title: Dexamethasone suppression test identifies a subset of elderly depressed patients with reduced platelet serotonin transport and resistance to imipramine inhibition of transport.
abstract: Dysregulation of the hypothalamus-pituitary-adrenal axis (HPA) is more common in elderly patients with depression than in younger depressed patients, and glucocorticoids are known to influence serotonergic function. Elderly depressed patients are also reportedly more resistant to therapeutic effects of antidepressants. In the current study, we measured platelet serotonin transporter binding sites and transport function in young and elderly depressed patients and determined the relationship to HPA status as assessed with the dexamethasone suppression test (DST). The density and affinity of transporter molecules showed no differences between young and elderly depressed patients, regardless of DST results. Nevertheless, transporter function showed a substantial interaction of aging with DST: elderly DST suppressors showed a deficit in [3H]serotonin uptake capabilities and resistance to imipramine inhibition of uptake. No such defects were seen in the young depressed cohort, regardless of DST status, nor in elderly depressed DST non-suppressors. These results are consistent with the view that depression in the elderly exhibits basic biological differences from depression in earlier life, and that such distinctions may account in part for therapeutic ineffectiveness of antidepressants in specific subgroups, associated with the presence or absence of appropriate HPA regulation.
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA. slotk001@acpub.duke.edu
authors.forename: T A
authors.initials: TA
authors.lastname: Slotkin
authors.forename: J C
authors.initials: JC
authors.lastname: Hays
authors.forename: C B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: B J
authors.initials: BJ
authors.lastname: Carroll
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology / Q000523:psychology*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D001692:Biological Transport; D001792:Blood Platelets / Q000502:physiology; D003866:Depressive Disorder / Q000503:physiopathology*; D003907:Dexamethasone; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011985:Receptors, Serotonin / Q000502:physiology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D005938:Glucocorticoids; D011985:Receptors, Serotonin; D003907:Dexamethasone; D007099:Imipramine