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What Twin Studies of Adolescent Behavior Can Teach Us About Shared Environmental and Genetic Risk

      See Related Article p. 114
      During the 1990s, the prevalence of adolescent sexual intercourse in the United States declined, but the downward trend has since plateaued [
      • Martinez G.M.
      • Chandra A.
      • Abma J.C.
      • et al.
      Fertility, contraception, and fatherhood: Data on men and women from cycle 6 (2002) of the 2002 National Survey of Family Growth.
      ,
      • Martinez G.M.
      • Copen C.E.
      • Abma J.C.
      Teenagers in the United States: Sexual activity, contraceptive use, and childbearing, 2006-2010 national survey of family growth.
      ]. From 2002 onward, the typical age of first sexual intercourse has remained steady at about 17 years [
      • Martinez G.M.
      • Chandra A.
      • Abma J.C.
      • et al.
      Fertility, contraception, and fatherhood: Data on men and women from cycle 6 (2002) of the 2002 National Survey of Family Growth.
      ,

      Key statistics from the National Survey of Family Growth. National Center for Health Statistic. Available at: http://www.cdc.gov/nchs/nsfg/key_statistics/s.htm#vaginalsexual. Accessed October 1, 2013.

      ]. Risks stemming from early sexual debut are several-fold and notably include unplanned teen pregnancy, sexually transmitted diseases, and psychological strain. Adolescents engaging in sexual behavior before age 15 years are twice as likely to have a sexually transmitted disease by age 18 years and to report more sexual partners; they also are less likely to use any form of contraception and more likely to become pregnant before graduating high school relative to their later-onset peers [
      • Martinez G.M.
      • Copen C.E.
      • Abma J.C.
      Teenagers in the United States: Sexual activity, contraceptive use, and childbearing, 2006-2010 national survey of family growth.
      ,
      • Kaestle C.E.
      • Halpern C.T.
      • Miller W.C.
      • Ford C.A.
      Young age at first sexual intercourse and sexually transmitted infections in adolescents and young adults.
      ,
      • Wellings K.
      • Nanchahal K.
      • Macdowall W.
      • et al.
      Sexual behaviour in Britain: Early heterosexual experience.
      ]
      Because of these poorer health and social outcomes, adolescent medicine specialists have long been interested in identifying leading risk factors for early sexual debut, in the hopes of delivering more informed and targeted preventive interventions to those in greatest need. A significant body of research points to adolescent substance use as an early warning sign [
      • Zimmer-Gembeck M.J.
      • Helfand M.
      Ten years of longitudinal research on US adolescent sexual behavior: Developmental correlates of sexual intercourse, and the importance of age, gender and ethnic background.
      ]. In longitudinal studies, early-onset substance use (e.g., initiating tobacco and/or alcohol use before age 16 years) has been linked with earlier onset of sexual intercourse [
      • Zimmer-Gembeck M.J.
      • Helfand M.
      Ten years of longitudinal research on US adolescent sexual behavior: Developmental correlates of sexual intercourse, and the importance of age, gender and ethnic background.
      ]. This is important not only from a substance use education standpoint, but also with respect to sexual risk counseling. However, the mediating pathways of this finding taking into account shared cofactors (e.g., parenting, peers, individual differences) and sociodemographic (e.g., gender, race/ethnicity, income, sexual minority status) and other moderators complicate interpretations of simple cause–effect relationships [
      • Zimmer-Gembeck M.J.
      • Helfand M.
      Ten years of longitudinal research on US adolescent sexual behavior: Developmental correlates of sexual intercourse, and the importance of age, gender and ethnic background.
      ]. Although the temporal sequence of early substance use before sexual debut suggests a direct relationship, it is possible that both substance use and sexual debut are themselves governed by shared environmental and/or biological risks. A deeper understanding of these variables could help lead to a breakthrough in identifying new and better intervention targets and recognizing the antecedents of sexual health risks.
      Understanding the dynamics of the relationship between substance use and sexual debut has also been limited by research design and methods issues and statistical inferences. Sexual debut appears to follow the developmental principle of equifinality, with multiple competing and diverse processes experienced early in life that could lead to this same outcome. Moreover, the availability of well-matched controls is paramount to reduce random or extraneous information and isolate any early substance use effects in the data. One possible solution to this vexing challenge is a discordant twin study design. Discordant twin research allows one to elucidate causal relationships by controlling for both shared environmental and biological contexts [
      • McGue M.
      • Osler M.
      • Christensen K.
      Causal inference and observational research: The utility of twins.
      ]. In the case of monozygotic twins, a discordant twin set is a well-matched case-control pair that is identical in age, genetics, and, when reared together, shared life experiences [
      • McGue M.
      • Osler M.
      • Christensen K.
      Causal inference and observational research: The utility of twins.
