2012 › Trails



Genetic studies: Genetically based reduced MAOA and COMT functioning is associated with the cortisol stress response - a replication study

Authors: Bouma EMC, Riese H, Doornbos B, Ormel J, Oldehinkel AJ

In 2007, Molecular Psychiatry published a unique study by Jabbi and colleagues, in which they showed that the combination of genetic variance in the MAOA and COMT gene was associated with increased responses of the HPA axis to stress. This finding was replicated in the TRAILS study and published as Letter to the Editor in Molecular Psychiatry. Our letter addresses the combined influence of the MAOA length polymorphism and the COMT val158met SNP on saliva cortisol responses towards a standardized social stress test in a large (n = 452) sample of adolescents (mean age 16.01 yrs, 38.5% girls, no oral contraceptive users). Jabbi et al. (1) showed that the COMT met/met genotype in combination with low MAOA, present in males predominantly, was associated with increased ACTH responses. We replicated this association in adolescent boys. The effect of COMT in the low MAOA group was different between boys and girls. The highest cortisol levels and most pronounced responses were observed in met/met boys while in val/val girls. This gender difference is in concordance with the hypothesized differential effects of high and low COMT functioning in the development of mental disorders in men and women. Our finding should be interpreted with caution; although our overall sample size was large, the low MAOA genotype group consisted of only 29 girls (relative to 100 boys).

Genetic studies: Effects of Divorce on Dutch Boys’ and Girls’ Externalizing Behavior in GXE Perspective: Diathesis Stress or Differential Susceptibility?

Authors: Nederhof E, Belsky J, Ormel J, Oldehinkel AJ

Effects of divorce on children’s behavioral development have proven to be quite varied across studies and most developmental and family scholars today appreciate the great heterogeneity in divorce effects. Thus, this inquiry sought to determine whether select dopaminergic genes previously associated with externalizing behavior and/or found to moderate diverse environmental effects (DRD2, DRD4, COMT) might moderate divorce effects on adolescent self-reported externalizing problems; and, if so, whether evidence of gene-environment (GXE) interaction would prove consistent with diathesis-stress or differential-susceptibility models of environmental action. Data from the first and third wave of the Dutch TRacking Adolescents’ Individual Lives Survey (TRAILS, n = 1,134) revealed some evidence of GXE interaction reflecting diathesis-stress but not differential susceptibility. Intriguingly, some evidence pointed to “vantage sensitivity”—benefits accruing to those with a specific genotype when their parents remained together, the exact opposite of diathesis-stress.

Genetic studies: Differential susceptibility in youth: evidence that 5-HTTLPR x positive parenting is associated with positive affect ‘for better and worse’

Authors: Hankin BL, Nederhof E, Oppenheimer CW, Jenness J, Young JF, Abela JRZ, Smolen A, et al.

Positive affect has been implicated in the phenomenological experience of various psychiatric disorders, vulnerability to develop psychopathology and overall socio-emotional functioning. However, developmental influences that may contribute to positive affect have been understudied. Here, we studied youths’ 5-HTTLPR genotype and rearing environment (degree of positive and supportive parenting) to investigate the differential susceptibility hypothesis that youth carrying short alleles of 5-HTTLPR would be more influenced and responsive to supportive and unsupportive parenting, and would exhibit higher and lower positive affect, respectively. Three independent studies tested this gene–environment interaction in children and adolescents (age range 9–15 years; total N=1874). In study 1 (N=307; 54% girls), positive/supportive parenting was assessed via parent report, in study 2 (N=197; 58% girls) via coded observations of parent–child interactions in the laboratory and in study 3 (N=1370;53% girls) via self report. Results from all the three studies showed that youth homozygous for the functional short allele of 5-HTTLPR were more responsive to parenting as environmental context in a ‘for better and worse’ manner. Specifically, the genetically susceptible youth (that is, S’S’ group) who experienced unsupportive, non-positive parenting exhibited low levels of positive affect, whereas higher levels of positive affect were reported by genetically susceptible youth under supportive and positive parenting conditions. These findings are consistent with the differential susceptibility hypothesis and may inform etiological models and interventions in developmental psychopathology focused on positive emotion, parenting and genetic susceptibility.