Neuroticism and extraversion are two of the five primary personality dimensions in the Five-Factor Model of Personality1-3
. Neuroticism refers to a tendency to experience negative emotions and emotional instability; extraversion encompasses social extraversion, dominance, and a tendency to experience positive emotions1-3
. Neuroticism and extraversion are largely independent constructs, as evidenced by correlations between them of −.28 and −.38 in two normative samples4
Results from longitudinal studies have consistently shown that neuroticism predicts both the onset and the chronicity of MDD5-11
. For example, in a study of more than 800 children, precursors of neuroticism measured at age 3 predicted whether these children would develop MDD at age 2111
. In some longitudinal studies, lower levels of extraversion have also predicted the onset of MDD9, 12
, but in other studies this pattern has not been replicated8, 10
Neuroticism and extraversion are both moderately heritable, with genetic factors determining 50-60% of their variance2, 13
. Twin studies have found substantial overlap in the genetic factors that are associated with high neuroticism and those that predispose persons to MDD10, 14-17
. Neuroticism, therefore, appears to reflect much of the genetic vulnerability to MDD10, 16, 17
Research on medical disorders with known causes often focuses on the impact of treatments on these causal factors. Despite the accumulating evidence associating neuroticism and extraversion with a causal path to MDD, little research exists on how SSRI treatment affects these personality risk factors. Patients have reported that SSRIs make them less reactive to stress, less sensitive to rejection, and more outgoing and vivacious18-23
. These descriptions are consistent with decreases in neuroticism and increases in extraversion, but these reports have not come from patients in double-blind, placebo-controlled studies18-22
. In the one published placebo-controlled study of neuroticism change during the SSRI treatment of MDD, Agosti and McGrath did not find that fluoxetine patients reported significantly greater neuroticism reduction than placebo patients24
. However, fewer than half of the patients in that study (42%) completed both treatment and assessment, making these findings difficult to interpret24
. Thus, it remains unclear whether neuroticism and extraversion change in response to SSRI treatment of MDD, above and beyond their natural history and the placebo effect.
When change in personality is reported during SSRI treatment, it is usually assumed to reflect nothing more than the state effect of depression on personality measurement21, 25, 26
. When in depressive episodes, patients often describe themselves as more neurotic and less extroverted than they are in their inter-morbid or pre-morbid states. This is consistent with the idea that there is a state effect of depression on personality measurement5, 6, 8
. The state-effect hypothesis holds that reported personality change during SSRI treatment is just change in state effect: as depression improves, the state effect of depression will decline, and personality measurement will change as a consequence21, 25, 26
. This hypothesis thus regards reported personality change as an inconsequential byproduct of depression improvement. The main evidence for this hypothesis is the finding that personality change correlates with depression improvement during SSRI treatment18, 21
Findings inconsistent with the state effect hypothesis were reported from two studies among healthy subjects without current MDD. In both studies, SSRIs were found to affect behaviors and affects that are closely associated with neuroticism and extraversion27, 28
. Recent findings from neuroscience investigations also support associations between these personality dimensions and the serotonin system. For example, molecular genetic and positron emission tomography (PET) studies have associated neuroticism with serotonin receptor polymorphisms and binding29-31
. Individual studies of neuroticism and the functional polymorphic variants of the serotonin transporter gene have yielded mixed results, but two meta-analyses of these studies have converged on the conclusion that the link is statistically significant32, 33
. Moreover, the serotonin system has been implicated as a substrate for behaviors related to extraversion in numerous animal and human studies27, 28, 34-36
. SSRI treatment, which targets the serotonin system, might thus affect neuroticism and extraversion directly, in a manner that does not depend on its antidepressant effects.
Cognitive therapy (CT), a leading psychosocial treatment of MDD, has been shown to reduce depression symptom severity to a degree similar to that produced by SSRIs37-39
. While some studies of CT have examined pre-treatment personality as predictors of outcome40, 41
, very little theoretical or empirical work exists on how CT might impact neuroticism and extraversion. Although the state-effect hypothesis might also apply to personality changes reported in CT, it is also plausible that CT changes personality through cognitive or behavioral pathways. For example, CT therapists routinely encourage socially withdrawn patients to seek out social interactions, and to test whether these interactions are as unpleasant as they predict. CT also teaches patients to challenge internal and stable negative attributions, such as “I am an inferior person.” Such interventions, if successful, might result in changes in neuroticism and extraversion.
This project examined self-reported personality changes in a randomized, placebo-controlled clinical trial of MDD. In the trial, 240 patients were randomized such that 60 patients received placebo for 8 weeks, 120 patients received paroxetine for 16 weeks, and 60 patients received CT for 16 weeks37
. Our first goal was to test whether paroxetine patients or CT patients reported greater changes in neuroticism and extraversion at week 8, relative to placebo patients.
If paroxetine or CT were observed to produce significantly greater personality change than placebo, our second goal was to test whether such effects could be attributed to between-group differences in depression improvement. We examined this in two ways: a) a linear regression that accounted for depression improvement statistically; and b) a matching analysis in which placebo patients were compared against paroxetine patients matched on amount of depression improvement. The state-effect hypothesis would predict that the between-group differences in personality change would be largely eliminated in both of these analyses.
Our third goal was to examine the state-effect hypothesis by analyzing data obtained from the patients assigned to eight weeks of treatment with placebo. In studies of MDD treatments, placebo patients tend to experience substantial improvement in depression42-46
. Thus, their personality data provide a direct test of the state-effect hypothesis, which predicts that these placebo patients should also report substantial change in personality. Because this test is not confounded by the effects of active treatments, it might be the cleanest method to test this hypothesis. Moreover, during the eight weeks that followed the placebo phase, 31 placebo patients accepted the offer of free subsequent treatment with an SSRI. This set up a within-subject comparison between their placebo phase and their SSRI phase. The state-effect hypothesis predicts that the magnitude of reported personality change during each phase should be roughly proportional to the magnitude of depression improvement during that same phase.
Our final goal was to examine whether reported neuroticism reduction during SSRI (or CT) treatment predicted subsequent relapse, since neuroticism is a key risk factor that reflects much of the genetic cause of MDD. If reported neuroticism reduction during active treatment was merely a change in the state effect of depression, then it should have no long-term clinical consequences.