TY  - JOUR
A1  - Juhasz, Gabriella
A1  - Gonda, Xenia
A1  - Hullam, Gabor
A1  - Eszlari, Nora
A1  - Kovacs, David
A1  - Lazary, Judit
A1  - Pap, Dorottya
A1  - Petschner, Peter
A1  - Elliott, Rebecca
A1  - Deakin, John Francis William
A1  - Muir Anderson, Ian
A1  - Antal, Peter
A1  - Lesch, Klaus-Peter
A1  - Bagdy, Gyorgy
T1  - Variability in the effect of 5-HTTLPR on depression in a large European population: the role of age, symptom profile, type and intensity of life stressors
JF  - PLoS ONE
N2  - Background 
Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity. 

Methods 
In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models. 

Results 
The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (\(\leq\)30) individuals. 

Limitations 
Our study is cross-sectional and applies self-report questionnaires. 

Conclusions 
Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups.
KW  - serotonin transporter gene
KW  - environment interaction
KW  - polymorphism
KW  - events
KW  - moderation
KW  - CB1 receptor antagonists
KW  - s allele
KW  - association
KW  - anxiety
KW  - metaanalysis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143703
VL  - 10
IS  - 3
ER  -