Antidepressants like Prozac may not lift the spirit, but rather allow it to bubble up by reducing the weight of hostility and other negative feelings. The findings, reported in the March American Journal of Psychiatry, offer the first pharmacological evidence that negative and positive feelings may arise from distinct biochemical pathways.

Prozac and similar drugs interfere with the reuptake of serotonin by cells that transmit it, thus making more available to receptors. Because low levels of serotonin metabolites in blood or cerebrospinal fluid have been linked to hostility and aggression in animals and people, scientists have assumed that Prozac and other selective serotonin reuptake inhibitors (SSRIs) suppress such impulses.

Hoping to tease out just how SSRIs influence positive and negative feelings, scientists in the laboratory of Victor Reus and Owen Wolkowitz at the University of California, San Francisco, studied the effects of a drug called paroxetine over 4 weeks on 51 healthy volunteers. The subjects took standard tests measuring "assaultiveness" and "irritability" as well as "positive affect"--good feelings--and "negative affect," or bad feelings.

The researchers found that paroxetine significantly reduced negative affect--such as fear and anger--while having no influence on positive affect, such as extroversion and optimism. That the drug made this differentiation shows positive and negative affect "might be different in neurochemical terms," says the lead author, psychologist Brian Knutson, now at the National Institute on Alcoholism and Alcohol Abuse in Bethesda, Maryland.

The research also is in line with observations by Brown University psychiatrist Peter D. Kramer, author of the best seller Listening to Prozac, that Prozac seems to affect no only depression but traits in nondepressed people, such as vulnerability to stress and low self-esteem. He says these findings raise visions of a world of "cosmetic psychopharmacology," in which healthy people pop pills for a personality boost.

(source: Holden, C. (1998). Prozac makes the glass half full? Science, 279, 1857.)