Association between the serotonin transporter triallelic genotype and eating problems is moderated by the experience of childhood trauma in women.

OBJECTIVE: This study investigated a potential interaction between the triallelic polymorphism of the serotonin transporter gene (SLC6A4) promoter and the experience of childhood trauma on the number of problem eating behaviors. METHOD: The study sample was comprised of 439 (64.7% female) Caucasian college students (mean age = 22.49, SD = 6.12). Participants completed questionnaires that assessed eating problems and experience of trauma in childhood (ages 0-12) and donated cheek cells for 5-HTTLPR and rs25531 genotyping. RESULTS: Women carrying a lower expressing allele (i.e., L(G) or S) who were exposed to higher levels of childhood trauma reported significantly higher mean numbers of eating problems (gender × genotype × trauma interaction, p = .006). DISCUSSION: These results are consistent with findings that the lower expressing alleles of the SLC6A4 promoter are associated with increased sensitivity to the negative impact of childhood stressors on adult behavioral outcomes.

Serotonin Transporter (5-HTTLPR) Genotype and Childhood Trauma are Associated with Individual Differences in Decision Making.

The factors that influence individual differences in decision making are not yet fully characterized, but convergent evidence is accumulating that implicates serotonin (5-HT) system function. Therefore, both genes and environments that influence serotonin function are good candidates for association with risky decision making. In the present study we examined associations between common polymorphisms in the serotonin transporter gene (SLC6A4; 5-HTTLPR and rs25531), the experience of childhood trauma and decision making on the Iowa gambling task (IGT) in 391 (64.5% female) healthy Caucasian adults. Homozygosity for the 5-HTTLPR L allele was associated with riskier decision making in the first block of 20 trials (i.e., decision making under ambiguity, p = 0.004). In addition, mean IGT performance was significantly worse in blocks 3-5 (i.e., decision making under risk, p ≤ 0.05) for those participants who reported experiencing higher levels of childhood trauma. Our findings add to the growing evidence that genetic variation in the 5-HT system is associated with individual differences in decision making under ambiguity; and we report that the experience of childhood trauma is associated with relatively poor decision making under risk.

Description and validation of a dynamical systems model of presynaptic serotonin function: genetic variation, brain activation and impulsivity.

Despite more than a decade of empirical work on the role of genetic polymorphisms in the serotonin system on behavior, the details across levels of analysis are not well understood. We describe a mathematical model of the genetic control of presynaptic serotonergic function that is based on control theory, implemented using systems of differential equations, and focused on better characterizing pathways from genes to behavior. We present the results of model validation tests that include the comparison of simulation outcomes with empirical data on genetic effects on brain response to affective stimuli and on impulsivity. Patterns of simulated neural firing were consistent with recent findings of additive effects of serotonin transporter and tryptophan hydroxylase-2 polymorphisms on brain activation. In addition, simulated levels of cerebral spinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) were negatively correlated with Barratt Impulsiveness Scale (Version 11) Total scores in college students (r = -.22, p = .002, N = 187), which is consistent with the well-established negative correlation between CSF 5-HIAA and impulsivity. The results of the validation tests suggest that the model captures important aspects of the genetic control of presynaptic serotonergic function and behavior via brain activation. The proposed model can be: (1) extended to include other system components, neurotransmitter systems, behaviors and environmental influences; (2) used to generate testable hypotheses.