Maternal depressive history, teen 5HTTLPR genotype, and the processing of emotional faces: Exploring mechanisms of risk

Abstract

Variations in the serotonin transporter gene (5HTTLPR) and biased processing of face-emotion displays both have been implicated in the transmission of depression risk, but little is known about developmental influences on these relationships. Within a community sample of adolescents, we examine whether 5HTTLPR genotype moderates the link between maternal depressive history and errors in face-emotion labeling. When controlling for current levels of depression and anxiety among youth, a two-way interaction between maternal depressive history and 5HTTLPR genotype was detected. Specifically, adolescents whose mothers reported a depressive history and who had a low expressing genotype made more errors in classifying emotional faces when compared with adolescents with an intermediate or high expressing genotype, with or without maternal depression history. These findings highlight the complex manner in which maternal depression and genetic risk may interact to predict individual differences in social information processing.

Introduction

Children of parents with depression face increased risk for depression themselves (Sullivan, Neale, & Kendler, 2000), particularly during adolescence (Williamson, Birmaher, Axelson, Ryan, & Dahl, 2004). Various potential mechanisms for this increased risk have been explored, including the contribution of genetics (Gross & Hen, 2004) and, more recently, biases in the processing of emotion (Gibb, Benas, Grassia, & McGeary, 2009).

Factors that affect the brain circuits implicated in major depressive disorder (MDD) also affect face-emotion identification (Drevets, 2003). Specifically, the serotonergic system influences neural processing of emotion, presumably through effects on amygdala-based circuitry (Harii et al., 2002). Variation in 5HTT function has been linked to accuracy in identifying faces (Marsh et al., 2006), as well as both perturbed amygdala-ventrolateral prefrontal cortex (vPFC) function (Hariri et al., 2002) and risk for MDD (Gross & Hen, 2004). Specifically, lesions in the amygdala or the ventral prefrontal cortex (vPFC), two key brain structures implicated in MDD, disrupt face-emotion identification proficiency. Collectively, evidence suggests that the brain circuitry implicated in MDD is also involved in face-emotion identification proficiency (e.g., Adolphs, 2002, Rolls, 2008). This suggests that research on face-emotion identification informs understanding of MDD pathophysiology.

However, key questions in this area remain. First, inconsistencies in research linking risk for MDD to the processing of emotional faces may reflect interaction with genetic risk (e.g., Lau et al., 2009). While not without controversy (Risch et al., 2009), some evidence suggests that the 5HTT low expressing allele moderates the association between life stress and depressive symptomatology (Caspi et al., 2003). Similar moderating influences might occur for the relationship between MDD and face-emotion processing; however, the role of these complex pathways in MDD risk remains imprecisely mapped. Prior work suggests that perturbations in the 5HT system early in development may relate both to later life risk for MDD and difficulties processing facial emotions, possibly through effects on a core underlying neural architecture. For example, Monk et al. (2008) found that children of parents with MDD, much like depressed adults and carriers of the 5HTTLPR low expressing allele, exhibit abnormal amygdala response to fearful faces. However, because this investigation did not examine the impact of 5HTTLPR on face processing and its association with familial risk, the role of serotonin remains unclear. Elucidation of the pathophysiology of MDD may derive from studies examining face processing in relation to genotype and development.

The goal of this report is to advance understanding of the relationship between risk for MDD and identification of emotional facial expressions in youth. We hypothesize that deficits in the processing of emotional faces may reflect broader deficits in emotion regulation. However, few studies examine facial processing deficits among youth at familial risk for depression, and these studies report inconsistent findings (Gibb et al., 2009, Joorman et al., 2007). The current investigation focuses specifically on face-emotion identification, a particularly important process that has been linked to neural system dysfunction, 5HT perturbations, and pediatric risk for mood disorders (Gibb et al., 2009, Lau et al., 2009). We examine interaction of maternal depression history and 5HTTLPR genotype in predicting face processing errors in a community sample of adolescents. We hypothesized that youth with a maternal depression history and the low expressing 5HTTLPR genotype would display more errors in identifying facial emotion, relative to youth without these two risk factors. We also hypothesized that symptoms of depression and/or anxiety among the youth would not predict errors. We cast a broad net in our categorization of maternal depressive history in order to evaluate an endophenotype for depression within a general community sample.