Physiology & Behavior 143 (2015) 121–135

Contents lists available at ScienceDirect

Physiology & Behavior

journal homepage: www.elsevier.com/locate/phb

Review

Behavioural, hormonal and neurobiological mechanisms of aggressive

behaviour in human and nonhuman primates
Rosa Maria Martins de Almeida ⁎, João Carlos Centurion Cabral, Rodrigo Narvaes
Institute of Psychology, Laboratory of Experimental Psychology, Neuroscience and Behaviour, Federal University of Rio Grande do Sul (UFRGS), 2600 Ramiro Barcelos St, Porto Alegre
90035-003, Brazil

H I G H L I G H T S

• Sex plays an essential role in agonistic behaviours in human and nonhuman primates.
• Testosterone, progesterone, cortisol and vasopressin affect sex-specific aggression.
• Neurotransmitters, mainly GABA and 5-HT, are crucial for sex-specific aggression.
• Positive allosteric modulator of GABAA-R influences sexually dimorphic aggression.
• Neurotransmitter, neuromodulator and hormone relations are the future direction of the field.

a r t i c l e i n f o a b s t r a c t

Article history: Aggression is a key component for social behaviour and can have an adaptive value or deleterious consequences.
Received 6 December 2014 Here, we review the role of sex-related differences in aggressive behaviour in both human and nonhuman pri-
Received in revised form 25 February 2015 mates. First, we address aggression in primates, which varies deeply between species, both in intensity and in dis-
Accepted 28 February 2015
play, ranging from animals that are very aggressive, such as chimpanzees, to the nonaggressive bonobos.
Available online 3 March 2015
Aggression also influences the hierarchical structure of gorillas and chimpanzees, and is used as the main tool
Keywords:
for dealing with other groups. With regard to human aggression, it can be considered a relevant adaptation for
Aggression survival or can have negative impacts on social interaction for both sexes. Gender plays a critical role in aggressive
Agonistic behaviour and competitive behaviours, which are determined by a cascade of physiological changes, including GABAergic
Sex steroids and serotonergic systems, and sex neurosteroids. The understanding of the neurobiological bases and behaviour-
Cortisol al determinants of different types of aggression is fundamental for minimising these negative impacts.
Serotonin neurotransmitter © 2015 Elsevier Inc. All rights reserved.
GABA neurotransmitter

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
2. Aggression in nonhuman primates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
2.1. Species differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
2.2. Sex differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
2.3. Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
3. Human aggression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
3.1. Types of aggressive behaviour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
3.2. Peripheral hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
3.3. Neurobiological mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
3.4. Genetic bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
3.5. Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

⁎ Corresponding author at: Institute of Psychology, Federal University of Rio Grande do Sul, 2600 Ramiro Barcelos St, Porto Alegre, 90035-003 Rio Grande do Sul, Brazil.
E-mail addresses: rosa_almeida@yahoo.com, rosa.almeida@ufrgs.br (R.M.M. de Almeida), centurioncabral@gmail.com (J.C.C. Cabral), rodrigo.narvaes@gmail.com (R. Narvaes).

http://dx.doi.org/10.1016/j.physbeh.2015.02.053
0031-9384/© 2015 Elsevier Inc. All rights reserved.
122 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135
1. Introduction
Aggression is an individual or collective social behaviour that has a
highly adaptive value [1,2]. It may be defined in general terms as a hos-
tile behaviour with the intention of inflicting damage or harm [3]. The
display of agonistic behaviour has evolved in the context of defending
or obtaining resources for almost all species of primates and other
presocial mammals [4–7]. However, among humans, aggression and vi-
olent crimes are considered one of the most serious urban problems
currently faced [8,9]. The remarkable sex differences in aggressive be-
haviour in primates may be explained by natural determinants. The
knowledge on biological and behavioural aspects of this significant sex-
ual dimorphism is essential to be able to not only manage and predict
more accurately the social consequences of aggression, but also for
guidance of public and judicial policies.
Hence, ethological analyses have helped to elucidate the differences
and similarities between human and nonhuman primates, as well as the
phylogenetic origins of social behaviours. The comparative behavioural
sciences have indicated that primates, especially those belonging to the
Hominidae family, present a significant sexually dimorphic pattern of
aggressive behaviour [10]. These data, along with physiological analy-
ses, may clarify the role of sex and gender on aggressive behaviour. Nev-
ertheless, the interdisciplinary nature of the field, and the wide and
continuous effort of the scientific community to deepen understanding
of aggressive behaviour, make the task of synthesising these data a
major challenge, which must constantly be overcome. Here, we propose
the integration of the behavioural, hormonal and neural bases of sex dif-
ferences in aggressive behaviour in both human and nonhuman pri-
mates, along with future directions for aggression research.
2. Aggression in nonhuman primates
Aggressive behaviour is well known as a key element of primate so-
cial behaviour [6]. There are some main contexts in which aggression is
important in primates, e.g. intergroup resource defence, antipredator
behaviour, predation, and intragroup social contexts such as dominance
contests (for food, mates, status etc.) and reproduction [11]. However,
primates also show pathological self-directed aggression as self-
injurious behaviour [11]. Displays of aggression are common in all spe-
cies of primates, and male–male competition associated with physical
aggression is prevalent in all great apes [12].
