@article{GutknechtPoppWaideretal.2015,
  author    = {Gutknecht, Lise and Popp, Sandy and Waider, Jonas and Sommerlandt, Frank M. J. and G{\"o}ppner, Corinna and Post, Antonia and Reif, Andreas and van den Hove, Daniel and Strekalova, Tatyana and Schmitt, Angelika and Colaςo, Maria B. N. and Sommer, Claudia and Palme, Rupert and Lesch, Klaus-Peter},
  title     = {Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice},
  series = {Psychopharmacology},
  volume    = {232},
  journal   = {Psychopharmacology},
  doi       = {10.1007/s00213-015-3879-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154586},
  pages     = {2429 -- 2441},
  year      = {2015},
  abstract  = {Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{-/-}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{-/-}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{-/-}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{-/-}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.},
  language  = {en}
}
@article{JuhaszGondaHullametal.2015,
  author    = {Juhasz, Gabriella and Gonda, Xenia and Hullam, Gabor and Eszlari, Nora and Kovacs, David and Lazary, Judit and Pap, Dorottya and Petschner, Peter and Elliott, Rebecca and Deakin, John Francis William and Muir Anderson, Ian and Antal, Peter and Lesch, Klaus-Peter and Bagdy, Gyorgy},
  title     = {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},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0116316},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143703},
  pages     = {e0116316},
  year      = {2015},
  abstract  = {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.},
  language  = {en}
}