Journal of Psychopharmacology 15(3) (2001) 195–198

©2001 British Association for Psychopharmacology (ISSN 0269-8811)

SAGE Publications, London, Thousand Oaks, CA and New Delhi
0269–8811[200109]15:1;195–198; 018900

Serotonergic involvement in the psychosocial dimension of personality

Wai S. Tse and Alyson J. Bond
Section of Clinical Psychopharmacology, Division of Psychological Medicine, Institute of Psychiatry, King’s College London, UK.

Neurotransmitter systems have been associated with aspects of personality and changes in various
dimensions have been shown after antidepressant treatment. A reduction in harm avoidance and an
increase in self-directedness and cooperativeness, as measured by the Cloninger’s Temperament and
Character Inventory (TCI), have been reported in psychiatric patients receiving treatment with serotonergic
antidepressants. However, some of these changes have been associated with clinical improvement. The
present study therefore used a randomized, double-blind, placebo-controlled design to examine the role of
the serotonergic system on these personality factors in the normal population. Twenty healthy male
volunteers were randomly allocated to either placebo (n = 9) or citalopram treatment (n = 11) for 2 weeks.
Baseline depression and anxiety scores were low and did not differ between groups. The TCI was
administered pre- and post-treatment. There were no baseline differences on any TCI factor between
groups. Citalopram induced a significant increase in self-directedness (p < 0.05) but not cooperativeness or
harm avoidance ratings after treatment. Thus, citalopram has effects on personality aspects which appear to
be separate from its antidepressant properties.
Key words: antidepressant; personality; serotonin

Introduction (SSRIs). The temperament factors have also been found to be

Cloninger (1987) proposed a 3-factor psychobiological model of
temperament. He suggested that there were three temperament
factors; novelty seeking (NS), harm avoidance (HA) and reward
dependence (RD), which were independently heritable and
strongly influenced by different neurotransmitter systems, such as
the dopaminergic, serotonergic and noradrenalinergic systems,
respectively. Subsequently, the number of temperament factors was
amended to four based on the factor analysis approach (Cloninger
et al., 1993). The original RD was split into two factors named
reward dependence (RD) and persistency (P). Cloninger et al.
(1993) also proposed three character factors; self-directedness (S-
DIR), cooperativeness (C), and self-transcendence (S-TRANS),
which they claimed were more likely to be shaped by
developmental processes than by neurobiological factors. Thus, it
was predicted that the temperament factors were more likely to be
changed by pharmacological treatment and the character factors by
psychological intervention.
Consistent with the hypothesis, changes in temperament factors,
especially a reduction in the HA factor, have been consistently
observed in psychiatric patients receiving long-term treatment,
especially that targeting the serotonergic system. For example,
Hellerstein et al. (2000) reported that the HA scores of dysthymic
patients were reduced after 12 weeks treatment with sertraline or
imipramine compared to baseline. Chien and Dunner (1996) also
found HA scores to be reduced in patients with major depression
after treatment with selective serotonin reuptake inhibitors
predictive of treatment outcome (Joyce et al., 1994). Patients with
major depressive disorder (MDD) who were high on both HA and
RD, had a favourable response to treatment with either
clomipramine or desipramine. Temperament explained more of the
variance (up to 50%) than any of the clinical variables. Positive
effects have also been found on the Karolinska Scales of
Personality after SSRI treatment (Ekselius and von Knorring,
1999). Patients with MDD were found to show effects representing
‘normalization’ on the scales after 24 weeks treatment.
In contrast to the prediction by Cloninger et al. (1993), some
studies have found that antidepressant treatment can also affect the
character factors of the TCI, especially the S-DIR and C factors.
For example, Allgulander et al. (1998) reported that increases in S-
DIR and C scores were found after paroxetine treatment in patients
suffering from generalized anxiety disorder. Similar results were
found in patients with unipolar depression who received treatment
with either an SSRI or psychotherapy (Black and Sheline, 1997;
Richter et al., 2000). These findings seem to be inconsistent with
Cloninger’s proposal that neurobiological factors are less
influential on the character dimensions. The aforementioned
studies were all conducted in clinical populations. It is possible
that, because depressed patients are reported to have higher HA
scores and lower S-DIR and C scores generally (Hansenne et al.,
1999; Richter et al., 2000), these factors might be related to illness
as well as trait factors and therefore might be responsive to
antidepressant treatment. On the other hand, the S-DIR and C
factors in normal individuals would be more stable and not be