2.1. Species differences
It is important to differentiate the great apes from the other primates
due to evolutionary differences of the first that might favour aggressive
behaviour — for example, short legs might not only be associated with
better climbing, but also with better stability and stronger impulses in
a fight [13]. Moreover, there are many different social structures
among primates. For example, while chimpanzees (Pan troglodytes)
and bonobos (Pan paniscus) usually live in large groups [14], male
orangutans (Pongo pygmaeus) are extremely intolerant of each other
[15]. Similarly, most encounters involving male gorillas result in dis-
plays of aggression. Among the groups of chimpanzees, aggressive en-
counters are frequent, but the tension inside the group is usually
mended by the reconciliatory behaviour these animals show [14].
Whereas intragroup aggression is stressful, intergroup aggression
poses a much bigger threat to chimpanzees than social stress from hier-
archical ranks. Chimpanzees are known to attack and kill males in other
groups to expand their territories [16,17]. Nonlethal intergroup fights
are widespread in primates, but the pattern of killing males in other
groups is, to this point, recorded only in humans and chimpanzees
[17]. These lethal attacks usually happen when the risk of physical
harm is minimal to the aggressors and where the balance of power
between the groups is extremely asymmetrical. Wrangham and col-
leagues [18] calculated the median risk of violent death in chimpanzees
due to intergroup violence and found that it ranges from 69 to 287 per
100,000 per year, and the victims were mostly adult males (42.4%)
and infants (51.5%). Watts and colleagues [19] report that, while the in-
juries on the aggressors were minimal, the attacked males were report-
ed to have broken bones, wounds covering a considerable part of the
exposed surfaces of the victim, castration and torn thoraxes, despite
resisting intensely [20].
More astonishingly, chimpanzees can also attack humans for various
reasons [21]; these attacks may be due to food deprivation or surprise
encounters between humans and chimpanzees in areas of common
use, such as paths. Most of these attacks were predatory, having chil-
dren as the main targets of the primates. The children were between
18 months and 12 years old, and 7 out of 10 attacks happened when
the children were alone; one happened when a man was present, but
the man had a physical disability. However, once they were pursued
by a human, the attacking chimpanzees would immediately cease the
attack. While the occurrences were rare, Hockings and colleagues [21]
reported that chimpanzees have demonstrated bold behaviour by mov-
ing up to 182 m away from the edge of the forest to capture human
prey; and, on two occasions, a baby was removed from the doorway
of a house.
Unlike chimpanzees, bonobos show extremely low levels of
intragroup aggressive behaviour. Even between groups, they rarely en-
gage in physical aggression, which their phenotype reflects. They have
much smaller canines when compared to their body sizes than those
of chimpanzees and gorillas, and they rarely obtain bone fractures
from interspecific confrontation [13]. There are no known cases of
male–female aggression in bonobos, since females show feeding priori-
ty over males; contrarily from what happens with chimpanzees, the
females always occupy higher ranks in the bonobo hierarchy [22].
Hare and colleagues [22] proposed that this strong reduction in the ex-
pression of the aggressive behaviour in bonobos is due to a natural do-
mestication process that occurred in the species, describing many
phenotypical traits that bonobos share when compared to other domes-
ticated animals that have a “wild counterpart” (i.e., dogs and wolves),
such as reduced cranial size and diminished sexual dimorphism in the
brains and crania when compared to chimpanzees.
While chimpanzees and bonobos usually live in large groups, go-
rillas' groups are much smaller (sometimes even living as lone males)
and have periods of sub- and super-grouping. Lowland, sometimes
called western, gorillas (Gorilla gorilla gorilla) are more frugivorous
and use larger home ranges than the closely-related mountain gorilla
(Gorilla beringei beringei) [23]. Lowland gorillas are also more tolerant
than mountain gorillas to adult males in other groups, even though it
is unusual to have more than one silverback (adult males). In a study
on home-ranges of lowland gorillas, Bermejo [23] found that 50% of
the encounters between his focal group of gorillas and lone males re-
sulted in avoidance, while the other 50% involved aggressive displays.
However, encounters between his focal groups and other groups
showed different results: 64% of the time, the focal group showed toler-
ance, and 14% of the time, the focal group avoided the other groups. The
aggressive encounters corresponded to approximately 21%, with 7% in-
volving physical aggression. Therefore, only a small portion of the en-
counters resulted in aggression, and the silverback gorilla of the focal
group sometimes tolerated other males to the point where they co-
nested, showing a much different behaviour than the more aggressive
mountain gorilla [23]. Mountain gorillas form groups that contain one
or more silverbacks [24], and approximately 40% of the mountain gorilla
groups contain more than one male; however, one single male is likely
to monopolise the reproduction in his group, which is similar to what
happens in the lowland gorilla. Mountain gorillas are not only much
less tolerant than lowland gorillas to males in other groups [23], but
they also perform aggressive displays to females [25]. Interestingly,
the silverbacks from lowland gorilla groups also control the aggression
between the younger members of the group by physically intervening
in conflicts [26], especially in captive groups, where resources, such as
 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135
food and space, are not limited. In fact, conciliatory behaviour has al-
ready been observed in lowland gorillas [27].
