Interactive Effects of the Serotonin Transporter 5-HTTLPR Polymorphism and Stressful Life Events on College Student Drinking and Drug Use

Background: The neuregulin 1 gene is a susceptibility gene for substance dependence. A functional polymorphism (SNP8NRG243177/rs6994992; C/T) in the promoter region of the brain-specific type IV neuregulin-1 gene ( NRG1) has been associated with psychiatric disorders (e.g. schizophrenia and bipolar disorder) that often present higher odds of smoking, alcohol and illicit drug use. This study assessed the association of the NRG1 genotype with drug use and possible interaction with stressful life events (SLEs). Methods: The database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998) was used. Cohorts of children initially 9 years old ( n=583; followed up at 15 and 18 years) and 15 years old ( n=593; followed up at 18 and 25 years) provided self-reports on alcohol, tobacco and illicit substance use and SLEs. Psychiatric assessment based on DSM-IV was carried out on the older birth cohort at age 25 to assess the lifetime presence of substance use disorders. NRG1 rs6994992 was genotyped in all participants by TaqMan® Pre-Designed SNP Genotyping Assay on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The minor (T) allele frequency was 0.37. Results: NRG1 rs6994992 C/C homozygotes, especially those who had experienced more SLEs, were more likely to develop alcohol use disorders by young adulthood, were generally more active consumers of tobacco products, and had more likely used illicit drugs. In T allele carriers, SLEs had a negligible effect on substance use. Conclusions: In humans, NRG1 genotype is associated with substance use, and this relationship is moderated by adverse life events, with a gain-of-function allele being protective.

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Stressful life events precede gambling problems, and continued gambling problems exacerbate stressful life events; a life course calendar study

10.31234/osf.io/t9x5a ◽

2021 ◽

Author(s):

Alex M T Russell ◽

Matthew Browne ◽

Nerilee Hing ◽

Tess Visintin ◽

Stephen Begg ◽

...

Keyword(s):

Drug Use ◽

Life Course ◽

Life Events ◽

Online Survey ◽

Stressful Life Events ◽

Adult Life ◽

Stressful Life ◽

Gambling Problems ◽

Memory Biases ◽

Loved One

Do stressful life events cause gambling problems, or do gambling problems cause stressful life events? This study used a retrospective design to examine the temporal order of these associations. Specifically, the study employed a life course calendar in a self-directed online survey to minimise memory biases common in retrospective designs. A total of 1,564 US respondents who had gambled at any point in their life (51.0% female, median age 46) were asked whether, for each year of their adult life, they had experienced each of eight stressful life events, and whether they had engaged in casual or heavy gambling, drinking or drug use, with heavy gambling defined in line with a problem gambling definition. We found that five stressful life events were associated with the onset of heavy gambling: work issues, financial issues, legal issues, relationship issues and the death of a loved one. The same five stressful life events predict the cessation of an episode of heavy gambling, indicating a possible tendency for gambling problems to self-resolve in the presence of stress. Insights are also gained into comorbidities with alcohol and drug use, and the course of stressful life events and gambling and substance use throughout the life course, albeit with a non-representative sample. The methodology allows tentative conclusions in terms of possible causation pathways, indicating that stressful life events may play a role both in the onset and the maintenance (or cessation) of gambling problems.

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