MCTFR Summaries of Research Publication Findings

Commings, D.E., Wu, S., Rostamkhami, N., McGue, M, Iacono, W.G. & MacMurray, J.P. (2002). "Association of the Muscarinic Cholinergic 2 Receptor (CHRM2) Gene with Major Depression." American Journal of Medical Genetics, 114, 527-529.

  • The CHRM2 gene is – already known to be related to sleep and stress – is shown to be associated with depression in women, but not in men.

Niess, M.B., Stevenson, J., Legrand, L.N., Iacono, W.G., & Sedikides, C. (2009). "Self-esteem, negative emotionality, and depression as a common temperamental core." Journal of Personality, 77(2), 327-346. PMCID: PMC2757924

  • This work demonstrates that self-esteem, negative emotionality (sometime called neuroticism), and depression share some common genetic causes, and so could be viewed together as a heritable core temperament. For example, if someone has low self-esteem, they would also be more likely to experience negative emotions; similarly, someone with high self-esteem is apt to be lower in negative emotionality (and also somewhat less likely to be depressed).

Abstracts from Research Publications (chronological)

Holdcraft L.C., Iacono, W.G., & McGue, M.K. (1998). Antisocial personality disorder and depression in relation to alcoholism: A community-based sample. Journal of Studies on Alcohol, 59, 222-226.

  • Objective: Antisocial Personality Disorder (ASPD) and depression frequently co-occur with alcoholism. This study examined the relationship between the presence of ASPD or depression and the course and severity of alcoholism. Method: Alcoholic men (n = 207), recruited from a community-based sample, the Minnesota Twin-Family Study (MTFS), were categorized according to comorbid diagnoses into the following four groups: alcoholics with ASPD (n = 25), alcoholics with depression (n = 24), alcoholics with neither ASPD nor depression, but who were allowed to have additional psychopathology (n = 130) and alcoholics with no other psychiatric diagnoses (n = 28). The four diagnostic subgroups were compared on alcohol and drug use, alcohol-related problems and personality dimensions. Results: ASPD was associated with an earlier age of first intoxication, a more chronic and severe course of alcoholism, more social consequences of drinking and higher levels of drug use. On the whole, depression was associated with a less severe course of alcoholism. Alcoholics with depression and alcoholics with ASPD had higher negative emotionality, and alcoholics with ASPD had lower constraint scores on the Multidimensional Personality Questionnaire. Conclusions: These findings, derived from a community-based sample, indicate the importance of assessing comorbidity among alcoholics and confirm the association of ASPD with a more severe and chronic course of alcoholism and with higher likelihood of drug abuse. (J. Stud. Alcohol 59: 222-226, 1998)

Shiner, R.L. & Marmorstein, N.R. (1998). Family environments of adolescents with lifetime depression: Associations with maternal depression history. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 1152-1160.

  • OBJECTIVE: To assess family functioning of adolescents with a history of depression, taking into account maternal history of depression.  METHOD: Lifetime major depression was assessed with standardized interviews in an epidemiological sample of adolescent twins and their parents. Family members completed questionnaires measuring family functioning. The families of three groups of adolescents were compared: ever-depressed adolescents with ever-depressed mothers (n = 37), ever-depressed adolescents with never-depressed mothers (n = 42), and never-depressed control adolescents (n = 82).  RESULTS: A greater proportion of ever-depressed adolescents had ever-depressed mothers than did control adolescents (47% versus 18%); rates of paternal depression did not differ between the two groups. Ever-depressed adolescents with ever-depressed mothers described poorer family functioning than did ever-depressed adolescents with never-depressed mothers and controls. Relative to control mothers, mothers of both groups of ever-depressed adolescents reported family difficulties, particularly in the father-adolescent relationship. Fathers' descriptions of family relationships did not differ among the three groups. Ever-depressed adolescents came disproportionately from divorced families.  CONCLUSIONS: These results highlight the importance of considering parental depression in the treatment of adolescent depression and underscore the need to understand the interactional patterns in families of depressed youth, particularly those with multiple depressed members.

Krueger, R.F., McGue, M., & Iacono, W.G. (2001). The higher order structure of common DSM mental disorders: Internalization, externalization, and their connections to personality. Personality and Individual Differences, 30, 1245-1259.

