[Depression and stress: is there an endophenotype?].
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.
Mello
Andrea Feijo
AF
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
Juruena
Mario Francisco
MF
Pariante
Carmine M
CM
Tyrka
Audrey R
AR
Price
Lawrence H
LH
Carpenter
Linda L
LL
Del Porto
Jose Alberto
JA
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
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone