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Developmental Pathways from Genetic, Prenatal, Parenting and Emotional/Behavioral Risk to Cortisol Reactivity and Adolescent Substance Use: A TRAILS Study.

ABSTRACT: Cortisol reactivity is a frequently studied biomarker of substance use, though infrequently examined in adolescence. However, past research provides evidence that multiple developmental influences, including genetics and both prenatal and postnatal environmental influences, contribute both to cortisol reactivity and adolescent substance use. The aim of this study was to assess the impact of these earlier developmental influences on cortisol reactivity to a social stress challenge and adolescent substance use (smoking, alcohol, and marijuana use frequency assessed at age 16 years), using data from the TRacking Adolescents' Individual Lives Survey (TRAILS; N=?2230 adolescents, 51% female). Developmental pathways included polygenic risk, prenatal stress, warm parenting (age 11), and internalizing and externalizing problems (intercepts and change from 11-16 years). Cortisol reactivity was associated with smoking but not alcohol or marijuana use. Externalizing problems were the stronger predictor of adolescent substance use, but internalizing problems also had an important role. Prenatal stress and middle childhood parenting operated via middle childhood externalizing problems, and parenting also operated via trajectories of growth of externalizing problems in predicting adolescent substance use outcomes. Further, there were protective effects of internalizing problems for alcohol and marijuana use in the context of a more comprehensive model. These developmental influences did not attenuate the association of cortisol reactivity and smoking. These findings suggest a need to understand the broader developmental context regarding the impact of internalizing pathways to substance use, and that it is unlikely that cortisol reactivity and smoking are associated solely because of common developmental influences.

SUBMITTER: Marceau K

PROVIDER: S-EPMC6998145 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Developmental Pathways from Genetic, Prenatal, Parenting and Emotional/Behavioral Risk to Cortisol Reactivity and Adolescent Substance Use: A TRAILS Study.

Marceau Kristine K Brick Leslie A LA Knopik Valerie S VS Reijneveld S A SA

Journal of youth and adolescence 20191130 1

Cortisol reactivity is a frequently studied biomarker of substance use, though infrequently examined in adolescence. However, past research provides evidence that multiple developmental influences, including genetics and both prenatal and postnatal environmental influences, contribute both to cortisol reactivity and adolescent substance use. The aim of this study was to assess the impact of these earlier developmental influences on cortisol reactivity to a social stress challenge and adolescent ...[more]

PMID: 31786769

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Project description:Innate differences in human temperament strongly influence how individuals cope with stress and predispose for specific types of psychopathology. The present study examines the developing brain in an animal model of temperamental differences to understand how altered neurodevelopment may engender differences in emotional reactivity that are stable throughout the animal’s life. We utilize selectively-bred High Responder (bHR) and Low Responder (bLR) rats that exhibit dramatic emotional behavior differences, with bHRs exhibiting exaggerated novelty-exploration, aggression, impulsivity and drug self-administration, and bLRs showing marked behavioral inhibition, exaggerated anxiety- and depressive-like behavior. Using Affymetrix microarrays, we assessed bLR/bHR gene expression in the developing brain on postnatal days (P)7, 14, and 21, focusing on the hippocampus and nucleus accumbens, two regions related to emotionality and known to differ in adult bLR/bHR rats. We found dramatic bLR/bHR gene expression differences in the P7 and P14 hippocampus, with minimal differences in the nucleus accumbens. Some of the most profound differences involved genes critical for neurodevelopment and synaptogenesis. Stereological studies evaluated hippocampal structure in developing bHR/bLR pups, revealing enhanced hippocampal volume and cell proliferation in bLR animals. Finally, behavioral studies showed that the bHR/bLR behavioral phenotypes emerge very early in life, with exploratory differences apparent at P16 and anxiety differences present by P25. Together these data point to specific brain regions and critical periods when the bHR/bLR phenotypes begin to diverge, which may eventually allow us to test possible therapeutic interventions to normalize extreme phenotypes (e.g. the anxiety-prone nature of bLRs or drug addiction proclivity of bHRs). 2x2x3 factorial design with N=6 per group. Factors as follows: 1) Two selectively bred strains of rats (derived from an original Sprague Dawley population) termed High Responders (HR) and Low Responders (LR), 2) Two brain regions, Hippocampus (HPC) and Nucleus Accumbens (N.Acc), 3) Three developmental timepoints, specifically postnatal days 7 (P7), 14 (P14) and 21 (P21).

Dataset Information

Developmental Pathways from Genetic, Prenatal, Parenting and Emotional/Behavioral Risk to Cortisol Reactivity and Adolescent Substance Use: A TRAILS Study.

Publications

Developmental Pathways from Genetic, Prenatal, Parenting and Emotional/Behavioral Risk to Cortisol Reactivity and Adolescent Substance Use: A TRAILS Study.

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