title: [Depression and stress: is there an endophenotype?].
abstract: OBJECTIVE
  To review the new findings about stress, hypothalamic-pituitary-adrenal axis and depression trying to explain a possible endophenotype prone to depression.
  
  
  METHODS
  Nonsystematic review of the literature based on the endophenotype hypothesis.
  
  
  RESULTS
  Depression is linked to hypercortisolemia in many patients, but not all patients present these hypothalamic-pituitary-adrenal axis dysfunction. The dexamethasone suppression test is not the most accurate test to measure the hypothalamic-pituitary-adrenal axis function, and its use in the first studies published probably jeopardized the results. Hypercortisolemia frequently occurs in patients with severe depression, melancholic, either psychotic or nonpsychotic type; it is linked to the presence of a polymorphism in the promoter of the serotonin transporter gene, with a history of childhood abuse or neglect, or other significant stressful experiences like the loss of a parent during childhood and temperament leading to alterations in the response to stress.
  
  
  CONCLUSIONS
  The alterations of the hypothalamic-pituitary-adrenal axis depend on many factors like severity and type of depression, genotype, history of exposure to stress, temperament, and probably resilience. All these factors together result in an endophenotype thought to be prone to depression.
authors.affiliation: Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil, and Programa de Pesquisas em Transtornos do Humor, Hospital Butler, USA. amfeijo@uol.com.br
authors.forename: Andrea Feijo
authors.initials: AF
authors.lastname: Mello
authors.forename: Mario Francisco
authors.initials: MF
authors.lastname: Juruena
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Tyrka
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Price
authors.forename: Linda L
authors.initials: LL
authors.lastname: Carpenter
authors.forename: Jose Alberto
authors.initials: JA
authors.lastname: Del Porto
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone; D003865:Major Depressive Disorder / Q000235:genetics* / Q000503:physiopathology; D003907:Dexamethasone; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology; D013694:Temperament
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone