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Accumulating research suggests a moderating role for the corticotropin-releasing hormone receptor 1 gene (CRHR1) in the association between childhood adversity and adult depression. The present study aims to replicate recent findings using different genetic variants and measures of early adversity assessed both prospectively and retrospectively. Data were collected in the context of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. 300 participants (137 males, 163 females) were genotyped for four CRHR1 SNPs (rs7209436, rs110402, rs242924, and rs17689882) and completed the Beck Depression Inventory at ages 19, 22 and 23 years. Childhood adversity was assessed using the Childhood Trauma Questionnaire and by a standardized parent interview yielding an index of family adversity. Our results indicate that CRHR1 and childhood adversity interacted to predict depressive symptoms in young adults. Specifically, we found that the impact of childhood maltreatment on adult depressive symptoms was significantly higher in individuals (i) with two copies of the CRHR1 TAT haplotype, and (ii) homozygous for the G allele of rs17689882. The interaction was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report, but not to prospectively ascertain objective family adversity. The present study partially replicates recent findings of a CRHR1 by childhood adversity interaction with regard to adult depression highlighting the subjective characteristics of the environmental pathogen that is operative in this interaction.
Recent evidence suggests that heterogeneity in the age at onset could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to examine interactions between two DAT1 polymorphisms and different initiation ages with regard to alcohol and tobacco consumption levels and dependence. Two hundred and ninety-one young adults (135 males, 156 females) participating in the Mannheim Study of Children at Risk were genotyped for the 40-bp variable number of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was assessed at age 15 and 19 years. Information about current alcohol and tobacco consumption was obtained at age 19 years using self-report measures and structured interviews. Results suggest that age at onset of intensive consumption moderated the association of the DAT1 gene with early adult substance use and dependence, revealing a DAT1 effect only among individuals homozygous for the 10r allele of the 40-bp VNTR who had started daily smoking or being intoxicated early in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting an early age at first intoxication showed higher current alcohol consumption at age 19 years. In contrast, no interaction between rs27072 and the age at first cigarette with regard to later smoking was observed. These findings provide evidence that the DAT1 gene interacts with an early heavy or regular drug exposure of the maturing adolescent brain to predict substance (ab)use in young adulthood. Further studies are required to confirm these findings.
Background: Dopamine plays an important role in orienting and the regulation of selective attention to relevant stimulus characteristics. Thus, we examined the influences of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of visual processing in a contingent negative variation (CNV) task.
Methods: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as preceding visual evoked potential components were assessed.
Results: Significant additive main effects of DAT1 and COMT on the occipito-temporal early CNV were observed. In addition, there was a trend towards an interaction between the two polymorphisms. Source analysis showed early CNV generators in the ventral visual stream and in frontal regions. There was a strong negative correlation between occipito-temporal visual post-processing and the frontal early CNV component. The early CNV time interval 500-1000 ms after the visual cue was specifically affected while the preceding visual perception stages were not influenced.
Conclusions: Late visual potentials allow the genomic imaging of dopamine inactivation effects on visual post-processing. The same specific time-interval has been found to be affected by DAT1 and COMT during motor post-processing but not motor preparation. We propose the hypothesis that similar dopaminergic mechanisms modulate working memory encoding in both the visual and motor and perhaps other systems.