Personality, thought to be stable over time, changes in healthy people who take a widely-used antidepressant
March 1, 1998
UCSF News Release



The degree to which a person is easy-going or irritable--a personality trait thought to be one of the stable touchstones of identity--can be shifted more toward the easy-going side by a drug used to treat depression, University of California San Francisco researchers report.

The evidence that drugs can act on the brain to change once-stable measures of personality is published in the March issue of the American Journal of Psychiatry by a UCSF research team led by Victor Reus, MD, and Owen Wolkowitz, MD, professors of psychiatry at UCSF, and by postdoctoral fellow Brian Knutson, PhD.

Twenty-three mentally healthy men and women, average age 27, who took the anti-depressant paroxetine for four weeks as part of the study scored lower on survey questionnaires used to measure hostility and exhibited more engaging and cooperative behavior in puzzle-solving tasks with a partner than they did at the beginning of the study.

In comparison, a matching group of study volunteers who took only an inactive placebo pill did not change by these measures.

"Personality, a set of traits and attributes that characterize individuals and that persist throughout life, has been thought to be about fifty to sixty percent attributable to inheritance, a conclusion based in large part on studies of twins reared either together or apart," Reus explains.

"Inherited aspects of personality by definition must have some biological underpinning, but this is the first controlled study of the effects of a drug on a component of personality in people who are not mentally ill," he says. "Our findings lead us to conclude that different aspects of normal personality may be altered by psychopharmaceuticals that act on distinct nerve pathways in the brain."

Other researchers in previous studies found that, in psychiatric patients, low levels of a signaling molecule, the neurotransmitter serotonin, may be related to psychiatric disorders characterized by hostility and aggression, Reus says.  In addition, arsonists, violent criminals and people who die by violent methods of suicide score low on markers of serotonin activity, he adds, and studies of monkeys also indicate that low sociability and high hostility may be associated with low serotonin levels.

The UCSF investigators tracked changes in research subjects by taking measurements at the beginning of the study, after one week, and after four weeks.  After only one week, anti-depressant recipients scored lower on measures of hostility, inversely related to blood levels of the anti-depressant.

"From a societal point of view, the result raises the issue of cosmetic psycho-pharmacology," Reus says.  "To what degree should our expectations include not experiencing any significant distress if a drug is available that can reduce the dimensions of distress?"

The UCSF researchers also measured "affiliative behavior" by gauging how much study participants considered or solicited input from partners in solving a simple spatial puzzle.  The same-sex, puzzle-solving pairs, each with one member of the placebo group and one from the anti-depressant group, were videotaped from behind a one-way mirror.  The researchers determined that degree of cooperativeness in puzzle-solving corresponded to blood levels of paroxetine.

As a scientific control, neither study participants nor the scientists who measured their responses and observed their behavior knew who had received the active drug until the conclusion of the study.

Paroxetine is manufactured by SmithKline Beecham and sold under the brand name Paxil.  It is one of a class of anti-depressant drugs known as selective serotonin re-uptake inhibitors, or SSRIs, which have been in clinical use for a decade.  SSRIs are believed to relieve symptoms of depression by increasing the availability of serotonin required to transmit electrical signals in nerve pathways affecting mood.

The new findings suggest that drugs affecting specific signaling pathways in the brain--pathways affected by serotonin in the case of paroxetine--can lead to changes in particular personality characteristics.

Personality researchers measure differences in human personality by looking at a handful of components, including shyness or gregariousness, patterns of thinking, measures of negative emotionality and measures of positive emotionality.  Previous research has led personality researchers to consider negative and positive emotionality to be independent variables, since a person can tend to be expressive of both negative and positive emotions, of neither type of emotion, or of one type but not the other.

This conventional thinking is buttressed by the current study, in which the researchers found that levels of hostility, and to a lesser extent anxiety and sadness, were related to blood levels of the anti-depressant, while measures of positive emotionality were apparently unaffected by the drug. This result suggests that these different aspects of personality are affected by different biochemical and neural pathways, Reus says.

The study was supported by a National Institute of Mental Health postdoctoral training grant and by a UCSF Research Allocation and Evaluation Grant.

(source: UCSF Medical School News Release)