Adolescence is a critical period for the initiation and escalation of alcohol use and for the emergence of sex differences in alcohol use. The proposed research will test how changes in testosterone (T) during adolescence intersect with genetic influences on the development of alcohol use and related risk-taking behaviors. T levels increase dramatically from childhood through adolescence, particularly in males. Adolescent increases in T affect brain structure and function, including neural response to reward. Moreover, behavioral studies have found that individual differences in T predict alcohol use phenotypes, with stronger associations seen in boys than in girls. A largely independent stream of behavioral genetic research has established that genetic influences on substance use and related risk-taking behaviors increase over the course of adolescence. How these genetic influences intersect with hormonal changes during adolescence is unknown, as endocrine measures and behavioral genetic data have rarely been integrated. This gap is partly due to methodological challenges associated with measuring hormones in saliva: Single measures do not fully discriminate basal levels of hormones from state fluctuations (e.g., situational reactiviy, diurnal rhythm), while high-intensity repeated measurement is costly and burdensome to participants. The proposed research aims to overcome this barrier to research progress by using cutting-edge technology to measure accumulated T in hair. Hair T represents a 3-month hormonal accumulation and thus reflects chronic individual differences un- confounded with state fluctuations but sensitive to pubertal changes. We will examine the interplay between T and genetic influences on alcohol use in a sample of 500 twins (250 same-sex MZ and DZ pairs) ages 13-18. We will collect data on (1) T in saliva and hair, (2) reward sensitivity using a battery of in-lab behavioral tasks and self-report surveys, and (3) alcohol use using youth-report, parent-report, and school disciplinary records. This approach will address the following specific aims: (1) investigate the measurement of T in hair as a novel method that captures the underlying genetic signal better than salivary T, (2) examine T as an endophenotype that mediates genetic influences on alcohol use through its effects on reward sensitivity, and (3) examine T as a moderator of genetic influences on reward sensitivity and alcohol use (i.e., gene x hormone interaction). We hypothesize that accumulation of T in hair will represent a highly heritable endophenotype that both mediates and moderates genetic influences on alcohol use, with genetic risk being exacerbated in high T individuals. We also hypothesize that there will be sex differences in the gene > hormone > behavior links, with stronger associations evident in males than females, thus contributing to the emerging sex difference in alcohol use phenotypes. Given the novelty of measuring sex steroids in hair and the potential to illuminate genetic and epigenetic mechanisms underlying adolescent alcohol use, the project is both high-risk and high- reward, and is thus perfectly suited for the R21 mechanism.

Public Health Relevance

Adolescence is a critical period for the initiation and escalation of alcohol use and for the emergence of sex differences in alcohol use. Testosterone is a sex-linked hormone that increases during adolescence and influences brain structure and function. This project will examine interplay between genetic influences and hormonal influences on alcohol use. Results will inform efforts to identify youths at highest risk for early-onset alcool use disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA023322-02
Application #
8921929
Study Section
Neuroscience Review Subcommittee (AA)
Program Officer
Grandison, Lindsey
Project Start
2014-09-05
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Patterson, Megan W; Mann, Frank D; Grotzinger, Andrew D et al. (2018) Genetic and environmental influences on internalizing psychopathology across age and pubertal development. Dev Psychol 54:1928-1939
Grotzinger, Andrew D; Mann, Frank D; Patterson, Megan W et al. (2018) Twin models of environmental and genetic influences on pubertal development, salivary testosterone, and estradiol in adolescence. Clin Endocrinol (Oxf) 88:243-250
Grotzinger, Andrew D; Mann, Frank D; Patterson, Megan W et al. (2018) Hair and Salivary Testosterone, Hair Cortisol, and Externalizing Behaviors in Adolescents. Psychol Sci 29:688-699
Harden, K Paige; Mann, Frank D; Grotzinger, Andrew D et al. (2018) Developmental differences in reward sensitivity and sensation seeking in adolescence: Testing sex-specific associations with gonadal hormones and pubertal development. J Pers Soc Psychol 115:161-178
Grotzinger, Andrew D; Briley, Daniel A; Engelhardt, Laura E et al. (2018) Corrigendum to ""Genetic and environmental influences on pubertal hormones in human hair across development"" [Psychoneuroendocrinology 90 (2018) 76-84]. Psychoneuroendocrinology 98:253
Grotzinger, Andrew D; Briley, Daniel A; Engelhardt, Laura E et al. (2018) Genetic and environmental influences on pubertal hormones in human hair across development. Psychoneuroendocrinology 90:76-84
Tucker-Drob, E M; Grotzinger, A D; Briley, D A et al. (2017) Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair. Psychol Med :1-13
Patterson, Megan W; Cheung, Amanda K; Mann, Frank D et al. (2017) Multivariate analysis of genetic and environmental influences on parenting in adolescence. J Fam Psychol 31:532-541
Harden, K Paige; Kretsch, Natalie; Mann, Frank D et al. (2017) Beyond dual systems: A genetically-informed, latent factor model of behavioral and self-report measures related to adolescent risk-taking. Dev Cogn Neurosci 25:221-234
Silventoinen, Karri; Jelenkovic, Aline; Latvala, Antti et al. (2017) Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts. Twin Res Hum Genet 20:395-405

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