  • Comorbidity among mental disorders is commonly observed in clinical and epidemiological samples. Can comorbidity be understood as meaningful covariance, and is this covariance structure linked with personality We addressed this question in a sample of 634 female and 549 male, middle-aged participants in the Minnesota Twin-Family Study (MTFS). Mental disorders were assessed using the Structured Clinical Interview for DSM-III-R. the Substance Abuse Module front the Composite International Diagnostic Interview, and a specially-designed interview for the assessment of antisocial personality disorder. Personality was assessed using the Multidimensional Personality Questionnaire. Relations among symptom scales for eight common DSM disorders were compatible with hypothesized underlying bivariate normal distributions. Polychoric correlations among these scales were well-fit by a two-factor model positing internalizing and externalizing factors, which, in turn, were correlated with broad personality dimensions. Internalizing was positively correlated with negative emotionality (and negatively with positive emotionality in women) and externalizing was negatively correlated with constraint. These findings suggest that internalization, externalization, and their links to personality may provide a useful framework for understanding covariance among common adult mental disorders.

Marmorstein, N.R., & Iacono, W.G. (2001). An investigation of female adolescent twins with both major depression and conduct disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 40, 299-306.

  • OBJECTIVE: Conduct disorder (CD) and major depression (MDD) frequently co-occur in adolescents, but little is known about the characteristics and functioning of youths, especially females, with both disorders. This study describes the functioning of female adolescents with histories of both CD and MDD.  METHOD: Subjects were selected from an epidemiological sample of 17-year-old female twins based on having a lifetime DSM-III-R diagnosis of MDD and/or CD; control subjects had no history of either disorder.  RESULTS: In nearly all domains examined, including measures of academic success (including academic achievement and school adjustment), personality, quality of peer relationships, and high-risk behavior (including substance dependence and early sexual experience), main effects of one or both disorders were found and related to impaired functioning. In addition, interaction effects were found in the areas of substance dependence symptoms (for all classes of substances), negative school-related events, and a personality-based predisposition not to experience positive emotions, indicating that those with both diagnoses were especially impaired.  CONCLUSIONS: In some domains, histories of MDD and CD interact and relate to particularly severe problems. The implications of these findings for research and treatment, including the high likelihood of substance and school adjustment problems in these youths, are discussed.

Comings, D.E., Wu, S., Rostamkhani, M., McGue, M., Iacono, W.G., & MacMurray, J.P. (2002). Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women. American Journal of Medical Genetics (Neuropsychiatric Genetics), 114, 527-529.

  • Cholinergic neurons have been implicated in depression and in the disorders of REM sleep in depression. We examined a common A-> T 1890 polymorphism in the 3' UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene. There was a significant increase in the frequency of 11 homozygotes in 126 women with major depression (43.7%) compared to 304 women without major depression (25.7%), P =.001. There was no increase in the frequency of 11 homozygotes in 52 men with depression (26.9%) compared to 278 men without depression (27.7%). Regression analysis, scoring subjects with the 11 genotype as 1, and those with other genotypes as 0, showed that in women r(2) =.030, F = 13.37, P =.0003. By contrast, in men r(2) =.00001, F = 0.002, P =.96. These results are consistent with a gender-specific role of the CHRM2 gene in depression in women.

Burcusa, S.L., Iacono, W.G., & McGue, M. (2003). Adolescent twins discordant for major depressive disorder: Shared familial liability to externalizing and other internalizing disorders. Journal of Child Psychology and Psychiatry, 44, 997-1005.

  • BACKGROUND: In adolescents, as in adults, there is often comorbidity between major depressive disorder (MDD) and many other disorders. In this study, the discordant twin method was used to investigate whether this comorbidity in adolescents may be due to a shared familial liability between MDD and other internalizing disorders, and between MDD and externalizing disorders. METHODS: We examined prevalence rates of anxiety disorders, substance use disorders, and childhood externalizing disorders in 624 seventeen-year-old same-sex monozygotic and dizygotic twin pairs. Overall prevalence of MDD in this sample was 12.9%. Twenty-seven twin pairs were concordant for MDD, 107 were discordant for MDD, and 490 were concordant for no MDD. RESULTS: Prevalence rates for disorders other than MDD were elevated in the depressed twins relative to the control twins from pairs concordant for no MDD. Prevalence rates were also elevated in the nondepressed co-twins of depressed twins. Twin concordance for disorders other than MDD was higher in twin pairs where at least one twin was depressed than in pairs where neither twin was depressed. CONCLUSIONS: These results support a shared familial liability between MDD and other internalizing disorders and between MDD and externalizing disorders in adolescents.

