Interactions between the combined genotypes of 5-HTTLPR and BDNF Val66Met polymorphisms and parenting on adolescent depressive symptoms: A three-year longitudinal study.

BACKGROUND

The importance of multiple genes-environment interaction (G × E) has been highlighted in studies on depressive symptoms. 5-HTTLPR and BDNF Val66Met polymorphisms, with functional interconnection, have been implicated in the pathophysiology of depressive symptoms. However, little is understood about whether the interaction of 5-HTTLPR, BDNF Val66Met and parenting fits better with the epistatic or cumulative manner.

METHODS

865 adolescents (T1: M = 12.32, 50.2% girls) were included in a three-year interval longitudinal design. Standardized questionares about parenting and depressive symptoms were collected. Saliva samples were collected for genotyping.

RESULTS

Neither the concurrent nor longitudinal interaction of 5-HTTLPR, BDNF Val66Met and parenting (G × G × E) showed significant effects on depressive symptoms. The interaction between cumulative genotypes and positive parenting (CG × E) was significant, with the strong differential susceptibility model, for depressive symptoms concurrently but not longitudinally after statistical correction. Adolescents who carried 3 (i.e. SS and Val/Met, L allele and Val/Val) and 4 (i.e. SS and Val/Val), not 1 (i.e. L allele and Met/Met) or 2 cumulative susceptibility alleles (i.e. SS and Met/Met, L allele and Val/Met), reported fewer depressive symptoms if they had experienced higher levels of positive parenting, and more symptoms under lower levels of positive parenting.

LIMITATIONS

This study did not examine the 5-HTTLPR triallelic (rs25531) marker and did not include an external sample.

CONCLUSIONS

The combined effects of 5-HTTLPR and BDNF Val66Met polymorphisms functioned in a manner of cumulative rather than epistatic in response to positive parenting on early adolescent depressive symptoms.