# Adult Progression of Adolescent Onset Substance Use Disorder in a High Risk Sample

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $638,961

## Abstract

The research proposed in this application aims to understand risk and protective factors that promote
continuation and desistance of problematic substance use (SU) and antisocial behavior (ASB) that began in
adolescence. We propose a fourth wave of follow-up, approximately 18 years after initial recruitment, of an
extremely affected adolescent sample as they transition into middle adulthood; this is a developmental period
when we expect a portion of these individuals to decrease or desist problematic SU and associated high-risk
behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high
rates of morbidity and mortality. The aims of this proposal are to:
Aim 1: Identify risk factors that predict level and change (growth or decline) in SU and ASB from adolescence
to middle adulthood.
 a. We hypothesize that early age of onset, male sex, child maltreatment, neurocognitive deficits, and
 personality traits (behavioral undercontrol/impulsivity) will predict higher levels and more growth in SU
 and ASB.
 b. We hypothesize that genetic vulnerability as indexed by polygenic risks scores (PRS) will predict faster
 growth in SU and ASB that persists through later adulthood.
 c. We will explore mechanistic relationships; e.g., we hypothesize that the relationship between PRS and
 level and change of SU and ASB will be partially mediated by behavioral undercontrol/impulsivity.
Aim 2: Identify protective factors associated with level and change in SU and ASB.
 a. We hypothesize that adopting adult prosocial roles (education, employment, marriage, parenting) will
 be associated with lessened growth in SU and ASB.
 b. We hypothesize that treatment will be associated with greater desistance of SU and ASB than
incarceration.
 c. We will explore moderators of genetic vulnerability, specifically whether prosocial roles and treatment
 attenuate the effect of PRS on level of SU and ASB.
Aim 3: Determine the extent to which findings are specific to our highly selected sample of individuals with
early-onset SU and ASB or generalize more broadly by conducting comparative and joint analyses of data from
our high-risk sample with similar longitudinal data from our currently funded study of twins, an unselected
community-based sample.
 a. We hypothesize that risk and protective factors will operate similarly across the two samples, although
 we will have a greater magnitude of risk factors in the high-risk sample.
 b. We will confirm this hypothesis in joint analyses of the high-risk and community twin samples.

## Key facts

- **NIH application ID:** 10847494
- **Project number:** 5R01DA053693-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Christian J Hopfer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $638,961
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847494

## Citation

> US National Institutes of Health, RePORTER application 10847494, Adult Progression of Adolescent Onset Substance Use Disorder in a High Risk Sample (5R01DA053693-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10847494. Licensed CC0.

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