      ]. As a result, one may more cleanly determine whether a non-shared exposure (e.g., early substance use onset) accounts for discordance on a given outcome (e.g., early sexual debut), and whether that relationship is attributable to shared environmental and/or biological factors.
      In this issue of the Journal of Adolescent Health, Deutsch and colleagues [
      • Deutsch A.R.
      • Slutske W.S.
      • Heath A.C.
      • et al.
      Substance use and sexual intercourse onsets in adolescence: A genetically informative discordant twin design.
      ] sought to extend the current literature by applying a twin design to inform new answers to old questions about the relationship between substance use and sexual intercourse onsets. Past twin design studies have reported that non-shared environmental factors are strongly influential, with 43% to 56% of the variance in alcohol use, smoking, and sexual intercourse onsets attributable to such effects [
      • Bricker J.B.
      • Stallings M.C.
      • Corley R.P.
      • et al.
      Genetic and environmental influences on age at sexual initiation in the Colorado Adoption Project.
      ,
      • Stallings M.C.
      • Hewitt J.K.
      • Beresford T.
      • et al.
      A twin study of drinking and smoking onset and latencies from first use to regular use.
      ]. Because non-shared environmental factors account for a large proportion of their variance, it is plausible that discordance in one factor (e.g., substance use onset) could lead to discordance in the other (e.g., sexual intercourse onset). When Deutsch and colleagues tested this relationship while controlling for symptoms of conduct disorder [
      • Deutsch A.R.
      • Slutske W.S.
      • Heath A.C.
      • et al.
      Substance use and sexual intercourse onsets in adolescence: A genetically informative discordant twin design.
      ], they learned that smoking and alcohol use onset were not predictive of sexual intercourse onset. Instead, the only significant predictor of sexual intercourse onset at both the within-twin and between-twin levels was onset of drunkenness, although this effect was modest.
      These results complicate the interpretation of prior longitudinal findings implicating substance use onset as a predictor of subsequent sexual intercourse [
      • Donahue K.L.
      • D'Onofrio B.M.
      • Lichtenstein P.
      • Langstrom N.
      Testing putative causal associations of risk factors for early intercourse in the study of twin adults: Genes and environment (STAGE).
      ]. It appears that underlying genetic and shared environmental factors can dually influence both of these outcomes. Interestingly, the results are consistent with another recent twin study demonstrating that early smoking and early cannabis use onset are not associated with early sexual intercourse [
      • Donahue K.L.
      • D'Onofrio B.M.
      • Lichtenstein P.
      • Langstrom N.
      Testing putative causal associations of risk factors for early intercourse in the study of twin adults: Genes and environment (STAGE).
      ]. Drawing from a large, Swedish population-based twin sample, adults reporting cigarette and cannabis use before 13 years of age were more likely to have sexual intercourse by age 16 years, but this relationship was predominantly attributed to both shared environmental and genetic factors [
      • Donahue K.L.
      • D'Onofrio B.M.
      • Lichtenstein P.
      • Langstrom N.
      Testing putative causal associations of risk factors for early intercourse in the study of twin adults: Genes and environment (STAGE).
      ].
      From a prevention standpoint, the data do not yet support the notion that delaying the onset of alcohol, tobacco, or cannabis use dramatically alters teens' sexual risk-taking behavior. Although educating adolescent patients about the dangers of alcohol and drug use is clearly important, in and of itself, this cannot substitute for delivering sexual risk counseling, too. A number of additional research questions also remain to be answered. First, the twin samples from Deutsch and colleagues [
      • Deutsch A.R.
      • Slutske W.S.
      • Heath A.C.
      • et al.
      Substance use and sexual intercourse onsets in adolescence: A genetically informative discordant twin design.
      ] (and Donahue and colleagues [
      • Donahue K.L.
      • D'Onofrio B.M.
      • Lichtenstein P.
      • Langstrom N.
      Testing putative causal associations of risk factors for early intercourse in the study of twin adults: Genes and environment (STAGE).
      ]) are primarily non-Hispanic white. Participants were also asked to recall the onset of risk behavior retrospectively. Whether these findings replicate in more racially and ethnically diverse samples, and assessing participants from early adolescence to adulthood, is unknown. Second, only sexual intercourse onset was reported. This outcome does not capture youth who engage in other sexual risk behaviors, such as oral sex. Finally, discordance between monozygotic twins does not ensure findings of causality. Other discordant non-shared environmental factors (e.g., individual differences in sensation seeking) may account for both substance use onset and sexual intercourse onset. Adolescent medicine practitioners and scientists must continue to strive toward understanding the factors that drive these adolescent risks, and determine meaningful intervention targets and strategies for this population.

      Acknowledgments

      The authors thank Anisha Abraham, MD, MPH, for comments on the manuscript.

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