Interrelationship of age, depression, and central serotonergic function: evidence from fenfluramine challenge studies.
The purpose of this study was to examine the relationship between age-associated changes in central serotonergic function and abnormalities associated with major depression. Under randomized double-blind conditions, prolactin and cortisol responses to the serotonin-releasing agent d,l-fenfluramine hydrochloride (60 mg orally) and placebo were examined in 30 normal subjects (15 men, 15 women; age range 21-84 years) and 39 patients with major depressive disorder, endogenous subtype (14 men, 25 women; age range 29-72 years). In the normal subjects, a significant Age x Challenge x Time interaction was observed in the prolactin response (p = .03). This was primarily due to the elevated prolactin responses of the younger healthy women. Peak minus baseline (delta) prolactin responses were negatively correlated with age (women, p = .004; men, p = .06). In the depressed patients there was no age-related decline in prolactin response to fenfluramine. When depressed and healthy younger subjects were compared, delta prolactin responses to fenfluramine were significantly blunted in young patients with depression (p = .003) irrespective of the significant effect of gender (p = .01), but not in older depressed patients. Cortisol responses to fenfluramine did not reveal consistent effects of age, gender, or diagnosis. Age-related decline in central serotonergic function may make older individuals more vulnerable to depression and possibly render depressive episodes more frequent, more severe, and less amenable to treatment.
Lerer
B
B
Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Gillon
D
D
Lichtenberg
P
P
Gorfine
M
M
Gelfin
Y
Y
Shapira
B
B
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000503:physiopathology; D003866:Depressive Disorder / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D005277:Fenfluramine; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D012016:Reference Values; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors; D012737:Sex Factors
D005277:Fenfluramine; D006854:Hydrocortisone; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors