Abstract
In humans, the short allele of a common polymorphism in the serotonin transporter (5-HTT) gene is associated with a higher risk to develop depression and anxiety disorders. Furthermore, individuals carrying this allele are characterized by negative judgment biases, as they tend to interpret ambiguous information in a more pessimistic way. 5-HTT knockout mice, lacking the 5-HTT gene either homo- or heterozygously, provide a widely used model organism for the study of symptoms related to human anxiety disorders. In the present study, we aimed to prove the anxiety-like phenotype of the 5-HTT mouse model, and to investigate whether 5-HTT genotype also causes differences in judgment bias. While our results confirm that homozygous 5-HTT knockout mice display highest levels of anxiety-like behavior, it was decreased in heterozygous mice. Against our expectations, we did not detect differences in the animals’ judgment bias. These results indicate that at least in mice the association between 5-HTT genotype and judgment bias is not straightforward and that other factors, including multiple genes as well as environmental influences, are implicated in the modulation of judgment biases. More research is needed to gain further insights into their function as potential endophenotypes for psychopathology.
Highlights
Anxiety disorders are among the most prevalent psychiatric disorders, severely compromising an individual’s quality of life (Bandelow and Michaelis, 2015)
The aims of this study were (I) to assess cognitive judgment bias (CJB) as a potential cognitive endophenotype for anxiety disorders in mice varying in their serotonin transporter genotype (5-HTT +/+, +/−, and −/−), and (II) to confirm the anxiety-like phenotype of the mouse model applied
There was a significant main effect of genotype on exploratory locomotion in the Elevated plus maze test (EPM) (sum of open and closed arm entries: F(2,16) = 7.255, p = 0.006, Figure 4A) and in the Open field test (OF) (total distance traveled: F(2,26) = 9.653, p ≤ 0.001, Figure 4B), In the present study, we aimed to investigate the role of judgment biases as potential endophenotypes for anxiety disorders in the 5-HTT mouse model
Summary
Anxiety disorders are among the most prevalent psychiatric disorders, severely compromising an individual’s quality of life (Bandelow and Michaelis, 2015). Among the genetic risk factors, the serotonin transporter (5-HTT) gene constitutes an important candidate, with a common polymorphism in the 5-HTT-linked polymorphic region, appearing in form of either a short (s) or a long (l) allele (Lesch et al, 1996; Gross and Hen, 2004; Canli and Lesch, 2007). Carrying the s-allele has been linked to anxiety-related personality traits and is associated with an increased risk to develop anxiety disorders and depression, especially following adverse life events (Lesch et al, 1996; Mazzanti et al, 1998; Greenberg et al, 2000; Caspi et al, 2003, 2010). Such negative cognitive biases comprise attention (e.g., enhanced attention toward threatening stimuli), memory
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