Previously, sequence variation in the glucocorticoid (GR) and mineralocorticoid (MR) receptor genes (NR3C1 and NR3C2, respectively) have been found to be associated with physiological stress responses to social stress tests in small samples of adult men and oral contraceptives (OC) using women. Associations between single nucleotide polymorphisms (SNPs) in the GR (23EK-rs6190, 9beta-rs6198, BclI - rs4142324) and the MR gene (I180V-rs5522 and -2G/C (rs2070951) with cortisol and heart rate responses to a performance-related social stress task (public speaking and mental arithmetic) were examined in a large sample (n = 553) of adolescents (15-17 yrs). To make comparisons with previous findings, associations were tested in boys (n = 277, free-cycling (FC) girls (n = 183) and OC users (n = 94). None of the previously reported associations in adults could be replicated in this large adolescent sample. Explanations for non-replication are discussed.
Aims The aims of the present study were to determine the direct effect of DRD2 and DRD4, as well as their interaction with parenting (i.e. rejection, overprotection and emotional warmth), on the development of regular alcohol and cannabis use in 1192 Dutch adolescents from the general population.
Methods Information was obtained by self-report questionnaires. Perceived rejection, overprotection and emotional warmth were assessed at age 10-12. Regular alcohol and cannabis use were determined at age 15-18 and defined as the consumption of alcohol on 10 or more occasions in the past four weeks, and the use of cannabis on 4 or more occasions in the past four weeks. Models were adjusted for age, sex, parental alcohol or cannabis use, and externalizing behavior.
Results Carrying the A1 allele of the DRD2 TaqIA polymorphism, or the 7 repeat DRD4, was not directly related to regular alcohol or cannabis use. In addition, adolescent carriers of these genetic risk markers were not more susceptible to the influence of less optimal parenting. Main effects for parenting indicated that overprotection increased the risk of regular alcohol use, whereas the risk of cannabis use was enhanced by parental rejection and buffered by emotional warmth.
Conclusions Our findings do not support an association between DRD2/DRD4 and regular alcohol and cannabis use in adolescents. Given the substance-specific influences of rejection, overprotection and emotional warmth, these parenting factors might be promising candidates for prevention work.
The purpose of the present study was to investigate whether a length polymorphism in the dopamine receptor D4 gene (DRD4) was associated with approach related traits in adolescents. Data were used from TRAILS (TRacking Adolescents’ Individual Lives Survey), a population based cohort of Dutch adolescents. Sensation seeking, assessed with personality questionnaires from the participants themselves and their biological father and mother (n = 1282) was not associated with DRD4 genotype. Gambling performance (n = 591) and startle reactivity (n = 432) were not associated with DRD4 genotype either. Explanations for the dissociation might be sought in differences in development of the limbic system and the prefrontal cortex, both with high dopamine receptor D4 densities and both involved in approach related behaviours.
Psychologists, with their long-standing tradition of studying mechanistic processes, can make important contributions to further characterizing the risk associated with genes identified as influencing risk for psychiatric disorders. We report one such effort with respect to CHRM2, which codes for the cholinergic muscarinic 2 receptor and was of interest originally for its association with alcohol dependence. We tested for association between CHRM2 and prospectively measured externalizing behavior in a longitudinal, community-based sample of adolescents, as well as for moderation of this association by parental monitoring. We found evidence for an interaction in which the association between the genotype and externalizing behaviour was stronger in environments with lower parental monitoring. There was also suggestion of a crossover effect, in which the genotype associated with the highest levels of externalizing behavior under low parental monitoring had the lowest levels of externalizing behavior at the extreme high end of parental monitoring. The difficulties involved in distinguishing mechanisms of gene-environment interaction are discussed.