Childhood Maltreatment and County-Level Deprivation Jointly Modify the Effect of Serotonin Transporter Promoter Genotype on Depressive Symptoms in Adolescent Girls

Abstract

Depression is a commonly occurring mood disorder defined by the presence of persistent sad feelings, low energy, loss of interest in activities that were once pleasurable, feelings of guilt or low self-worth, disturbed sleep or appetite, and poor concentration, among other symptoms (American Psychiatric Association, 1994). Among adults 18 and older in the United States, the prevalence of major depressive disorder (MDD) is higher than that of any other commonly occurring DSM-IV mental disorder in the U.S., with a lifetime prevalence of 16.6%, and 12-month prevalence estimated at 6.7% (Kessler & Wang, 2008). The World Health Organization estimates that depression will rank second among the leading contributors of disease burden by the year 2020 (WHO, 2009). MDD is associated with enormous costs to both the individual and society, with the economic burden of depression estimated to be $83 billion per year as of 2000 (Greenberg et al., 2003), and the impairment in proper role functioning due to MDD known to be significantly worse when compared to a number of commonly occurring chronic medical disorders (Druss et al., 2009). The large public health burden of MDD is due, at least in part, to its onset relatively early in life: at least 25% of lifetime MDD cases start before age 19 (Kessler et al., 2005). Despite substantial research, our understanding of the factors that contribute to the etiology of depression remain incomplete. Genetic factors account for an estimated 35-45 percent of the variance in risk for depressive symptoms (Shih et al., 2004). In addition, meta-analysis supports an association between polymorphisms in six different candidate genes and MDD (Lopez-Leon et al., 2008). Nevertheless, there is growing recognition that genetic influences on depression may only be evident under certain environmental conditions—i.e. that there may be gene X environment (G X E) interactions, such that individuals of the same genotype may express different phenotypes depending on their environmental contexts (Moffitt et al., 2005). In particular, a growing body of work indicates that genetic variation, in combination with adverse experiences early in life, shape risk for mental illness.