Abstract
Substance misuse and addictions impose serious health and socio-economic consequences for both individuals and societies. Substance use during adolescence predicts the severity of addictions in later life, indicating that adolescence is an important milestone for developing addictions. Alcohol and tobacco are the most common form of substance use in adolescents. The heritability estimates of alcohol and tobacco addictions range between 30 - 70%, suggesting that both genetic and environmental factors could contribute to the risks of addictions.This PhD thesis aimed to identify the genetic and epigenetic factors in alcohol and tobacco misuse in adolescence. The impact of life stress and circadian system on reward sensitivity and substance use was investigated in over 2000 adolescents from the IMAGEN Study. In the first study, both negative life events and ventral striatal activations during reward anticipation were shown to predict the increased alcohol and tobacco use in adolescents. The second study investigated the relationships among reward sensitivity, substance use and the DNA methylation in PERIOD 1, a circadian gene that was found to associate with stress-mediated alcohol use in adolescence (Dong et al., 2011). The third study explored the additive genetic and polygenic effects of single nucleotide polymorphisms (SNPs) in the stress and circadian systems on reward sensitivity and substance use. Results from the second and the third studies showed that reward sensitivity, alcohol and tobacco use in adolescents were not associated with the DNA methylation in PERIOD 1, and the genetic polymorphisms within the stress and circadian systems. The fourth study examined the genetic influence of stress systems on alcohol misuse. SNP rs1409837 on FYN oncogene related to SRC (FYN) gene was found to associate with the reduced drunkenness and binge drinking in adolescents at age 16. When investigating the role of FYN rs1409837 on brain functions, FYN rs1409837 was found to associate with the reduced amygdala activations during angry face processing. This thesis highlights the genetic influence of life stress on alcohol misuse and provides new approaches that should aid the understanding of genetic underpinnings of substance misuse in adolescence.
| Date of Award | 2014 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Sylvane Desrivieres (Supervisor), Jonathan Mill (Supervisor) & Gunter Schumann (Supervisor) |