Effect of Chronic Escitalopram versus Placebo on Personality Traits in Healthy First-Degree Relatives of Patients with Depression: A Randomized Trial

Ulla Knorr,Maj Vinberg,Lars Vedel Kessing,Ulrik Gether,Christian Gluud,Erik Lykke Mortensen,Jørn Wetterslev,Per Winkel,Andreas Reif

doi:10.1371/journal.pone.0031980

Ulla Knorr, Maj Vinberg + Show 7 more

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https://doi.org/10.1371/journal.pone.0031980

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Abstract

IntroductionThe serotonergic neurotransmitter system is closely linked to depression and personality traits. It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. Healthy individuals with a genetic liability for depression represent a group of particular interest when investigating if intervention with SSRIs affects personality. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD).MethodsThe trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. The outcome measure on personality traits was change in self-reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from entry until end of four weeks of intervention.ResultsWhen compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09) versus (−1.32; 7.94), p = 0.046), but not following correction for multiplicity. A trend was shown for increased conscientiousness (p = 0.07). There was no significant effect on subclinical depressive symptoms (p = 0.6).ConclusionIn healthy first-degree relatives of patients with MD, there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness.Trial RegistrationClinicaltrials.gov NCT00386841

Highlights

The serotonergic neurotransmitter system is closely linked to depression and personality traits
In healthy first-degree relatives of patients with major depressive disorder (MD), there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness
Adjustments were planned to be conducted for age, sex, years of education, and concentration of escitalopram in plasma in a general linear model if these variables were associated with change in neuroticism at the 0.1 level of significance [17]

Summary

Introduction

The serotonergic neurotransmitter system is closely linked to depression and personality traits It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD). Neuroticism seems to reflect an enduring vulnerability to major depressive disorder (MD) partly reflecting shared genetic risk factors [1]. It is possible that response to selective serotonin re-uptake inhibitors (SSRIs) may be mediated at least partly via a decrease in neuroticism [4,5]. A recent study from our group has suggested that familial risk of depression and neuroticism interact in their relation to the degree of specific serotonin transporter binding [7]

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