206 II. BIOLOGICAL  FOuNDATIONS
others (mentalizing), and the other involv -
ing feeling emotion in response to others’ 
emotion, which often involves “mirror -
ing”—neural activation that occurs while 
observing another person, in the same net -
works that would be active if the observer 
were having an experience similar to that of 
the observed person. Mentalizing involves 
the default network, primarily, whereas 
mirroring for emotion involves the insula 
and regions of midcingulate cortex, primar -
ily (Andrews-  Hanna et al., 2014; Kanske, 
Böckler, Trautwein, & Singer, 2015; Lamm, 
Decety, & Singer, 2011). Several structural 
MRI studies have found empathy to be posi -
tively associated with cortical thickness or 
volume of the insula (Mutschler, Reinbold, 
Wankerl, Seifritz, & Ball, 2013; Patil et al., 
2018; Sassa et al., 2012; Valk et al., 2016; 
but see Takeuchi, Taki, Sassa, et al., 2014, 
for a failure to replicate), and one study of 
agreeableness indicated that volume of the 
insula and other regions implicated in em -
pathy was specifically related to compassion 
but not politeness (Hou et al., 2017).
One reasonably large study of resting 
functional connectivity found positive asso -
ciations between empathy and connectivity 
among several regions of the default network 
(Takeuchi, Taki, Nouchi, et al., 2014). In an 
even larger sample (over 500 younger adults) 
that included the participants in the con -
nectivity study we just mentioned, empathy 
was negatively correlated with grey matter 
volume in several regions, including many 
of the default network regions that demon -
strated associations between functional con -
nectivity and empathy, and also with a large 
area of dlPFC (Takeuchi, Taki, Sassa, et al., 
2014). Interestingly, a similar negative corre -
lation of volume (and also thickness, in this 
case) of the dlPFC with agreeableness was 
found in the largest study yet to examine all 
of the Big Five in relation to cortical mor -
phometry (Riccelli et al., 2017). Finally, one 
study suggested that functional connectivity 
in the default network was linked not only 
to theory of mind, but also to compassion 
(Allen et al., 2017).
One fMRI study linked agreeableness to 
altruism at the neural level by contrasting 
neural activity in the reward system when 
participants learned that a charity received 
a monetary payment versus when they re -ceived a monetary payment themselves 
(Hubbard, Harbaugh, Srivastava, Degras, 
& Mayr, 2016). This difference was sig -
nificantly correlated with agreeableness, 
indicating part of the biological mechanism 
through which people high in agreeableness 
value good done for others.
Agreeableness is negatively associated 
with levels of the hormone testosterone, 
which has been linked to aggression and 
competition. Testosterone appears to be spe -
cifically linked to low politeness, based on 
research relating testosterone to individual 
differences in interpersonal behavior and 
aggression (De  Young et al., 2013; Montoya, 
Terburg, Box, & Van Honk, 2012; Turan, 
Guo, Boggiano, & Bedgood, 2014). More 
complexly, a study of 216 individuals be -
tween ages 6 and 22 years found that, inde -
pendent of age and sex, testosterone levels, 
aggression, and the covariance of amygdala 
volume and cortical thickness in the medial 
PFC were all mutually interrelated (Nguyen 
et al., 2016). Such a complex finding needs 
replication, of course, but the overlap with 
the substrates of neuroticism in the amygda -
la and medial PFC is notable and may speak 
to the connection between aggression and 
failure to suppress angry or hostile impulses. 
Testosterone may suppress that inhibitory 
control.
Finally, some research suggests that se -
rotonin affects agreeableness (in addition 
to neuroticism and conscientiousness)—
though probably with more influence on po -
liteness (vs. aggression) than on compassion. 
One very small clinical trial in youth ( N = 
12) found that 6 weeks of SSRI treatment 
produced significant reductions in impulsive 
aggression (Armenteros & Lewis, 2002). 
Another study found that serotonergic func -
tioning in young boys with disruptive be -
havioral disorders was negatively associated 
with adolescent aggression and antisocial 
behavior measured 7 years later (Halperin 
et al., 2006). Studies examining assays of 
serotonin in blood or cerebrospinal fluid 
have also suggested a negative association 
between serotonin and traits that reflect low 
agreeableness (Hanna, Yuwiler, & Coates, 
1995; Kruesi et al., 1990; Moul Dobson- 
Stone, Brennan, Hawes, & Dadds, 2013; 
Van Goozen et al., 1999). An interview- 
based measure of life history of aggression 