202 II. BIOLOGICAL  FOuNDATIONS
Simplicio, Norbury, Reinecke, & Harmer, 
2014). Similarly, direct administration of se -
rotonin to the hippocampus increases anxi -
ety in studies of nonhuman animals, and 
some forms of depression may even be asso -
ciated with elevated rather than reduced se -
rotonin function (Andrews, Bharwani, Lee, 
Fox, & Thomson, 2015; Dale et al., 2016; 
Gray & McNaughton, 2000). One possi -
bility is that different facets of neuroticism 
are influenced differently by serotonin. The 
two major aspects of neuroticism are with -
drawal  (encompassing anxiety, depression, 
and insecurity) and volatility  (encompassing 
anger, irritability, and emotional lability). 
A recent review suggested that SSRIs might 
have more influence on facets of neuroticism 
reflecting volatility (particularly angry hos -
tility) than on those reflecting withdrawal 
(Ilieva, 2015). Similarly, a recent clinical 
trial in a sample of individuals scoring high 
on hostility found that 2 months of SSRI 
treatment significantly reduced anger and 
irritability (Kamarck et al., 2009).
Openness/Intellect
Openness/intellect (O/I) encompasses a 
broad domain of traits reflecting forms of 
cognitive exploration, including imagina -
tion, curiosity, creativity, aesthetic and in -
tellectual interests, and unconventionality 
(De Young, 2015; De  Young, Grazioplene, 
& Peterson, 2012). Individuals high in O/I 
exhibit heightened preference and ability to 
engage with complex information and are 
more likely to become absorbed in both in -
ward and outward experience. Even more 
than for the other Big Five dimensions, the 
distinction between the two aspects of O/I 
(evident in its compound label) appears to 
be crucial for studying its neural correlates. 
Intellect  reflects engagement with abstract 
or semantic information through reason -
ing, whereas openness to experience  re-
flects engagement with sensory information 
through perception, art, and fantasy (De -
Young, 2015; De  Young et al., 2007). (We 
use “openness” and “intellect” to refer to 
the aspects, while reserving “O/I” for the 
Big Five dimension.) Intellect predicts cre -
ative achievement in the sciences, whereas 
openness predicts creative achievement in the arts (Kaufman et al., 2016). Important -
ly, O/I is the only Big Five trait substantially 
associated with performance tests of intel -
ligence (IQ), and this association is driven 
by variance unique to Intellect (De  Young, 
Quilty, Peterson, & Gray, 2014). The unique 
variance of openness, on the other hand, is 
associated with positive schizotypy (magical 
thinking, unusual thoughts and experiences) 
and hence appears to be a risk factor for psy -
chosis (Chmielewski, Bagby, Markon, Ring, 
& Ryder, 2014, De  Young et al., 2012; De -
Young, Carey, Krueger, & Ross, 2016).
In contrast to extraversion and neuroti -
cism, many of the traits encompassed by 
O/I have no obvious analogue in nonhu -
man animals; no other species creates repre -
sentational art or philosophy, for example. 
However, curiosity appears to provide a 
motivational core to the trait, also seen in 
other species, and curiosity is clearly linked 
to dopamine (Panksepp, 1998). Several lines 
of indirect evidence support the theory that 
O/I is linked to individual differences in do -
pamine function (De  Young, 2013). Whereas 
extraversion is linked to dopaminergic sig -
naling that encodes the value of stimuli, 
research in other mammals suggests that 
curiosity (indexed by exploratory behav -
ior) is linked to a distinct type of dopami -
nergic neurons that encode salience rather 
than value. These neurons increase their fir -
ing rate to stimuli that are both better and 
worse than expected and appear to promote 
information gathering and processing, par -
ticularly via dopaminergic projections to the 
dlPFC (Bromberg-  Martin, Matsumoto, & 
Hikosaka, 2010). O/I has been associated 
behaviorally with reduced latent inhibition 
(an automatic process whereby stimuli pre -
viously deemed irrelevant are blocked from 
awareness), and dopamine decreases latent 
inhibition, suggesting that those high in O/I 
might have a dopaminergically driven ten -
dency to find more information salient (Pe -
terson, Smith, & Carson, 2002).
A recent study tested a hypothesis explic -
itly derived from the dopamine theory of O/I 
(Passamoniti et al., 2015). In fMRI during 
rest, as well as while participants smelled 
pleasant odors and viewed images of food, 
O/I was correlated with functional connec -
tivity between the small region of the mid -
brain where dopaminergic neurons originate 