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Table 1 Mean (SD) baseline depression and anxiety scores and age of the two groups
Placebo (n = 9)
Beck Depression Inventory Total score 9.11 (7.44)
State-Trait Anxiety Inventory Trait total score 43.22 (16.17)
Age 27.56 (4.80)
expected to change. However, although not using the TCI, Knutson
et al. (1998) reported that in a 4-week trial of paroxetine in healthy
volunteers, an increase in cooperative behaviour was shown after
one week. Thus, it is possible that serotonin manipulation could
also induce these character changes in normal healthy volunteers.
The current study was designed to investigate the role of the
serotonergic system on the character factors of S-DIR and C in
healthy controls by the administration of 2 weeks treatment with
citalopram or placebo in a randomized, double-blind study.
Citalopram was chosen as the most selective of the SSRIs currently
available, with minimal effects on other neurotransmitters
compared to paroxetine (Hyttel, 1994). Two weeks administration
time was chosen as being ethically and practically acceptable to
healthy volunteers and a time when downregulation, which may be
critical for clinical effects, has occurred (Stassen and Hell, 1998).
Materials and methods
Subjects
Male volunteers, aged 18–60 years, were recruited from the
Camberwell area of London, UK, by advertisement. Exclusion
criteria were any current diagnosis or history of DSM-IV
psychiatric disorder, current use of prescribed or illicit drugs and
current physical illness. At recruitment, they were asked about
smoking and drinking habits. The study was approved by the
Institutional Ethics Committee. All participants gave their written
informed consent.
Design
The present study was a double-blind, randomized, placebo-
controlled trial. Participants were randomly allocated to daily
treatment with either citalopram 20 mg (n = 11) or matching
placebo tablets (n = 9). They were tested on two separate
occasions, pre- and 2 weeks post-treatment.
Procedures
On the first day of the experiment, volunteers filled in a set of
questionnaires to measure their baseline mood and personality.
Subsequently, they were given a pack of tablets and were asked to
take one per day. To minimize side-effects, they were asked to take
the tablet in the evening for the first week and then, after a
monitoring phonecall, were asked to take it in the morning for the
second week. They were advised not to drink alcohol or take any
medication for the period of the study. On the last day of the
experiment, the volunteers returned to the laboratory to fill in the
personality questionnaire again.
Measures
Depression and anxiety were assessed with the Beck Depression
Inventory (BDI; Beck and Steer, 1987) and the trait version of the
State Trait Anxiety Inventory (STAI; Spielberger et al., 1970).
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JOURNAL OF PSYCHOPHARMACOLOGY 15(3)
Citalopram (n = 11)
4.09 (4.04)
35.64 (7.89)
26.09 (4.09)
Personality was assessed by a short version of the Temperament
and Character Inventory (TCI-125: Cloninger et al., 1994).
Statistical analysis
Descriptive statistics are listed as mean ± SD. Differences between
groups at baseline were analysed by Student’s t-test for
independent samples. Treatment effects on personality were
analysed by repeated measures ANOVA which was performed on
each of the seven factors of the TCI. If a factor–treatment
interaction was observed, Student’s t-test for paired samples was
performed within the two treatment groups. In addition, an
ANCOVA to control for scores at baseline was computed between
the two treatment groups (Table 1).
Results
None of the subjects reported any drinking problems. They were
social drinkers who drank, on average, 3–4 drinks, 2–4 times a
week. There were no differences in drinking patterns between
groups. None of the subjects were heavy smokers. Fifty percent
smoked and consumed less than 5 cigarettes a day. The age and
baseline scores of the volunteers on the BDI and STAI are shown
in Table 1. There were no significant differences between the two
groups on these measures. One of the nine volunteers in the
placebo group showed moderate depression on the BDI
(score = 23). A separate statistical analysis was therefore
performed excluding this volunteer but this did not alter the results.
The pre- and post- treatment scores for the TCI are shown in Table
2. There were no significant differences between groups at baseline
(pre-treatment).
Repeated measures ANOVA showed that only the S-DIR and
the C factors indicated significant factor–treatment interactions
[F(1,18) = 4.59, p = 0.046; F(1,18) = 5.40, p = 0.032,
respectively]. A subsequent t-test for paired samples revealed that
the citalopram treated group showed a significant increase in S-
DIR scores by 2.55 [t(10) = –4.29, p = 0.025, Fig. 1]. However,
citalopram treatment did not induce significant changes in the C
factor scores [t(10) = –1.55, p = 0.152, Fig. 2]. The placebo group
did not show any significant changes on either the S-DIR or the C
factor scores. A significant difference between treatments for the S-
DIR factor [F(1,17) = 6.07, p = 0.025] was also shown on the
ANCOVA.
Discussion
An increase in S-DIR scores was found after 2 weeks citalopram
treatment in healthy male volunteers. This is consistent with
previous research examining the effects of SSRIs on personality
factors in psychiatric populations (Black and Sheline, 1997;
Allgulander et al., 1998; Richter et al., 2000). It could be argued
W.S. TSE AND A.J. BOND: PSYCHOSOCIAL DIMENSION OF PERSONALITY 197

