Wilson, S., Hicks, B.M., Foster, K.T., McGue, M., & Iacono, W.G. (2015). Age of onset and course of major depressive disorder: Associations with psychosocial functioning outcomes in adulthood. Psychological Medicine, 45(3), 505-514. PMCID: PMC4289461

RESULTS: A recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood.
CONCLUSIONS: The negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

Wilson, S., DiRago, A.C., & Iacono, W.G. (2014). Prospective inter-relationships between late adolescent personality and major depressive disorder in early adulthood. Psychological Medicine, 44, 567-577. PMCID: PMC3795869

RESULTS: Multilevel modeling (MLM) analyses indicated that higher age-17 NEM was associated with the subsequent development of MDD, and any MDD, regardless of onset or course, was associated with higher NEM up to age 29. Moreover, the chronic/recurrent MDD groups failed to show the normative decrease in NEM from late adolescence to early adulthood. Lower age-17 PEM was also associated with the subsequent development of MDD but only among the chronic/recurrent MDD groups. Finally, the adolescent-onset MDD groups reported lower age-17 CON relative to the never-depressed and adult-onset MDD groups.
CONCLUSIONS: Taken together, the results speak to the role of personality traits for conferring risk for the onset of MDD in late adolescence and early adulthood, in addition to the pernicious implications of chronic/recurrent MDD, particularly when it onsets during adolescence, for adaptive personality development.

Wilson, S., Vaidyanathan, U., Miller, M.B., McGue, M., & Iacono, W.G. (2014). Premorbid risk factors for major depressive disorder: Are they associated with early onset and recurrent course? Development and Psychopathology, 26, 1477-1493. PMCID: PMC4244653

Abstract: Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age 11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual single nucleotide polymorphism based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset.

Marmorstein, N.R., Malone, S.M., & Iacono, W.G. (2004). Major depression and conduct disorder in youth: Associations with parental psychopathology and parent child-conflict. Journal of Child Psychology and 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.
(Am J Psychiatry 2004; 161:1588–1594)

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.

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.

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 30 UTRof 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%), P¼.001. 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 r2¼.030, F¼13.37, P¼.0003. By contrast, in men r2¼.00001, F¼0.002, P¼.96. These results are consistent with a gender-specific role of the CHRM2 gene in depression in women.
©2002 Wiley-Liss, Inc.