Comings, D.E., Wu, S., Rostamkani, M., McGue, M., Iacono, W.G., Cheng, L.S-c., & MacMurray, J.P. (2003). Role of the cholinergic muscarinic receptor (CHRM2) gene in cognition. Molecular Psychiatry, 8, 10-13.

  • AB Letter discusses the role of the cholinergic muscarinic 2 receptor (CHRM2) gene in cognition. Identification of a possible role of cholinergic receptor genes in humans has been hampered by the lack of reported polymorphisms. The authors identified a common A->T 1890 polymorphism in the 3'UTR of the CHRM2 gene. To determine if it was associated with IQ, 358 adult males and 470 adult females were examined. The subjects were the parents of twins from the Minnesota Twin and Family Study. All were given the Wechsler Adult Intelligence Scale-Revised. To assess which variable was more closely associated with the CHRM2 gene, a MONOVA was performed using both total IQ and years of education as the dependent variables and the CHRM2 gene as the independent variable for the total set. Long-term potentiation has been implicated in memory and cognition and the CHRM2 plays a role in long-term potentiation in the striatum. This suggests that genetic variants at the CHRM2 gene might be associated with different aspects of cognition. It is suggested that these preliminary results are consistent with a role of the CHRM2 gene in cognitive processes in humans, as assessed by both total IQ and years of education.

Marmorstein, N., & Iacono, W.G. (2003). Major depression and conduct disorder in twins by late adolescence: Functioning and risk for future psychopathology. Journal of the American Academy of Child and Adolescent Psychopathology, 42, 225-233.

  • OBJECTIVE: Major depression (MDD) and conduct disorder (CD) co-occur in adolescents at rates higher than would be expected by chance. This study described the functioning of adolescents with histories of these disorders and examined whether these patterns of association differed by gender. METHOD: Subjects with a lifetime diagnosis of MDD and/or CD were selected from a sample of 17-year-old twins; control subjects had no history of either disorder. The domains of school success, substance dependence, peer relationships, and age of first sexual intercourse were examined. RESULTS: Overall, each disorder separately and especially both disorders together related to increased maladjustment in the domains of school success and substance dependence. For school behavior problems, nicotine dependence, and drug dependence, the combination of MDD and CD related to particularly problematic functioning. Results were similar for males and females. Longitudinal data indicated that the occurrence of these disorders by late adolescence was predictive of subsequent depression and antisocial behavior in early adulthood. CONCLUSIONS: The combination of CD and MDD relates to more serious maladjustment, especially relating to school success and substance dependence, than would be expected given the adjustment associated with each disorder alone.

Marmorstein, N. & Iacono, W.G. (2004). Major depression and conduct disorder in youth: Associations with parental psychopathology and parent child conflict. Journal of Child Psychology & Psychiatry, 45, 377-386.

  • BACKGROUND: This study examined conduct disorder (CD) and major depression (MDD) in adolescents in relationship to parent-child conflict and psychopathology in their parents. METHOD: Participants were drawn from a population-based sample of twins and their families. Affected participants had lifetime diagnoses of CD and/or MDD; controls had no history of either disorder. RESULTS: The presence of CD or MDD in an adolescent was related to increased rates of maternal MDD and paternal antisocial behavior. Both CD and MDD in adolescents were directly associated with high parent-child conflict. This association appeared unrelated to whether the father had a history of antisocial behavior; however, the association between mother-child conflict and psychopathology in the child was related to the mother having a history of MDD as well. CONCLUSION: The implications of these findings for the complex relationship between parental diagnoses, child diagnoses, and parent-child conflict are discussed.

Marmorstein, N.R., Malone, S.M., & Iacono, W.G. (2004). Psychiatric disorders among offspring of depressed mothers: Associations with paternal psychopathology. American Journal of Psychiatry, 161, 1588-1594.