Aggression is a very demanding behaviour and has great risks, both
physically and socially. Therefore, the conciliatory behaviour known as
policing is a way of “mending the damages” caused by aggressive be-
haviour inside groups. By definition, policing is the impartial monitoring
and attempted control of conflict among group members that is per-
formed by third parties [28]. Primates show many ways to conciliate
the “brawlers” after aggressive displays or confrontations, and de
Waal [14] has shown that animals that were experimentally induced
to fight, but were then allowed to reconciliate, expressed much more
tolerance to each other than animals that had been prevented from
reconciliating. Other members of the group may also intervene, with fe-
males being the most frequent “catalyst”. Something similar happens in
multimale mountain gorilla groups, as the females, subordinate males
and juveniles intervene in order to prevent two silverbacks from fight-
ing. Captive orangutans frequently engage in aggressive confrontations
and third-party interventions have also been observed [29]. Rhesus
monkeys (Macaca mulatta) also show policing, as described by Beisner
and McCowan [28]. Earlier, McCowan and colleagues [30] analysed the
conflict dynamics of rhesus monkeys and they observed that the behav-
iour of intervening in a fight is an effective way to avoid harsh conse-
quences to the group due to the aggression between its members;
nonetheless, it also bears a great risk to the intervener. However, unlike
what happens with mountain gorillas, the individuals that were found
to be the key interveners were the ones with higher social ranks, and
most of the time (75%), were males.
Stress is another major factor that influences social interactions in
primates. The hierarchical structure and intergroup fights of apes are
sources of stress, and there are clear differences in how stress affects an-
imals in a social hierarchy. In some species, the subordinate animals
show higher levels of stress; in contrast, there are others, like the chim-
panzees, in which the higher ranked animals are more stressed than
those in the lower ranks [31]. Captive rhesus monkeys and feral baboon
groups also show higher stress in high-ranked individuals, but for differ-
ent reasons than chimpanzees. While chimpanzees have to assert their
dominance physically and constantly, captive rhesus macaques and
feral baboons have periods of high social instability, which threatens
the dominant males. Conversely, a considerable part of these studies
was performed with captive animals. It is worth noting that the etholo-
gy of aggression in nonhuman primates and its neuroscience are hard to
conciliate, since there are many behavioural differences in captive and
wild animals. For instance, both cortisol and testosterone not only
show high inter-individual differences, but are also influenced by the
circadian rhythm and environmental factors.
Generally, elevated stress affects cortisol secretion, which is known to
have an impact on aggression when associated with high levels of
testosterone. Cortisol and testosterone are produced by two antagonical
axes: the hypothalamic–pituitary–adrenal (HPA) and the hypothalamic–
pituitary–gonadal (HPG), respectively, which inhibit each other at
different levels creating a complex mechanism that regulates aggressive
behaviour in males [32]. Cortisol in particular is associated with the du-
ration of stress; while acute stress can lead to higher cortisol levels, ani-
mals subjected to chronic stress may not show alterations in the levels of
the hormone [11]. In captive chimpanzees, Yamanashi and colleagues
[33] found a significant and positive correlation between the number
of aggressions received and hair cortisol concentrations. On the other
hand, in females of many species of callitrichids, the cortisol levels appear
not to be associated with stress; instead, the main increase might be re-
lated to endocrine status and reproductive events [34]. Wild common
marmosets showed elevated cortisol levels during late pregnancy [35].
The rise in cortisol levels during late pregnancy was also seen in a
study with captive common marmosets; however, a direct comparison
of mothers (who have a dominant status) and daughters (who are
subordinates) showed no difference in cortisol levels of the two different
social statuses [36]. In a study with a non-callitrichid primate, the ring-
123
tailed lemur, the top ranking females showed higher faecal glucocorti-
coid (GC) levels than the low females in their groups, and the GC levels
were also related to aggressive initiation — the groups and individuals
with higher GC levels were also the ones that usually initiated aggression
[37].
Testosterone is considered one of the main molecules in the regula-
tion of aggressive behaviour and dominance, and it is the final product
of the HPG axis [7,38]. For example, there are changes in the activity
of the HPG axis in olive baboons (Papio anubis) that are dominant or
subordinate males in the social hierarchy; while dominant males have
much higher testosterone levels, subordinate males have decreases in
the basal levels [39]. However, these differences are not always evident;
they become apparent when animals are challenged with an acute
stressor. The mating season is a particularly challenging period in
which males compete with each other for access to sexually receptive
females.
