Adolescence and emerging adulthood represent an important developmental period during which substance use, misuse, and abuse occur concomitantly with important changes in neurocognitive development, mental health, and the social environment, with consequences for adult adjustment. Existing literature linking the effects of youth substance use to adult adjustment demonstrates the importance of these factors, but is largely correlational and cross-sectional, and leaves equivocal their causal role. Poor adult adjustment may be the result of youth substance misuse, including possible neurotoxic effects on brain development during this sensitive period. However, factors present prior to substance use initiation, such as genetic liability, pre- existing brain anomalies reflectng the manifestation of genetic risk, contextual risk, and comorbid disorders such as childhood disruptive disorders (CDDs), influence both adolescent substance exposure and adult outcomes. Existing research has typically not accounted for such factors. Thus, even the few longitudinal studies that exist are limited in the inferences they permit. We propose extending a prospective study of 453 twin pairs, first assessed at age 11, to determine young adult outcomes at age 24. To increase the likelihood that misuse of substances would be widespread and to ensure sufficient representation of high-risk females, half of our community-based twin sample was enriched for the presence of CDDs; the other half was selected at random and is thus representative of twins born in Minnesota. Study participants completed a day-long in- person intake assessment that included substance use, mental health, overall adjustment, environmental risk and protective factors, electrophysiological measurement, academic achievement, and cognitive ability. Participants were re-assessed at age 14, when many were initiating substance use, and again at age 17, when substance misuse was becoming apparent. Our sample's current value derives from the wealth of data already gathered on the timing, duration, frequency, and intensity of exposure to specific substances coupled with our careful assessments of the twins' behavioral, environmental, and familial characteristics throughout adolescence. We will capitalize on the value of this sample by undertaking a comprehensive assessment of age-24 outcomes that broadly covers substance use disorders, mental health (including persistence of CDDs), and psychosocial, electrophysiological, and neuropsychological outcomes. A subsample of 216 twin pairs will also undergo an MRI assessment, adding to the uniqueness of our study. Our data analytic strategy emphasizes the innovative application of a co-twin differences design, a powerful method for clarifying effects due to substance use from those due to unmeasured confounding factors, including genetic factors. This novel approach capitalizes on the differences in the history of substance misuse that occur naturally within twin pairs as they grow up, allowing us to separate the effects of substance abuse from familial and psychosocial risk factors that predate substance exposure on their overall adjustment and brain functioning as adults. 1

Public Health Relevance

This application examines the development of adult substance use disorder, mental health, psychosocial adjustment, and neurocognitive outcomes. Four hundred fifty-three twin pairs who have been prospectively assessed since age 11 will be examined to determine how twin discordance in substance use and abuse relates to twin differences in these outcomes at age 24. The project design allows for strong inferences to be made regarding the causal effects of adolescent and young adult substance use on age-24 adult adjustment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA036216-03
Application #
8826725
Study Section
Special Emphasis Panel (ZRG1-RPIA-N (09))
Program Officer
Gordon, Harold
Project Start
2013-07-01
Project End
2018-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
3
Fiscal Year
2015
Total Cost
$637,832
Indirect Cost
$218,205
Name
University of Minnesota Twin Cities
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Iacono, William G (2018) Endophenotypes in psychiatric disease: prospects and challenges. Genome Med 10:11
Harper, Jeremy; Malone, Stephen M; Iacono, William G (2018) Impact of alcohol use on EEG dynamics of response inhibition: a cotwin control analysis. Addict Biol 23:256-267
Korotana, Laurel M; von Ranson, Kristin M; Wilson, Sylia et al. (2018) Reciprocal Associations Between Eating Pathology and Parent-Daughter Relationships Across Adolescence: A Monozygotic Twin Differences Study. Front Psychol 9:914
Wilson, Sylia; Malone, Stephen M; Hunt, Ruskin H et al. (2018) Problematic alcohol use and hippocampal volume in a female sample: disentangling cause from consequence using a co-twin control study design. Psychol Med 48:1673-1684
Smit, Dirk J A; Wright, Margaret J; Meyers, Jacquelyn L et al. (2018) Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity. Hum Brain Mapp 39:4183-4195
Clark, Shaunna L; McClay, Joseph L; Adkins, Daniel E et al. (2017) Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence. Alcohol Clin Exp Res 41:711-718
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Sniekers, Suzanne; Stringer, Sven; Watanabe, Kyoko et al. (2017) Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nat Genet 49:1107-1112
Malone, Stephen M; McGue, Matt; Iacono, William G (2017) What can time-frequency and phase coherence measures tell us about the genetic basis of P3 amplitude? Int J Psychophysiol 115:40-56

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