Psychoticism/Impulsivity/Sensation Seeking/Conscientiousness/Constraint 101personality traits (Heath, Cloninger, & Martin, 1994), but
that for impulsivity is lower (15–40%) albeit significant
(Eysenck, 1983).
Ebstein et al. (1996) were the first to report an association
between the trait of novelty seeking and the gene for the D4
dopamine receptor (D4DR). The longer, usually the 7 repeat
form of the 48 base pair sequence, was associated with high
scores on Cloninger’s NS scale in an Israeli population. An
immediate replication was reported by Benjamin et al. (1996)
in an American population using scales from the NEO that
approximate the NS factor such as Excitement Seeking and
Deliberation (vs. Impulsiveness). Within a year Ebstein and
Belmaker (1997) summarized the rapidly growing literature
reporting two more replications and three failures to repli-
cate. Since then two more failures to replicate have been
reported, one in a Swedish population (Jönsson et al., 1998)
and the other in a New Zealand sample (Sullivan et al., 1998).
One partial replication was reported in Finland (Ekelund,
Lichtermann, Jaervelin, & Peltonen, 1999). The variations in
populations among the studies may have something to do
with the inconsistent results. The distribution of alleles dif-
fers among populations. For instance, in a Japanese popula-
tion the 7 repeat allele was not found but a comparison of the
longer (5 and 6 repeats) with the shorter (2 to 4 repeats) still
showed the former to be more characteristic of high novelty
seekers (Ono et al., 1997).
As with MAO, the association between sensation or nov-
elty seeking and this genetic marker is given some credence
by its association with behavioral traits or disorders charac-
terized by impulsivity and sensation seeking. The longer
form of the D4DR has been found in high proportions of
opiate abusers (Kotler et al., 1997), persons with pathological
gambling disorder (Castro, Ibanez, Torres, Sáiz-Ruiz, &
Fernández-Piqueras, 1997), those with attention-deficit-
hyperactivity disorder (Swanson et al., 1998), and infants
showing less distress in reaction to novel stimuli (Auerbach
et al., 1998).
A comparative study was done on the effects of knocking
out the D4R gene in mice on tests of approach-avoidance in
reaction to novel objects or situations (Dulawa, Grandy, Low,
Paulus, & Geyer, 1999). The D4 knockout mice showed re-
ductions in behavioral response to novelty or a decrease in
novelty related exploration in comparison to D4 intact mice.
Despite some failures of direct replication the association
between novelty seeking and the D4DR receptor gene is
given credence by these extensions to psychopathology and
behavior in humans and mice. The D4DR association ac-
counts for only about 10% of the genetic variation in the
human trait, so other genes are certainly involved. The search
is on for such genes. A crucial question is the functional sig-
nificance of the difference between the alleles associated with
high or low sensation seeking. The D4DR gene is expressed
mainly in the limbic brain regions associated with emotional
and motivational characteristics of sensation seeking.
Dopaminergic activity is certainly involved, as has been pos-
tulated. But the significance of the D4DR gene in this activity
is far from certain. An interesting finding is that the density of
D4 receptors is elevated in brains of schizophrenics and that
this receptor is the primary target for the antipsychotic drug
clozapine (Seeman, 1995).SummaryThe underarousal hypothesis related to E has been more suc-
cessfully applied to this third dimension of personality. Both
EEG and brain imaging studies have found some preliminary
evidence of cortical underarousal related to the P dimension
and impulsivity. Sensation seeking and impulsivity have
been related to the characteristic cortical response to a range
of intensities of stimulation. Disinhibited and impulsive per-
sons show an augmentation of cortical response at high
intensities of stimulation relative to low intensities, whereas
inhibited and constrained individuals show a reducing
pattern, particularly at high intensities. This augmenting-
reducing paradigm of cortical reactivity has been extended to
cats and rats, where it is associated with similar kinds of
behavioral reactions and with other kinds of biological reac-
tivity postulated to be the basis of the behavioral traits in
humans.
The clinical model for this dimension of personality lies in
the psychopathic or antisocial personality disorder. One of
the characteristics of this disorder is a lack of emotional reac-
tivity to stimuli associated with punishment and therefore a
deficit in learning to avoid reacting to such stimuli. This leads
to seeking of high-intensity rewarding stimuli regardless of
the risk involved. It is not surprising that psychopaths are all
high impulsive sensation seekers and share some of the same
biological traits with nonpsychopathic sensation seekers such
as low levels of the monoamine oxidase enzyme and high
levels of testosterone.
One psychopharmacological theory of the P dimension is
that it is based on high dopaminergic reactivity and low sero-
tonergic and noradrenergic reactivity to highly stimulating
situations. The low serotonergic reactivity is particularly re-
lated to the lack of restraint or behavioral inhibition and the
low noradrenergic reactivity to the lack of arousal character-
istic of high P, impulsive, and sensation seeking individuals.
There is some evidence from studies of humans of a weaker
response to serotonin stimulants in high sensation seekers
than in low sensation seekers. There is no demonstrated