The “Challenge Hypothesis” proposes that testosterone is involved
in the mediation of aggression in periods of heightened conflict be-
tween males [40]. To cope with the increased physical and energetic de-
mands, males undergo raises in both testosterone (according to the
Challenge Hypothesis) and cortisol (the “energy mobilization hypothe-
sis”, as proposed by Romero [41]) levels [42]. The reproductive patterns
are, therefore, extremely relevant to understand how aggressive behav-
iour works in primates. Seasonal breeders, such as the chimpanzees and
the long-tailed macaques (Macaca fuscata) have to cope with one
particular period of time with higher threats and higher rewards for ag-
gression [42]. On the other hand, mantled howler monkeys (Alouatta
palliata) and other nonseasonal breeders do not suffer from stress
spikes throughout the year; rather, their testosterone and cortisol levels
are associated with presence of other groups or solitary males [42]. In
ring-tailed lemurs (Lemur catta), the faecal testosterone levels are
more closely associated with aggression during the mating season,
when social challenges are frequent, than during the most stable period
that precedes mating; besides, faecal testosterone and aggression rate
are correlated in the days of and the day after estrus, but not in the
two days that preceded it. Along with the data from olive baboons,
these findings reinforced the importance of the “Challenge Hypothesis”
as a relevant phenomenon in the behaviour of nonhuman primates [43].
Mantled howler monkeys show much lower rates of aggression than
lemurs, rhesus monkeys and chimpanzees [44], but studies with this
species also corroborate the Challenge Hypothesis. Cristóbal-Azkarate
and colleagues [44] collected faeces from free-ranging resident males
to measure testosterone levels in relation to the number and density
of solitary males. Interestingly, the testosterone levels of resident
males were higher independently of their rank, and the levels were as-
sociated with the number and density of solitary males. These findings
suggest that the appearance of new male in the group had the potential
to negatively affect the reproductive success of all males.
Testosterone is rather associated with competitive behaviours and
dominance than aggression [7]. A study conducted by Steklis and col-
leagues [45] with vervet monkeys (Cercopithecus aethiops sabaeus)
shows that not only the dominant males with higher serum testoster-
one levels were also the ones who initiated aggressive encounters, but
also that the number of encounters won was highly associated with
both aggressive initiation and overall aggression. This phenomenon is
known as the “winning effect”, in which individuals experiencing a re-
ward from its overt aggressive behaviour tend to increase their rates
of agonistic behaviour [45]. Surprisingly, this study also discussed the
idea that testosterone is not directly associated with dominance; rather,
it is associated with the expression of aggressive behaviour in dominant
males.
Measures of faecal androgens levels in wild male golden lion tama-
rins (Leontopithecus rosalia) have shown a much different context
than in other callitrichids. Since golden lion tamarins are cooperative
breeders, subordinate males that are related to the dominant ones do
not show lower levels of faecal androgens, but the cortisol levels of
124 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135
the subordinate males were not significantly different from those of the
dominant ones. Another intriguing finding regarding cortisol levels was
that it tends to drop in individual males when another male moved out
of the natal group and into a breeding position [46]. Therefore, even
though there is a social hierarchy in the golden lion tamarin males, it
is not particularly stressful to neither the dominant and subordinate
males.
Housing conditions in captive primates are also a factor that regu-
lates aggressive behaviour. Animals subjected to poor conditions during
captivity have shown abnormal aggression, including self-injuring be-
haviour [47]. Even though pairing is a way to keep the animal healthier,
sometimes the pairing attempts of animals that were kept in single
cages can result in displays of aggression that might lead to severe
wounds or even death of one of the animals, among other dysfunctional
behaviours [48]. The self-injurious behaviour is a signal of stress, and it
is very hard to stop or revert once it starts [49]. However, Weed and col-
leagues [50] used socialisation as a treatment for this dysfunctional be-
haviour in a rhesus monkey, since neither environmental enrichment
nor changes to the physical environment proved to be effective.
2.2. Sex differences
Aggression is a much more common phenomenon in males than it is
in females due to stronger intrasexual competition and higher payoffs of
escalated aggression [51]. However, reproductive success is also impor-
tant for females, as well as greater access to resources, and females can
also show intense aggression. Female common marmosets (Callithrix
jacchus) were reported to kill other females' infants [52], and female
chimpanzees have been reported to intensely attack immigrant females
and even steal or kill other females' babies [51]. Female chimpanzees
leave their natal groups when they reach sexual maturity, and even
though female–female aggression is a rare event, the immigrants are
regularly attacked by the local females [53].
Even though female aggression directed towards males is much less
common in species were the higher-ranked individuals are males, there
are reports of such phenomenon. One particular study carried out by
Setchell and colleagues [54] describes a very violent cooperative attack
of the females in a semi-free ranging of mandrills (Mandrillus sphinx) to-
wards the alpha of the group after he was injured in a fight against an-
other male. This data shows that even though males dominate the
group and assume a higher-rank position, females can still interfere on
the hierarchy of the group by actively excluding, and even killing, un-
wanted males from the group. Additionally, not only the majority of
the group did not interfere in the attack, but also when one of the
males tried to intervene, the females chased him away.
