TY  - JOUR
A1  - Laucht, Manfred
A1  - Becker, Katja
A1  - Frank, Josef
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Treutlein, Jens
A1  - Skowronek, Markus H.
A1  - Schumann, Gunter
T1  - Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence
N2  - Objective: To clarify the nature of the association between dopamine genes and smoking by examining whether genetic variability in components of the dopamine pathway could explain refined phenotypes in adolescent smoking progression. Method: Data are from an ongoing prospective study of the long-term outcome of early risk factors studied since birth. At age 15 years, 220 participants (108 males, 112 females) completed a self-report questionnaire measuring smoking behavior and were genotyped for five dopamine gene variants. Results: Smoking initiation was related to allelic variation in the dopamine D-4 receptor gene (DRD4), whereas smoking continuation and dependence showed association with the dopamine D-2 receptor gene (DRD2). Adolescents with the seven-repeat allele of the common DRD4 exon 3 polymorphism had rates of ever smoking that were significantly higher than in those with other genotypes. Once smoking started, carriers of the T allele of a single nucleotide polymorphism of DRD2 (rs4648317) reported higher rates of current smoking and scored higher on nicotine dependence than their allelic counterparts. Among current smokers, intention to quit was significantly lower in adolescents homozygous for the 10-repeat allele of the common dopamine transporter 3 untranslated region polymorphism. Conclusions: Our results provide preliminary evidence of genetic influences on different stages of smoking and suggest the importance of specific dopamine genes in smoking progression in adolescence.
Y1  - 2008
U6  - https://doi.org/10.1097/Chi.0b013e31816bff77
SN  - 0890-8567
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Skowronek, Markus H.
A1  - Becker, Katja
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Rietschel, Marcella
A1  - Schulze, Thomas G.
T1  - Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/ hyperactivity disorder symptoms among 15-year-olds from high-risk community sample
N2  - Context: Recent evidence suggests that gene X environment interactions could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with attention-deficit/hyperactivity disorder (ADHD). 1bjective: To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in. adolescents from a high-risk community sample. Design: Prospective cohort study. Setting: Data were taken from the Mannheim Study of Children at Risk, an ongoing longitudinal study of the long-term outcomes of early risk factors followed up from birth on. Participants: Three hundred five adolescents (146 boys, 159 girls) participated in a follow-up assessment at age 15 years. Main Outcome Measures: Measures of ADHD symptoms according to DSM-IV were obtained using standardized structural interviews with adolescents and their parents. Psychosocial adversity was determined according to an "enriched" family adversity index as proposed by Rutter and Quinton. DNA was genotyped for the common DAT1 40-base pair (bp) variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region; 3 previously described single nucleotide polymorphisms in exon 15, intron 9, and exon 9; and a novel 30-bp VNTR polymorphism in intron 8. Results: Adolescents homozygous for the 10-repeat allele of the 40-bp VNTR polymorphism who grew up in greater psychosocial adversity exhibited significantly more inattention and hyperactivity-impulsivity than adolescents with other genotypes or who lived in less adverse family conditions (significant interaction, P=.013-017). This gene X environment interaction was also observed in individuals homozygous for the 6-repeat allele of the 30-bp VNTR polymorphism and the haplotype comprising both markers. Conclusions: These findings provide initial evidence that environmental risks as described by the Rutter Family Adversity Index moderate the impact of the DAT1 gene on ADHD symptoms, suggesting a DAT1 effect only in those individuals exposed to psychosocial adversity.
Y1  - 2007
UR  - http://archpsyc.ama-assn.org/
SN  - 0003-990X
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Skowronek, Markus H.
A1  - Becker, Katja
A1  - Schulze, Thomas G.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Rietschel, Marcella
T1  - Environmental risk factors and attention-deficit : hyperactivity discorder symptoms ; reply
Y1  - 2008
SN  - 0003-990X
ER  -