Conclusion and outlook The summarized findings do not provide an exhaustive and satisfying answer about the genetics of stress response and stress-related disorders. Many single findings are still unconnected, and the restriction of the gene selection to established candidates has retarded our understanding of the complex interplay between genetic factors, stress response, and stress-related

disorders. Sophisticated models, especially those aiming to integrate the findings from basic and clinical research as well as from the different Inhibitors,research,lifescience,medical types of stress-related disorders, are required to close the gap in our knowledge. The new chip-based whole-genome technologies, Affymetrix GeneChip and Illumina Genotyping BeadChip, are powerful tools for this endeavor. With this technology, the advantages of an unbiased approach as provided by linkage analysis, and the statistical power of association studies are combined to identify new candidate genes. However, results from unbiased Inhibitors,research,lifescience,medical approaches are always preliminary, and require validation in confirmatory studies. This means that independent replication studies are needed, but also clinical studies taking gene x gene and gene x environment interactions Inhibitors,research,lifescience,medical into account. For causal inferences,

preclinical experiments are required, including (conditional) genetic modification and Inhibitors,research,lifescience,medical the development of specific compounds as research tools for the protein targets. Finally, text- and information-mining tools, which are already available but have to be further developed, will be very helpful to integrate all findings into sophisticated models delineating the pathways from genes to stress response and stress-related disorders. There is still a long way to go – but the prerequisites for success are more present than ever. Selected abbreviations and acronyms ACTH adrenocorticotropic hormone, corticotropin AVP (arginin) Inhibitors,research,lifescience,medical – vasopressin

CRH corticotropin-releasing hormone DEX dexamethasone GR glucocorticoid receptor HPA hypothalamic-pituitary-adrenocortical MR mineral corticoid receptor RAAS renin-angiotensin-aldosterone system TSST Trier Social Stress Test
The medial prefrontal cortex (PFC) is widely recognized as a site of dysfunction in patients with stress-related disorders,8 particularly MDD. Post-mortem studies of suicide victims’ brains Rutecarpine reveal marked morphological changes – most notably, reduced glia and neuron number in the Alisertib chemical structure ventromedial PFC.9 Similarly, magnetic resonance imaging (MRI) studies demonstrate reduced volume of this area in depressed patients,10 as well as abnormal activity11 The PFC integrates information from multiple brain areas to regulate behavior, thought, and affectsfunctions that are often compromised in MDD patients.