Females also have a hierarchical structure that affects their food ac-
cess, and, therefore, their offspring survivability [55]. This has been re-
ported in several different research sites, such as Gombe, Kanyawara,
Mahale and Tai [55], but in each place, high-ranking females had differ-
ent advantages. In Tai, females associate at high levels, and high-ranking
females win more contests over food items; in Kanyawara, the high-
ranked females have access to the crowns of the trees, where the best
fruits are located. High-ranking females also have preferential access
to areas with higher food productivity and can inhibit their use by sub-
missive females. Finally, they are more efficient at defending high-
quality core areas.
Kahlenberg and colleagues [53] evaluated the hypothesis that fe-
males do not contest for access to shared food patches; rather, they
compete to occupy the parts of the home range that facilitate long-
term access to preferred food sources. Their results showed that high-
ranked females indeed occupied better neighbourhoods than lower-
ranked females and that rank increased with age. As a result, even
though females are not physically aggressive, they are very competitive,
and competition has a significant influence on the reproductive success
of females. They will, however, use physical aggression against immi-
grant females. Immigrant females receive significantly more aggression
than natal females of the same age, probably because natal females will
emigrate from the group when they reach sexual maturity and, there-
fore, are not long-term competitors to the local females.
Since chimpanzee females emigrate from their natal groups and are
targets of physical aggression when entering new groups, it is not un-
reasonable to wonder how this particular reproductive strategy evolved
as the main behaviour for females. The answer to this puzzling question
lies in male protection of immigrant females. When a female reaches
sexual maturity, their genitals swell, which signals to males that they
are sexually available. While females from other communities are
often attacked by males from different communities [56], immigrant fe-
males are protected from the resident ones by males, creating a conflict
of interest between resident females, who suffer from increased compe-
tition, and resident males who benefit from increased mating opportu-
nities [57].
Rhesus monkeys are the most despotic of the macaques, showing in-
teractions of highly asymmetrical dominance even in the wild, and are
naturally aggressive [58], showing even higher levels of aggression in
captivity. High-ranking females are more likely to be involved in mild
aggression to assert their dominance. However, intense aggression
does not seem to play this role, as high-ranking females were not
more involved in cases of severe aggression than the low-ranking fe-
males [58]. Interestingly, both male and female macaques showed
lower levels of aggression when the enclosures had grass cover instead
of gravel, even during the breeding season. Since rhesus macaques are
very aggressive in the wild, and the physical limitation of space in cap-
tivity exacerbates this behaviour, changing the ground cover of the en-
closure might be a simple way to reduce the potential damage caused
by aggressive outbursts to the communities of captive rhesus.
High ranked rhesus macaques females show differences in the sero-
tonergic function when compared to low ranking females [59]. Females
with higher ranks exhibited higher levels of serotonin metabolite, 5-
hydroxy-indoleic acid (5-HIAA), in the cerebrospinal fluid (CSF) than
lower ranking females, and CSF baselines could be used to predict the
acquisition of social rank. The concentrations also demonstrated to be
stable over time, even in stressful conditions. These results suggest
that adult females show a stable, individual predisposition in the re-
sponse of CNS serotonin (5-HT) and catecholamines.
The effects of estradiol (E2), the primary hormone related to sexual
traits in females, on serum oxytocin, which largely influences pair bond-
ing, maternal care and other social behaviours [60], in females are mod-
ified by their social status and by polymorphisms in the serotonin
transporter genes [61]. E2's role in the regulation of social behaviours
is, in part, likely related to its modulation of 5-HT neural system by in-
creasing 5-HT synthesis and modulating 5-HT reuptake transporter
[61]. This is similar to what happens in males, where testosterone is re-
lated to the serotonergic metabolism [62] and acts in the orbitofrontal
region of the prefrontal cortex, reducing the mRNA levels of the seroto-
nin receptors and the serotonin turnover in the medial prefrontal cortex
[63]. These findings regarding the role of both serotonin and estradiol
align with what is found in humans.
2.3. Perspectives
The ethological work with aggression in nonhuman primates can
help us understand the behaviour of our ancestors, our neurological
foundations to develop aggressive behaviour and the strategies that
the human species developed to cope with aggression in large groups.
While chimpanzees and bonobos are well studied, searching the
keywords “orangutan AND aggression” in three highly renowned data-
bases will yield thirteen results on Scopus, nine results on PubMed and
eleven results on Web of Science, showing the scarcity of studies in the
area. There are many dangers of working with apes, specifically with
highly aggressive ones such as orangutans, but it is worth noting that
knowledge of how orangutans behave in the wild has a major impact
on how they have to be treated in captivity. Orangutans are also
 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135
“endangered” according to the IUCN red list on their website (www.
iucnredlist.org), which increases the urgency of ethological studies
with this species. There are many limitations to these works, but they
should not be seen as impediments; rather, they are opportunities to
develop new methodologies that assess, both directly and indirectly,
the levels of neurotransmitters and their influences on the mechanisms
underlying aggressive behaviour. Neurological research on primates, al-
beit hard to conduct due to behavioural and ethical reasons, is of major
importance to understanding the evolution of human aggression on a
neural basis.
