Examining the relationship among genes, attention bias to emotion, and depression in youth

The investigation of biologically initiated pathways to psychological disorder is critical to advance our understanding of mental illness. Research has suggested that attention bias to emotion may be an intermediate trait for depression associated with biologically plausible candidate genes, such as the serotonin transporter (5-HTTLPR) and catechol-o-methyl-transferase (COMT) genes, yet there have been mixed findings in regards to the precise direction of effects. The experience of recent stressful life events (SLEs) may be an important, yet currently unstudied, moderator of the relationship between genes and attention bias as SLEs have been associated with both gene expression and attention to emotion. Additionally, although attention biases to emotion have been studied as a possible intermediate trait associated with depression, no study has examined whether attention biases within the context of measured genetic risk lead to increased risk for clinical depressive episodes over time. Therefore, this research investigated both whether SLEs moderate the link between genetic risk (5-HTTLPR and COMT) and attention bias to emotion and whether 5-HTTLPR and COMT moderated the relationship between attention biases to emotional faces and clinical depression onset prospectively across 18 months within a large community sample of youth (n= 467). Analyses revealed a differential effect of gene. Youth who were homozygous for the low expressing allele of 5-HTTLPR (S/S) and had experienced more recent SLEs within the last three months demonstrated preferential attention toward negative emotional faces (angry and sad). However, youth who were homozygous for the high expressing COMT genotype (Val/Val) and had experienced more recent SLEs showed attentional avoidance of positive facial expressions (happy). Additionally, youth who avoided negative emotion (i.e., anger) and were homozygous for the S allele of the 5-HTTLPR gene were at greater risk for prospective depressive episode onset. Increased risk for depression onset was specific to the 5-HTTLPR gene and was not found when examining moderation by COMT. These findings highlight the importance of examining risk for depression across multiple levels of analysis, such as combined genetic, environmental, and cognitive risk, and is the first study to demonstrate clear evidence of attention biases to emotion functioning as an intermediate trait predicting depression.