title: Dexamethasone-induced effects on lymphocyte distribution and expression of adhesion molecules in treatment-resistant depression.
abstract: Alterations in immune function are associated with major depression and have been related to changes in endocrine function. We investigated whether alterations in immune function were associated with altered basal hypothalamic-pituitary-adrenal (HPA) function (salivary cortisol) and lymphocyte sensitivity to dexamethasone (DEX) intake (1 mg PO). The latter was explored by comparing the impact of DEX-induced changes on peripheral lymphocyte redistribution and expression of adhesion molecules (beta2 integrins and L-selectin). The study included 36 inpatients with treatment-resistant major depression (unipolar subtype) and 31 matched healthy controls. The dexamethasone suppression test (DST) was carried out and used to classify 10 patients as HPA axis non-suppressors. The latter presented significantly higher post-DEX salivary cortisol levels than DST suppressors, 82.0 vs. 8.9 nM l(-1) h(-1). No differences in basal salivary cortisol levels were found between patients and controls. Changes in cell redistribution (CD4(+), CD8(+), CD19(+), CD56(+) and HLADR(+) cells) after DEX administration were more prominent in controls than in patients, but the effects of DEX varied dependent on whether patients exhibited DEX-induced suppression of cortisol secretion. Glucocorticoid-induced suppression of adhesion molecule expression was also generally less marked in patients than controls. Our data indicate that alterations in immune function and steroid regulation associated with depression are not related to elevated basal levels of cortisol and further suggest that lymphocyte steroid resistance is associated with drug-resistant depression.
authors.affiliation: Department of Microbiology, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Caixa Postal 1429, 90619-900, Porto Alegre, RS, Brazil. mebauer@pucrs.br
authors.forename: Moisés E
authors.initials: ME
authors.lastname: Bauer
authors.forename: Andrew
authors.initials: A
authors.lastname: Papadopoulos
authors.forename: Lucia
authors.initials: L
authors.lastname: Poon
authors.forename: Paula
authors.initials: P
authors.lastname: Perks
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Stuart
authors.initials: S
authors.lastname: Checkley
authors.forename: Nola
authors.initials: N
authors.lastname: Shanks
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019002:CD56 Antigen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012463:Saliva / Q000737:chemistry; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000928:Antidepressive Agents; D018941:Antigens, CD19; D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D006684:HLA-DR Antigens; D003907:Dexamethasone; D006854:Hydrocortisone