Automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression: Associations with childhood trauma and the 5-HTTLPR transporter polymorphism

Abstract

Depression risk genes in combination with childhood events have been associated with biased processing as an intermediate phenotype for depression. The aim of the present conceptual replication study was to investigate the role of biased automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression, in the context of genes (5-HTTLPR polymorphism) and childhood trauma. A naturalistic remitted depressed patients sample (N = 209) performed an Approach-Avoidance Task (AAT) with facial expressions (angry, sad, happy and neutral). Childhood trauma was assessed with a questionnaire. Genotype groups were created based on allele frequency: LaLa versus S/Lg-carriers. The latter is associated with depression risk. We found that remitted S/Lg-carriers who experienced childhood trauma automatically avoided sad facial expressions relatively more than LaLa homozygotes with childhood trauma. Remitted LaLa-carriers who had not experienced childhood trauma, avoided sad faces relatively more than LaLa homozygotes with childhood trauma. We did not find a main effect of childhood trauma, nor differential avoidance of any of the other facial expressions. Although tentative, the results suggest that automatic approach-avoidance tendencies for disorder-congruent materials may be a fitting intermediate phenotype for depression. The specific pattern of tendencies, and the relation to depression, may depend on the genetic risk profile and childhood trauma, but replication is needed before firm conclusions can be drawn.

5HTTLPR Genetic Variant and Major Depressive Disorder: A Review

“…European studies are similar to the others, as they also found a higher frequency of the SL genotype [32]. By analyzing Dutch individuals' genotypes, Fleurkens et al [22] noted that 52% (n = 109) of the research participants had the La/Lg genotype. In another German study by Schneider et al [28], however, had the La/Sa genotype, a result similar to the study conducted in a Canadian population [39,40].…”

“…Although not finding a genotypic association of the present gene with childhood adversity (p = 0.128), depressed S/Lg genotype patients with childhood trauma, compared to those with the La/La genotype, avoided sad facial expressions, even after having their depressive and anxiety symptoms controlled. Furthermore, the S/Lg heterozygous group had less emotional and psychological resilience than the La/La homozygous group; that is, they were less able to deal with their problems, overcome obstacles and resist pressure, whether emotional or psychological [22].…”

“…In order to verify facial expressions in Dutch depressive patients in a context of 5HTTLPR-rs25531 gene polymorphism and childhood trauma, Fleurkens et al [22] found that more than 60% of the studied sample had no trauma in childhood, which may be seen as a confounding factor since the information was obtained by self-report. Although not finding a genotypic association of the present gene with childhood adversity (p = 0.128), depressed S/Lg genotype patients with childhood trauma, compared to those with the La/La genotype, avoided sad facial expressions, even after having their depressive and anxiety symptoms controlled.…”

Negative self-referential processing is associated with genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR): Evidence from two independent studies

“…Nevertheless, the current findings provide further evidence for the connection between 5-HTTLPR variation and biased processing of negative information. An interesting literature is emerging which appears to link the 5-HTTLPR to a range of negative cognitive biases (for a review, see [ 12 , 46 – 48 ], although one should keep in mind that publication bias is likely influencing this literature and meta-analyses likely overestimate the true association between the 5-HTTLPR and negative information processing biases. However, it is important to note that the 5-HTTLPR was not globally associated with negative cognitive bias in the current study, as there was no direct link with biased memory for affective stimuli in either study.…”

Negative self-referential processing is associated with genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR): Evidence from two independent studies

“…Nevertheless, the current findings provide further evidence for the connection between 5-HTTLPR variation and biased processing of negative information. An interesting literature is emerging which appears to link the 5-HTTLPR to a range of negative cognitive biases (for a review, see [12,[46][47][48], although one should keep in mind that publication bias is likely influencing this literature and meta-analyses likely overestimate the true association between the 5-HTTLPR and negative information processing biases. However, it is important to note that the 5-HTTLPR was not globally associated with negative cognitive bias in the current study, as there was no direct link with biased memory for affective stimuli in either study.…”