title: Genetics of glucocorticoid regulation and posttraumatic stress disorder--What do we know?
abstract: CASTRO-VALE, I., E.F.C. van Rossum, J.C. Machado, R. Mota-Cardoso and D. Carvalho. Genetics of glucocorticoid regulation and posttraumatic stress disorder-What do we know? NEUROSCI. BIOBEHAV. REV. 43 (1) XXX-XXX, 2014 - Posttraumatic stress disorder (PTSD) develops in a small proportion of those who have been exposed to a traumatic event. Genetic factors are estimated to be responsible for 30% of the variance in PTSD risk. Dysfunction of the hypothalamic-pituitary-adrenal (HPA)-axis in PTSD has been found, particularly hypersensitivity of the glucocorticoid receptor (GR). In this review we aim to understand the genetic factors that influence glucocorticoid function in PTSD. Glucocorticoid action is regulated by a corticotrophin-releasing hormone, arginine vasopressin (AVP)/oxytocin pathway, GR, and regulators such as co-chaperone FKBP5. Single nucleotide polymorphisms (SNPs) in the GR gene, CRHR1 gene and FKBP5 gene affect HPA-axis sensitivity. The GR gene SNP BclI has been associated with hypersensitivity to glucocorticoids and PTSD symptoms. FKBP5 gene SNPs interacted with childhood adversity to moderate PTSD risk and in particular, the rs9470080 SNP was independently associated with lifetime PTSD. SNPs in the CRHR1 gene were also associated with PTSD risk. Gene-environment interaction studies have highlighted the importance of multifactorial vulnerability in PTSD, with epigenetic mechanisms contributing to the equation.
authors.affiliation: Medical Psychology Unit, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. Electronic address: ivonecastrovale@med.up.pt.
authors.forename: Ivone
authors.initials: I
authors.lastname: Castro-Vale
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Internal Medicine, Division of Endocrinology, Rotterdam, The Netherlands. Electronic address: e.vanrossum@erasmusmc.nl.
authors.forename: Elisabeth F C
authors.initials: EF
authors.lastname: van Rossum
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: josem@ipatimup.pt.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Machado
authors.affiliation: Medical Psychology Unit, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: rmc@med.up.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Mota-Cardoso
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. João, Faculty of Medicine University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. Electronic address: davideccarvalho@gmail.com.
authors.forename: Davide
authors.initials: D
authors.lastname: Carvalho
mesh_terms: D001921:Brain / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099052:CRF Receptor, Type 1; D000099159:Tacrolimus Binding Protein 5
chemical_list: D005938:Glucocorticoids; D006854:Hydrocortisone; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099052:CRF Receptor, Type 1; D000099159:Tacrolimus Binding Protein 5; C497713:NR3C1 protein, human
keywords: AVP/oxytocin pathway; FKBP5; Glucocorticoid; Glucocorticoid receptor; HPA-axis; PTSD; Single nucleotide polymorphism; Trauma; Vulnerability