The purpose of this study was to use longitudinal models to examine developmental shifts in the genetic and environmental influences underlying the emergence of NicD symptoms and MDD symptoms across the high-risk period of middle adolescence, when depressed mood and smoking initiation are emerging, to early adulthood, when point prevalence rates of both disorders have reached their peaks, and to examine the longitudinal associations between NicD and MDD symptoms after accounting for developmental continuity of these phenotypes. The findings support active, dynamic processes involving developmental changes in the magnitude of genetic and environmental influences on both NicD and MDD symptoms but no evidence supporting longitudinally predictive relationships between MDD and NicD symptoms after accounting for the stability and concurrent associations of these disorders.
As hypothesized, genetic influences on NicD and MDD symptoms increased between age 15 and age 18, a developmental period when independence and niche-fitting are likely to accelerate, but were relatively stable between ages 18 and 21. The rise in the influence of genetic factors demonstrated in this study likely occurred within the context of a cascade of interacting genes and environmental exposures that unfold over time and begin to emerge as symptoms of NicD and MDD during middle adolescence. Consistent with this idea, the present study findings also support the importance of environmental influences on MDD and NicD during this period, particularly environmental factors unique to individual twins rather than shared among family members. The increase in variance attributed to nonshared environmental influences may reflect key developmental tasks occurring during adolescence, such as growing independence, greater involvement with peers, and more time spent in extracurricular activities away from the family. Indeed, depression and nicotine use during adolescence have been associated with many such social risk factors, for example affiliation with peers who smoke and engage in deviant behavior (Hu, et al., 2006
), peer rejection and victimization (Prinstein, Cheah, & Guyer, 2005
), and peer relationships characterized by conflict and lack of trust (Eberhart & Hammen, 2006
). These cascades of interacting genetic and environmental influences on NicD and MDD occur within the context of other developmentally relevant domains of functioning (e.g., academic achievements, career successes and failures, interpersonal relationship problems), which may also influence the developmental course of NicD and MDD. Future research may investigate these moderating influences, for instance by testing hypotheses about larger genetic effects or stronger age-related increases in genetic influences for individuals who have high levels of affiliation with deviant peers, have experienced romantic relationship break-ups, or fail to complete schooling and/or obtain employment.
For both NicD and MDD, genetic influences on symptoms overlapped considerably across the three ages, suggesting that genetic factors are a significant part of the processes underlying the continuity of symptoms across development. Nonshared environmental factors, on the other hand, were almost entirely age-specific and thus contributed little to the stability of NicD and MDD symptoms across time. Instead, different nonshared environmental factors influenced MDD and NicD symptoms at different points in development. Changes in environmental risk factors are consistent with the major developmental transitions that occur during this period. For example, conflict with parents is an important predictor of psychopathology and substance use during adolescence (McGue, Elkins, Walden, & Iacono, 2005
) but is not likely to be as influental after young adults have moved out of their parents' homes.
The small shared environmental variance for both MDD and NicD across all three ages was somewhat surprising and may help explain inconsistencies in estimates of shared environmental influences across previous twin studies. Consistent with our summary of existing twin research on depression and smoking in samples of youth, at younger ages shared environmental influences accounted for a larger proportion of variance in symptoms than genetic influences for both phenotypes (but especially for NicD), and at older ages the reverse was true for both disorders. In fact, the proportions of variability accounted for by shared environmental influences diminished with age to nearly zero by early adulthood. It is important to note, though, that the decline in the relative proportion of shared environmental influence compared to genetic and nonshared environmental influences is almost entirely a reflection of the rather dramatic increase in both genetic and nonshared environmental variance during this period, rather than the slight (and nonsignificant) decline in shared environmental variance.
Since symptoms of NicD were more heritable than symptoms of MDD and environmental factors shared among family members (though minimally influential overall) were more important for NicD than MDD, it follows that environmental influences unique to each twin were more important sources of variability in MDD symptoms than NicD symptoms. In fact, 66–88% of the variability in MDD symptoms could be attributed to these influences. Characteristics of the family environment, such as family stress (Fendrich, Warner, & Weissman, 1990
), parent-child conflict (Shiner & Marmorstein, 1998
), and interparental conflict (Fergusson, Horwood, & Lynskey, 1995
) have consistently been found to be important correlates of elevated risk for depression in adolescents. Integrating this research with our findings suggests that the role of these family factors in the development of depression is via individual processes not shared among family members (i.e., diverse experiences and responses to family stress and conflict for different family members), an idea consistent with developmental psychopathology principles that emphasize individual trajectories of risk (Rutter & Sroufe, 2000
) and the tendency for individuals to experience and perceive family characteristics in different ways (Rutter, 1999
Finally, as expected, there was considerable developmental continuity of MDD and NicD symptoms across adolescence and into early adulthood. Within disorder stability was stronger for NicD than MDD, which may be related to the episodic nature of depression and to stronger genetic influences on NicD symptoms than MDD symptoms, since genetic effects were shown to contribute to stability of symptoms over time. Consistent with research supporting the co-occurrence of smoking and depressed mood in adolescents and young adults (Fergusson et al., 1996
), NicD symptoms were associated concurrently with MDD symptoms at all three ages, and diagnoses of MDD were more common among individuals with NicD and vice versa. These associations were relatively small in magnitude, which is not unexpected given variability in effect sizes for associations between smoking and depression in the literature and the paucity of comparable research employing interviews to measure clinically-relevant constructs in adolescents and young adults. Although we identified small, significant associations between symptoms of the disorders across ages, after accounting for stability within disorders over time, associations between symptoms of one disorder at an earlier point in time did not predict symptoms of the other disorder at a later point in time. The cross-lagged model, though, supported correlated age-specific sources of variance for NicD and MDD symptoms at age 18, indicating that the two disorders have correlated risk factors and perhaps share common nonshared environmental risk factors, possibly risks related to peer affiliation and relationships. Since most previous studies did not adequately account for stability within disorders across time or use clinically-relevant measures, these findings provide important new information about the longitudinal relationships between MDD and NicD.