Table 2 Mean (SD) scores on the seven factors of the Temperament and Character Inventory (TCI) before and after treatment for the two
groups
Placebo (n = 9) Citalopram (n = 11)
TCI factor Baseline Post-treatment Baseline Post-treatment

Novelty seeking 13.22 (2.49) 13.44 (2.70) 12.36 (4.82) 12.73 (3.69)
Harm avoidance 6.33 (7.09) 5.89 (5.21) 7.09 (4.70) 7.18 (4.83)
Reward dependence 9.33 (2.50) 8.78 (2.77) 9.00 (2.41) 9.27 (2.94)
Persistency 2.67 (1.66) 3.11 (1.27) 3.27 (1.68) 3.36 (1.43)
Self-directedness 15.44 (6.86) 16.00 (7.14) 16.82 (5.49) 19.36 (4.06)
Cooperativeness 20.22 (3.67) 19.33 (4.24) 20.55 (4.48) 21.27 (4.63)
Self-transcendence 5.44 (3.13) 4.44 (3.61) 5.45 (4.78) 5.00 (5.00)

that the increase in the S-DIR scores was attributable to changes in
depression or anxiety after the treatment. Although such changes
were not measured, this explanation seems unlikely, as the baseline
scores were already low, leaving little room for improvement. In
fact, the placebo group showed higher, but non-significant, levels
of depression and anxiety than the citalopram group. A significant
reduction in HA has been consistently reported to correlate with the
change in depressive symptoms after effective antidepressant
treatment (Kleified et al., 1994; Chien and Dunner, 1996). This
reduction could be an indicator for possible improvement in
depressive or anxiety symptoms. In the present study, no
significant reduction in the HA score was observed in the healthy
male volunteers and, thus, there may have been no major
improvement in mood. The increase in the S-DIR scores might
therefore have been directly attributable to citalopram treatment
and linked to modulation of the serotonergic system.
The absence of a reduction in HA is contrary to the results of
previous clinical studies (Allgulander, et al., 1998; Hellerstein et
al., 2000; Richter et al., 2000). One explanation for this finding is
that low HA baseline scores would be expected in our non-clinical
population. In fact, the HA scores for our sample (see Table 2)
were much lower than those reported (means = 13.5 and 11.0 pre-
and post-treatment) for a depressed sample (Black and Sheline,
1997) making a reduction in scores after citalopram less likely to
be observed. However, further studies with larger sample sizes are
needed to confirm this finding and avoid type II errors.
How the serotonergic system might influence S-DIR behaviour
is uncertain. Cloninger et al. (1993) suggested that the S-DIR
factor contained five subfactors, namely, responsibility versus
blaming, purposefulness versus lack of goal direction,
resourcefulness versus inertia, self-acceptance versus self-striving
and congruent second nature versus incongruent habits. In the
present study, we were not able to find out whether citalopram had
effects equally on all the subfactors or selectively on a few of these
factors because we used the shortened version of the TCI which
only yields one general factor of S-DIR.
In addition, citalopram might exert an effect on the S-DIR
factor through a third variable. One such variable is positive affect.
Three well established constructs have been shown to be associated
with positive affect; self-efficacy, self-esteem and locus of control

Figure 1 Mean scores and 95% confidence intervals on self-directedness

pre- and after 2 weeks treatment in the placebo (n = 9) and citalopram Figure 2 Mean scores and 95% confidence intervals on cooperativeness
(n = 11) groups. A significant difference was shown between the two pre- and after 2 weeks treatment in the placebo (n = 9) and citalopram
groups post-treatment using ANCOVA. (n = 11) groups.

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(Brown and Mankowski, 1993; Treasure et al., 1996; Henson and
Chang, 1998, respectively) and it has been suggested that these
may also relate to the S-DIR factor (Cloninger et al., 1993). Long-
term treatment with SSRI antidepressants has been shown to
induce an increase in positive affect in depressed patients (Barge-
Schaapveld et al., 1995) but such an increase was not confirmed
after 4 weeks treatment with paroxetine in normal healthy
volunteers (Knutson et al., 1998). However, the possibility that the
increase in S-DIR scores after 2 weeks of citalopram could be
related to increased positive affect deserves further attention.
Despite the small sample size and the restriction to male
volunteers, the current study points to some interesting findings.
Future studies with larger sample sizes, or a longer period of
treatment, may reveal more effects and could investigate the
mechanisms of such changes in personality in healthy volunteers
after SSRIs, and whether they are related to different subfactors of
S-DIR, increased positive affect or self-efficacy. The stability of
the induced changes and whether they remit immediately on
cessation of treatment could also be investigated.
Acknowledgements
The TCI-125 was graciously supplied by Dr Robert Cloninger.
Address for correspondence
Wai Shing Tse
Section of Clinical Psychopharmacology
Institute of Psychiatry
De Crespigny Park
London SE5 8AF
UK
Email: spklwst@iop.kcl.ac.uk
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