Susceptibility genes, social environmental risk factors and their interactions in internalizing disorders among...

Analyses of large scale psychiatric epidemiology surveys suggest that common mental disorders can be generalized into two underlying dimensions, internalizing disorders (e.g. depression, and anxiety) and externalizing disorders (e.g. addictions). The present study explores the interactions among the genes (SLC6A4, BDNF, and MAOA) and selected environment factors (G×E), and gene×gene (G×G) interactions for internalizing disorders in the sample of Chinese university students.

This is a genetic case control study. 259 undergraduates affected with internalizing disorders and 269 healthy controls were included. Multiple logistic regression was used to explore the potential environmental risk factors. G×E interactions were analyzed using the method developed by Mukherjee et al. (2008). Analyses of G×G interactions were conducted by generalized multifactor dimensionality reduction (GMDR) (Lou et al., 2007). We have previously reported on the polymorphism information for ten single nucleotide polymorphisms (SNPs) on SLC6A4, BDNF, and MAOA genes (Meng et al., 2009; Meng, 2010).

We found that an offspring's reported parents' negative mood, subject's unwillingness to express emotion, being an only child, having an unfulfilling relationship with his/her mother, and increased activity and behavior restrictions by his/her father were social environment risk factors for internalizing disorders. No statistically significant interactions were found in the G×E analyses. G×G analyses found that subjects with mutational alleles concurrently on rs10835210 and rs2030324 (BDNF gene) were significantly likely to develop internalizing disorders. Those with one mutated allele on either SNPs were 1.761 times, and those with both mutated alleles were 3.353 times, more likely to develop internalizing disorders.

A negative family emotional environment was found to be associated with internalizing disorders. BDNF gene variants were also found to be similarly associated. Using conservative statistical analyses we did not find any G×E interactions.