3. Human aggression
Human aggression is a heterogeneous behaviour, influenced by sev-
eral environmental and biological factors. These factors can have adap-
tive benefits or negative impacts as well as anti-social characteristics [2,
64,65]. Aggressive behaviours are associated with adjustment problems
and several psychopathological symptoms such as Antisocial Personali-
ty Disorder (ASPD) [66,67], Borderline Personality Disorder (BPD)
[68–70], Attention Deficit/Hyperactivity Disorder (ADHD) [71,72], In-
termittent Explosive Disorder (IED) [73], Schizophrenia [74,75], and Bi-
polar Mood Disorder (BMD) [76,77]. Some of these disorders have
different incidences for men and women [78–80], but gender differ-
ences are also observed in non-pathological manifestations of aggres-
sive behaviours [2]. This means that gender plays an important role in
human aggression [4,81–83], and there are several theoretical models
that seek to explain this sexual dimorphism among such distinct cul-
tures [84–86]. Therefore, the knowledge of different types of aggression
helps to understand the characteristics underlying gender differences
related to aggressive behaviour.
3.1. Types of aggressive behaviour
Aggression can take a variety of forms; thus, several classifications
and dimensions have been proposed to estimate such differences
[87–90]. A classification often used for human aggression is the way in
which it is expressed and can be subdivided into direct and indirect ag-
gressions. While the first is characterised by physical or verbal behav-
iour intended to cause harm to someone [83,91], the second one is
characterised by a behaviour intended to harm social relations of an in-
dividual or a group [83,88,91]. A significant part of the data on gender
differences in human aggression is based on this classification of both
types of aggression.
Many studies have found differences in aggression types in males
and females. Men tend to have a greater propensity for physical and di-
rect aggression, while women tend to use indirect and verbal aggression
[88,92–96]. Moreover, there is evidence for a greater discrepancy be-
tween genders in school-aged children than in adults [83,93,97], though
there are no differences between genders in preschool-aged children
[98]. Male children and teenagers are more inclined to express direct ag-
gressive behaviour, especially of the physical type, while girls tend to
use indirect aggression and most frequently express social rejection
[92,95,96,99]. However, empirical studies and meta-analyses do not
completely sustain this hypothesis, since several results point towards
little or no difference between genders for indirect aggression [83,84,
97,100]. Furthermore, the female indirect aggression is associated
with the data collection method used [101]. However, such studies
strongly corroborate the male effect towards direct aggression. This
type of aggression is associated with externalising problems, difficulties
in relationships with peers and low prosocial behaviour, on the other
hand, indirect aggression is associated with internalising issues and a
high level of prosocial behaviour [95,101–103]. Moreover, research on
this approach has mainly focused on direct aggression (e.g., [104,
105]), and this can bias or undervalue data on female aggression [101,
102], since this may have evolved to be indirect and physically less
dangerous [4].
125
There is also a functional categorisation, which is useful to under-
stand the psychopathological and neurobiological determining factors
of human aggressiveness. Therefore, the type of aggression that is com-
monly related to an excess or lack of emotional sensitivity [106,107] can
be classified as either impulsive (or reactive) or instrumental (or proac-
tive) aggression [108–110]. Impulsive aggression is defined as a hostile
act in response to a stimuli perceived as threatening or frustrating [111].
This type of aggression has a strong emotional component and high
autonomic arousal [109], besides being associated with low impulse
control [112,113] and a biased perception of hostility [114]. When im-
pulsive aggression is disproportional in relation to the triggering stimu-
lus, it is considered an important psychopathological symptom and
plays a critical role in several psychiatric disorders [115], e.g. in ASPD
and BPD [116,117]. In contrast, instrumental aggression is a deliberately
planned behavioural pattern to attain a goal, and whose actions tend to
be premeditated and controlled [118–120]. This type of agonist behav-
iour is related to the occurrence of delinquency, crime, lack of remorse
and dominance [87,121,122], but also associates with social compe-
tence [108,123] and leadership [106]. Psychopathy, described as a pat-
tern of high occurrence of violent and manipulative behaviours, is
frequently considered a pathological expression of instrumental aggres-
sion [124] besides the lack of remorse and empathy [118]. In this func-
tional categorisation, males once again tend to show higher levels of
aggression in both dimensions, regardless of the age group [91]. Howev-
er, the aggression level of females is also considered to be high, with dif-
ferences that are not always significant between genders, mainly for
impulsive aggression [83,125]. Regardless of the type of aggression, bio-
logical and environmental factors should be considered.
3.2. Peripheral hormones
Several lines of research have sought to explain the gender differ-
ences in aggression based on hormonal physiology, which presents
markedly varied patterns for each gender [126–128,60]. Sex steroid
hormones can play a key role in the manifestation and development
of agonist behaviours [1,129,130]. Testosterone is considered to be the
main androgenic hormone, and it is consistently associated with aggres-
sive behaviour [7,131–133], even in children and adolescents [130,134].