  • OBJECTIVE: The association between maternal depression and offspring dysfunction is well documented; however, little attention has been paid to psychopathology in the partners of these depressed mothers or to how paternal psychopathology might influence the relationship between maternal depression and offspring dysfunction. The purpose of this study was to explore whether major depression and/or antisocial behavior tended to occur more frequently among partners of depressed mothers (compared to partners of nondepressed mothers) and to examine how these paternal disorders related to offspring psychopathology. METHOD: Participants were drawn from the Minnesota Twin Family Study, a community-based study of twins and their parents. Depressed and nondepressed mothers, their partners (the biological fathers of the twins), and their 17-year-old offspring were included. Structured interviews were used to assess participants for the presence of major depression, conduct disorder, and adult antisocial behavior. RESULTS: Depressed mothers tended to partner with antisocial fathers. Depression in mothers and antisocial behavior in fathers were both significantly and independently associated with offspring depression and conduct disorder. No interactions of the parental diagnoses with each other or with the gender of the offspring were found. CONCLUSIONS: Many offspring of depressed mothers experience the additional risk of having an antisocial father. The implications of these findings for risk among the offspring of depressed mothers are discussed.

Burcusa, S.L., & Iacono, W.G. (2007). Risk for recurrence in depression. Clinical Psychology Review, 27, 959-985.

  • Depression is a highly recurrent disorder with significant personal and public health consequences. Prevention of recurrence would be extremely desirable, and thus researchers have begun to identify risk factors that are specific to recurrence, which may be different from risk factors for first-onset of depression. Methodological issues in this area of research are briefly reviewed (e.g., the various definitions of “recurrence” and “depression”), followed by a review of studies on specific risk factors, including demographic variables (gender, socio-economic status, marital status), clinical variables (age at first onset, number of prior episodes, severity of first/index episode, comorbid psychopathology), family history of psychopathology, and psychosocial and psychological variables (level of psychosocial functioning, cognitions, personality, social support, and stressful life events). In addition, scar theories are evaluated for their potential to explain how these variables and recurrent depression are linked. Our review suggests that recurrent depression reflects an underlying vulnerability that is largely genetic in nature and that may predispose those high in the vulnerability not only to recurrent depressive episodes, but also to the significant psychosocial risk factors that often accompany recurrent depression.

Keyes, M.A., Sharma, A., Elkins, I.J., Iacono, W.G., & McGue, M. (2008). The mental health of US adolescents adopted in infancy. Archives of Pediatrics & Adolescent Medicine, 162, 419-425.

  • Objective  To determine whether adopted adolescents are at excess risk for clinically relevant behavioral and emotional problems. Design  We examined whether adopted and nonadopted adolescents differed on quantitative indicators of mental health and the prevalence of childhood disorders and whether differences exist between internationally and domestically placed adoptees. Setting  Assessments occurred at the University of Minnesota from December 11, 1998, to June 4, 2004. Participants  Adolescents adopted in infancy were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadopted adolescents were ascertained from Minnesota birth records. The final sample included these adolescents with their rearing parents. Main Exposure  The main exposure was adoptive status: nonadopted (n = 540), international adoptive placement (n = 514), or domestic adoptive placement (n = 178). Outcome Measures  Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) clinical assessments based on child and parent reports of attention-deficit/hyperactivity, oppositional defiant, conduct, major depressive, and separation anxiety disorders; teacher reports of psychological health; and contact with mental health professionals. Results  Adoptees scored only moderately higher than nonadoptees on quantitative measures of mental health. Nevertheless, being adopted approximately doubled the odds of having contact with a mental health professional (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.48-2.84) and of having a disruptive behavior disorder (OR, 2.34; 95% CI, 1.72-3.19). Relative to international adoptees, domestic adoptees had higher odds of having an externalizing disorder (OR, 2.60; 95% CI, 1.67-4.04). Conclusions  Moderate mean differences in quantitative indicators of mental health can lead to substantial differences in disorder prevalence. Although most adopted adolescents are psychologically healthy, they may be at elevated risk for some externalizing disorders, especially among those domestically placed.

Marmorstein, N.R., von Ranson, K.M., Iacono, W.G., & Malone, S.M. (2008). Prospective associations between depressive symptoms and eating disorder symptoms among adolescent girls. International Journal of Eating Disorders, 41, 118-123.