Strengths and Limitations
A few study limitations should be noted. First, the measures of depression and nicotine use selected for this study had clinical relevance but were limited in their developmental sensitivity to the emergence of problems and ability to detect variability in symptoms at age 15, perhaps contributing to the small magnitude MZ twin correlations evident at age 15. Use of more developmentally sensitive measures (e.g., initiation of smoking, less severe depressed mood) may provide more variability, reliability of estimates, and the ability to examine genetic and environmental effects at younger ages. However, our study had the advantage of assessing the same clinically relevant measures of DSM criteria across all three assessments, and the low rates of symptom endorsement at age 15 are descriptive of individuals at this age in this general population sample.
Second, while an important strength of the clinical interviews was their ability to assess symptoms during the entire period between time points, the three-year intervals may have been too long to detect the predictive effects of one of these disorders on the other. For instance, MDD may predict NicD when NicD is measured immediately following a depressive episode, with this effect weakening over longer durations of time. Future research that studies the longitudinal relationship between these constructs across the same high-risk developmental period but at shorter intervals may pinpoint a more precise timeline (especially between ages 15 and 18) when the developmental shifts in genetic and environmental effects occur.
Third, biometric modeling partitions variance into additive genetic, shared environmental, and nonshared environmental effects but does not provide information about specific genes, environmental risks, or targets for interventions and does not inform about causal processes (Rutter & Sroufe, 2000
). The Cholesky decomposition models used in this study do not separate or identify gene-environment or epistatic genetic effects. Research on the interplay of specific genes and environmental risk factors across this developmental period will be important for specifying the nature of changing etiological factors.
Finally, the participants were primarily Caucasian, which reflects the community from which the twins were selected but limits generalizability of the findings to other groups. In addition, since the participants in the study were twins, the findings may not be applicable to singletons. However, various lines of research support the applicability of findings from samples of twins, such as studies finding few differences in rates of psychopathology between twins and singletons (e.g., Kendler, Martin, Heath, and Eaves, 1995).
This study also has several methodological strengths. First, the age range of participants was broad (approximately 15 years to 21 years), but participants were assessed at discrete ages (i.e., variability in age at each assessment was low), which provided the opportunity to study change across the high-risk period while also examining effects at important, distinct points during development. Second, the sample had low attrition across assessments and was a representative community sample, which makes it possible to generalize findings to non-clinical populations. Third, clinical interviews were used to assess symptoms throughout the entire period from age 15 to 21, which provides clinically relevant measures and fills gaps in behavior genetics research on depression and nicotine use in youth samples, which have almost exclusively relied on self-report measures of current problems. These strengths, especially the longitudinal design, clinical measures, discrete ages at assessments, and models that account for limitations in the previous research (e.g., stability of disorders), allowed us to address unanswered questions about age-related changes in the genetic and environmental influences on depression and nicotine dependence and longitudinal associations between depression and nicotine dependence during the critical years of adolescence and early adulthood.
In summary, genetic and environmental factors were involved in the developmental cascade of risks explaining the rise in symptoms of NicD and MDD between age 15, when levels of symptoms were low and individual variability in symptoms were small, and late adolescence/early adulthood, when symptoms were at peak levels and individual variability was more substantial. This high risk period, especially between ages 15 and 18 years, is a critical time for changes in etiological factors as genetic influences become more important, new genetic influences emerge, and nonshared environmental influences contribute to greater variability in susceptibility to depression and nicotine dependence. Individuals high in symptoms of one disorder were likely to be high in symptoms of the same disorder later in development. This developmental continuity was largely explained by genetic factors. Environmental factors uniquely experienced by one twin and not the other were influential in the development of both disorders, but especially depression. These environmental factors were developmentally-specific and tended to explain variability at only one age. MDD and NicD symptoms co-occurred at the same time, had small associations across ages, and had correlated age-specific risk factors at age 18. However, after accounting for the stability of the two disorders, there were no cumulative cascade effects from one disorder to the other over the assessed time intervals, calling into question the causal role of one disorder in the developmental cascade of the other disorder.
Understanding developmental changes in genetic and environmental factors has implications for intervening and treating NicD and MDD. Given the large overlap in genetic influences across the three discrete ages, early interventions that target children with high genetic-risk (e.g., a parent with the disorder) may yield “high returns” (Heckman, 2006
) and thus may help reduce the economic and health burdens associated with these disorders. Furthermore, identifying intergenerational cascades of effects that link risk in one generation with risk in the next generation has practical implications for pinpointing and targeting specific predictors of risk and “buffers” that promote resilience (Serbin & Karp, 2004
). For example, interventions for children of depressed parents may target building resilience to genetic risks, such as developing skills to minimize the effects of their own genetically-influenced proneness to negative affectivity, and protecting against environmental mechanisms of intergenerational transmission of risk, such as learning to cope with the fluctuating moods and parenting practices of their depressed parent. The development of effective resilience skills may ultimately reduce negative chain reactions (Rutter, 1999
) and help prevent problems across development. At the same time, given evidence of age-specific genetic and environmental risk factors, preventative interventions must be ongoing, take into account individual family members' unique experiences of family risk factors, adjust to individuals' developmental levels, and consider age-specific risk factors.