Likewise, early or atypical pre-natal exposure to androgenic steroids can
also have an impact on the development of aggressive behaviour [130,
135–138], particularly in girls [5]. Experimental studies have shown
that supraphysiological levels of testosterone increase the manifesta-
tion of aggression [139–142], while correlation studies associate
testosterone with greater impulsiveness [143,144], greater responsive-
ness of neural circuits related to social aggression [145] and anger
[146–149]. However, these results are not evenly found in all studies
[117,150].
More than aggression, testosterone is strongly related to dominance
behaviour and context of victory in both men and women [5,87,131,
149,151–153]. For men, winning in a competitive situation tends to
increase testosterone levels compared to defeat, but this pattern has
not been observed in women [38,151,154,155]. These studies support
the idea of the winner effect in humans, i.e. there is an increase in ag-
gressiveness and readiness for new confrontations in men that win a
competition, and this effect is highly modulated by the testosterone re-
activity after a victory [38,155,156]. Therefore, it can be assumed that
testosterone is a factor associated with the escalation of aggressiveness
among men, with relevant impact in a competitive context, though this
is not necessarily true for women [127].
The role of testosterone is not fully established in human aggression,
given that several studies have found a weak or inconsistent association
among these variables, in addition to large individual variations for both
genders [5,87,157,158]. This can be explained, in part, by the modulat-
ing effect of cortisol [87,159,160]. Cortisol is the main GC hormone
secreted by humans [161], and chronically elevated levels of this hor-
mone can suppress gonad function and synthesis of androgenic steroids
126 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135
[162]. Reduced levels of cortisol are related to greater aggressiveness
[163], and psychopathic behaviour is related to HPA axis dysfunction
[164–167]. Some studies suggest that testosterone elicits an increase
in aggressiveness [159,160] and competitiveness [168] when combined
with a low level of cortisol. Indeed, the ratio of testosterone and cortisol
can regulate social aggression [32,145]. Also, dehydroepiandrosterone
(DHEA), which is essentially a direct precursor of testosterone, can be
notably relevant for the manifestation of aggressiveness [169], especial-
ly when the levels of testosterone are low [129,170]. High levels of
DHEA and/or its circulating sulphate form (DHEAS) are correlated
with the following: severity of aggressive events [171,172], antisocial
behaviour [173], increased aggression in healthy children [174], as
well as in boys [172] and girls [175] presenting conduct disorder.
The relationship between hormones and aggression is not fully un-
derstood in women compared to men. The inconsistency in the data
on the relationship between female aggression and androgenic steroids
may be explained by the major focus of research on measurement of
physical aggression, which may underestimate female aggression.
Cashdan [127] found greater probability of women with higher levels
of androstenedione, a precursor of sex hormones, to show competitive-
ness through verbal aggression. It was also shown that there was no re-
lationship between androgenic steroids and physical aggression. This
study also indicated that women with higher levels of estradiol had
less competitive interactions. Of note, the ovarian production of testos-
terone, androstenedione and DHEAS reaches the highest levels during
the intermediate period of the menstrual cycle, producing almost
twice the amount of androstenedione than the adrenal glands, besides
all variations in estrogenic hormones [176]. Progesterone, on the other
hand, can interfere with HPA axis function [177–179] and influence ag-
gressive behaviour and emotional lability [78,180]. This may contribute
directly to the controversy of results regarding female aggression and
hormonal secretion.
In this context, both oxytocin and vasopressin are implicated in sex-
typical behaviour [60,181]. Studies with animal models have demon-
strated the key role of vasopressin upon aggressive behaviour [182].
There is a positive association between vasopressin levels and rates of
aggression and impulsivity, having distinct effects on males and females
[183,184]. Additionally, treatment with the V1a vasopressin receptor
antagonist decreases aggression in a dose-dependent manner [182].
On the other hand, these effects of vasopressin may depend on personal
characteristics, such as gender, age and prior social experiences, and on
the type of aggression [183,184]. The scarce human studies on vasopres-
sin suggest social effects similar to those found in animal research. Data
from diverse populations have supported the notion that vasopressin
influences the sexual dimorphism in aggression [185,186]. These stud-
ies have also confirmed that these relations differ for specific types of
aggression. A non-clinical study showed that intranasally delivered
vasopressin differentially affected facial motor patterns in men and
women [181]. In this experiment, the vasopressin enhanced agonistic
and affiliative types of responses towards unfamiliar same-sex faces in
men and women, respectively. A possible explanation suggests that
there is a sex difference in the distribution of vasopressin receptors
[187]. Yet, men would have higher vasopressin levels than women
[188]. It is not completely clear, however, the relationship that vaso-
pressin has with sex steroids on human aggressive behaviour, although
it has been seen that androgenic hormones can strongly influence the
vasopressin receptor binding [187,189,190], and that the vasopressin
induction of aggression is dependent on the presence of testosterone
[191]. Finally, vasopressin influences the HPA axis, mediating the
adrenocorticotropic hormone release, acting synergistically with
corticotropin-releasing hormone function [192,193]; GC can inhibit
the vasopressin synthesis and release [194], but these relationships on
aggressiveness have been mostly neglected. Hormone–neuropeptide
interactions on sex differences in social behaviours have received
more attention only recently; thus, much needs to be elucidated regard-
ing how it influences human aggressiveness.