  • OBJECTIVE: Although eating disorders are frequently associated with depression, evidence regarding which problem predicts the other is conflicting, and little research has addressed the developmental course of this relation. This study examined longitudinal associations between depression and eating pathology across adolescence. METHOD: Participants were 754 girls participating in the community-based Minnesota Twin Family Study. Depressive symptoms and eating pathology were assessed at approximately ages 11, 14, and 17. RESULTS: As expected, substantial continuity in both eating pathology and depressive symptoms occurred across time. Analysis of cross-lag paths controlling for earlier levels of symptoms indicated that overall levels of eating pathology predicted later depressive symptoms from 11 to 14 and from 14 to 17. CONCLUSION: Adolescent girls with high levels of eating-related pathology appear to be at risk for later depression.

Tully, E.C., Iacono, W.G., & McGue, M. (2008). An adoption study of parental depression as an environmental liability for adolescent depression and childhood disruptive disorders. American Journal of Psychiatry, 165(9): 1148-1154. PMCID: PMC2573034

  • OBJECTIVE: The authors used an adoption study design to investigate environmental influences on risk for psychopathology in adolescents with depressed parents. METHOD: Participants were 568 adopted adolescents ascertained through large adoption agencies, 416 nonadopted adolescents ascertained through birth records, and their parents. Clinical interviews with parents and adolescents were used to determine lifetime DSM-IV-TR diagnoses of major depressive disorder, oppositional defiant disorder, conduct disorder, attention deficit hyperactivity disorder (ADHD), and substance use disorders in adolescents and major depression in mothers and fathers. Effects of parental depression (either parent with major depression, maternal major depression, and paternal major depression) on adolescent psychopathology were tested in nonadopted and adopted adolescents separately, and interactive effects of parental depression and adoption status were tested. RESULTS: Either parent having major depression and a mother having major depression were associated with a significantly greater risk for major depression and disruptive behavior disorders in both nonadopted and adopted adolescents. Paternal depression did not have a main effect on any psychiatric disorder in adolescents and, with one exception (ADHD in adopted adolescents), did not predict significantly greater likelihoods of disorders in either nonadopted or adopted adolescents. CONCLUSIONS: Maternal depression was an environmental liability for lifetime diagnoses of major depression and disruptive disorders in adolescents. Paternal depression was not associated with an increased risk for psychopathology in adolescents.

Hicks, B.M., DiRago, A.C., Iacono, W.G., & McGue, M. (2009). Gene-environment interplay in internalizing disorders: Consistent findings across six environmental risk factors. Journal of Child Psychology and Psychiatry, 50(10), 1309-1317. PMCID: PMC2758614

  • Background: Behavior genetic methods can help to elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). To date, however, no study has conducted a comprehensive analysis examining multiple environmental risk factors with the purpose of delineating general mechanisms of G-E influence in the development of INT disorders. Methods: The sample consisted of 1315 male and female twin pairs participating in the age 17 assessment of the Minnesota Twin Family Study. Quantitative G-E interplay models were used to examine how genetic and environmental risk for INT disorders changes as a function of environmental context. Multiple measures and informants were employed to construct composite measures of INT disorders and six environmental risk factors including: stressful life events, mother-child and father-child relationship problems, antisocial and prosocial peer affiliation, and academic achievement and engagement. Results: Significant moderation effects were detected between each environmental risk factor and INT such that in the context of greater environmental adversity, nonshared environmental factors became more important in the etiology of INT symptoms. Conclusion: Our results are consistent with the interpretation that environmental stressors have a causative effect on the emergence of INT disorders. The consistency of our results suggests a general mechanism of environmental influence on INT disorders regardless of the specific form of environmental risk.

Niess, M.B., Stevenson, J., Legrand, L.N., Iacono, W.G., & Sedikides, C. (2009). Self-esteem, negative emotionality, and depression as a common temperamental core. Journal of Personality, 77(2), 327-346. PMCID: PMC2757924

  • We tested the structure and magnitude of genetic and environmental influences on the overlap among self-esteem, negative emotionality, and major depression symptoms in adolescent girls (N=706) from the Minnesota Twin Family Study. Genetic and environmental influences on all three operated via a general, heritable factor. Genetic influences explained the majority of overlap among the three constructs, as well as most of the variance in self-esteem and negative emotionality. Genetic influences on depression were more modest and largely due to genetic factors specific to depression. These findings support the theory that self-esteem, depression, and neuroticism represent aspects of a common temperamental core. The interrelations among the three constructs in mid-adolescence is consistent with their interrelations in adulthood.
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