Brief reportVariations in the serotonin-transporter gene are associated with attention bias patterns to positive and negative emotion faces
Introduction
Anxiety is one of the most common and debilitating psychiatric disorders in adulthood. The large personal and societal costs have motivated researchers to find precursors of the disorder that could aid in early identification and intervention. The vast majority of adult cases of anxiety are first evident in childhood (Pine et al., 1998), with a peak incidence in middle to late adolescence (Beesdo et al., 2007). As such, potential risk markers should be detectable early in life. The current paper examined the interrelation between two risk markers, namely attention bias to threat and the serotonin polymorphism (5-HTTLPR), in adolescence. These data may aid researchers in better understanding risk markers that may be at play in the emergence of anxiety.
There is extensive and consistent evidence linking anxiety to persistent biases to threat (Bar-Haim et al., 2007), which may play a causal role in the disorder (Eldar et al., 2008, MacLeod et al., 2004). A parallel literature has demonstrated that allelic variations in 5-HTTLPR also place individuals at increased risk (Lesch et al., 1996). The short allele (S) at 5-HTTLPR for the serotonin-reuptake transporter (SLC6A4) is associated with lower transcriptional efficiency compared to the long allele (L), reducing neurotransmitter availability by approximately 50%.
The data suggest that this reduction amplifies the individual's response to threat, evident in hyper-reactive neuroendocrine (Jabbi et al., 2007, McCormack et al., 2009) and amygdala (Hariri et al., 2002, Kalin et al., 2008) responses in human and animal models (Munafo et al., 2008, Suomi, 2006). Attention biases to threat, when coupled with the S-allele, may act as a parallel cognitive conduit to increased stress reactivity.
Three adult studies have assessed the relations between attention biases and 5HTT genotype employing threat words (Beevers et al., 2007), threatening animals (Osinsky et al., 2008), and emotionally salient pictures (E. Fox et al., 2009) in psychiatric and healthy samples. Two (Beevers et al., 2007, Osinsky et al., 2008) found increased bias toward threat in individuals with at least one S-allele. The third (E. Fox et al., 2009) linked the L-allele to the avoidance of threat and bias toward pictures of happy faces.
To date, one study has examined this potential relation in children (Gibb et al., 2009). Children at high risk due to both maternal depression and the S-allele displayed a non-significant trend of attentional avoidance to sad, but not happy or angry, faces compared to children at low risk.
Clearly, many questions remain concerning the relation between 5-HTTLPR and attention bias toward threatening and appetitive stimuli. This study expands on this research in three ways. First, we focused on adolescents in light of evidence that attention biases may emerge early, before the gradual emergence of anxiety (Pine et al., 2009). Second, our sample size allowed us to examine potential linear trends across three genotype groups (SS/SL/LL). Third, we used ecologically valid and socially relevant stimuli (emotion faces) that influence socioemotional adaptation (Ohman, 2002).
Section snippets
Participants
Participants (N = 138, 66 male) were Caucasian adolescents (Agemean = 15.05 years, SD = 0.97, IQmean = 115.8, SD = 21.9) selected in infancy for a longitudinal study of socioemotional development. Twenty-six were excluded from the final analyses due to poor performance on the task (<63% correct, N = 4), extreme bias scores (>2.5 SDs from mean, N = 5), or missing genotype data (N = 17). The final sample (N = 112, 58 male, Agemean = 14.97, SD = 0.98, IQmean = 117.8, SD = 21.1) did not differ from the excluded participants
Results
One-sample t-tests against zero found significant vigilance to angry faces in adolescents with the low 5HTT neurotransmission genotype (M = 21.16 ms, t(24) = 3.97, p = 0.001, d = 1.62), which diminished as the presumed availability of serotonin increased across the intermediate (M = 9.06 ms, t(49) = 2.33, p = 0.02, d = 0.66), and high (M = 5.12 ms, t(36) = 1.03, p = 0.31, d = 0.34) 5HTT groups (Fig. 1b). The opposite pattern was evident for the happy faces—the attention bias increased from the low (M = −0.49 ms, t(24) =
Discussion
Our findings revealed a linear relation between presumed levels of serotonin availability and the magnitude of attention biases toward both angry and happy faces. Importantly, gene-linked patterns of attention bias were already evident in adolescence—the developmental window during which anxiety often first emerges.
These findings echo recent research demonstrating that anxious adolescents show heightened amygdala activation to threat during a dot-probe task (Monk et al., 2008), and parallel
Conflict of interest
The authors do not have any conflicts of interest, financial or otherwise, to disclose.
Acknowledgments
We would like to thank Stacey Barton, Melissa Ghera, Dalit H. Marshall, and Kirsten VanMeenen for their assistance in data collection. Funding for the study was provided by grants to Nathan A. Fox from the John D. and Catherine T. MacArthur Foundation and NIH (MH074454 and HD17899) and to Koraly Pérez-Edgar from the NIMH (MH073569) and NARSAD (Blowitz-Ridgeway Young Investigator Award).
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2019, Clinical Psychology ReviewCitation Excerpt :Angry faces may indicate social rejection which is theorized to promote depression onset in adults and adolescents who may be especially sensitive to social rejection. Furthermore, the opposite pattern was evident for happy faces; children (mean age of 15) with low transcription efficiency exhibited the least bias for happy faces (Pérez-Edgar et al., 2010). Others have also shown that, compared to children with two long alleles, children with one or two short alleles displayed greater attentional bias to angry faces (ages 8 to 12 years; Gibb et al., 2011) and greater negative schematic processing when exposed to a negative mood induction (aged 7 years; Hayden et al., 2008) than children with two long alleles.