorders.
Method Participants Participants were part of the Missouri Adolescent Female Twin Study (MOAFTS),22,23 a population-based longitudinal twin study of female twins identified from International Journal of Eating Disorders 00:00 00–00 2014
DEPRESSION, OVEREATING-BINGE EATING, AND RACE/ETHNICITY
state birth records and born between July 1, 1975 and June 30, 1985 in Missouri to a mother who was a state resident. Twins were recruited using a cohort sequential sampling design. Importantly, the MOAFTS sample is demographically representative of the Missouri population at the time the twins were born, with nearly 15% of twins being AA and the remainder being of European descent (as reported by the mother at the time of birth). A baseline interview was conducted with the twins beginning in 1995 (median age 5 15 years). When possible, interviews were also conducted with at least one parent (usually the mother) at the time the twins entered the study. Zygosity was determined by standard questions24 that have shown approximately 95% agreement with genotyping methods.25 The Wave 4 young adult follow-up interview was conducted an average of 6 years after the baseline assessment (median age 5 22 years). Since all members of the target cohort were 18 years old or older and study participation was no longer contingent upon parental consent, all individuals from the original sampling frame were invited to participate, even if they had not participated at baseline. The only twins who were excluded from being recontacted were those individuals who had either themselves refused future contact or whose parents had refused all future contact with family members. Analyses were conducted on 3,226 EA twins (1,514 complete pairs, 56.3% monozygotic (MZ)) and 550 AA twins (254 complete pairs, 43.7% MZ) who completed the Wave 4 assessment, out of a total of 3,998 EA twins (1,999 pairs) and 740 AA twins (370 pairs) originally identified from birth records. Thus, 81% of EA and 74% of AA respondents from the original sampling frame were included in the current analyses. A summary of response rates is provided elsewhere.26 The protocol was approved by the Washington University School of Medicine Institutional Review Board, and all twins gave informed consent before study participation. Measures At the Wave 4 follow-up, a telephone interview using an adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA)27 assessed DSM-IV lifetime criteria of psychopathology, including MDD and OE-BE. In the depression section, respondents who reported ever experiencing dysphoria, anhedonia, and/or irritability (if