3.3. Neurobiological mechanisms
The neural basis of aggression has consistently been established in
recent years. Cerebral regions and neurotransmitters, and their connec-
tion with several genes, hormones, and psychiatric disorders, previously
identified in animal models or in studies of lesions, have also been in-
vestigated in healthy people. Among cortical structures, the Prefrontal
Cortex (PFC) is the region that is most extensively associated with im-
pulsive aggression in humans [195,196]. The PFC plays a central role
in the control of behaviours, in driving towards a defined goal and in
the decision-making process [197,198]. A study showed that patients
with ventromedial PFC (vmPFC) lesions had a greater probability of
having verbal conflicts and showing aggressiveness when compared
to patients with lesions in other cerebral areas and a control group
devoid of lesions [199]. In the same study, specific lesions on the
Orbitofrontal Cortex (OFC), the region implicated in auto-regulation
and impulse control [200], were associated with higher aggression
scores. Men with ASPD have shown changes in the OFC, in the Anterior
Cingulate Cortex (ACC), in the Insula and in the Amygdala [201–204].
Likewise, patients with BPD [205,206] and IED [73] also presented atyp-
ical function characteristics in these regions. Neuroimaging studies have
confirmed a dysfunction [73,119,124,207–211] and reduction of the
volume [201,203,204,212,213] of the OFC, ACC and vmPFC in people
with aggressive behaviour. In general, testosterone has been observed
to alter OFC function [145,214–216], which can increase impulsive ag-
gression [207]. This is a possible explanation for the escalation of aggres-
sion caused by the secretion of testosterone after achieving success in a
competition, i.e. the increase of testosterone decreases OFC activity, and
consequently, increases the predisposition to react aggressively in fu-
ture competitions.
There has been growing evidence supporting the amygdala function
as one of the most important regions for aggression in humans [217].
The amygdala, which is involved in the processing of biologically rele-
vant stimuli and emotional reactions [218], and the PFC are reciprocally
connected [219,220]. The OFC regulates the amygdala activity [221],
which is also influenced by sex steroids [126]. Testosterone increases
the neural activity in the amygdala [146,215,222] and hinders its
connectivity with the OFC [214,216]. On the other hand, cortisol has
an inverse correlation with amygdala activation [223]. In other words,
the testosterone/cortisol ratio can increase the bottom-up reaction
(i.e., emphasising amygdala activation) and impair the top-down con-
trol (reducing the inhibitory action of the OFC and ACC) of impulsive ag-
gression. It is important to highlight that amygdala activation can be an
indirect consequence of lack of inhibitory control of the OFC [214]; how-
ever, the direct action of androgenic receptors, present in the PFC [224]
and in the amygdala [225], still requires further elucidation in humans.
Indeed, testosterone exerts its main action through intracellular andro-
genic receptors, although it can also be metabolised to androstenediol,
which modulates the GABAA receptors [226,227] (Fig. 1).
There is a relevant sexual dimorphism in the cerebral structures pre-
viously mentioned [228,229]. Evidence has supported the fact that pro-
gesterone influences amygdala reactivity, with an inverted “U” shaped
relation. This hormone increases the amygdala reactivity in intermedi-
ate doses and decreases it in higher doses, it also emphasises the
amygdala–PFC connectivity; however, in this case the interconnection
with the medial PFC is more affected, which is different from the pattern
related to testosterone [126,216]. Disruptions in the PFC–amygdala con-
nections are associated with many psychiatric disorders [230–232] and
violent acts [73,208,233]. It is worth emphasising that progesterone also
influences GABAA receptors through its metabolite allopregnanolone
[234,235]. Other structures of the limbic system, such as the hippocam-
pus and the hypothalamus, are also highly relevant for aggressive be-
haviour, but causal studies in humans are still scarce.
Similar to data found in preclinical studies, human aggression is re-
lated to the inhibitory action of the GABA neurotransmitter. Alcohol is
a positive allosteric modulator of the GABAA receptor [236], and its
 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135 127

Fig. 1. Steroid hormones and the neurobiology of human aggression. Aggressive behaviour is determined by a cascade of physiological changes, which includes GABAergic and serotonergic
systems, as well as sexual neurosteroids, resulting in amygdala hyperactivation and hypofunction of prefrontal cortex structures (i.e., ventromedial prefrontal cortex, orbitofrontal cortex
and anterior cingulated cortex) responsible for impulse control. Hormones play a key role in human aggression. Intermediate levels of progesterone, high levels of testosterone and low
levels of cortisol are key factors for aggression. The effect of the positive allosteric modulators of GABAA receptors is associated with aggressive behaviours. Intermediate levels of
allopregnanolone and high levels of androstenediol, both endogenous positive modulators of GABAA receptors, can increase aggressiveness. Furthermore, GC can reduce the manifestation
of aggressive behaviour caused by the positive modulators of the GABAA receptor. Decreased serotonergic activity can lead to aggressive behaviour in humans. The density of 5-HT1A re-
ceptors is associated with aggression, mainly with a decrease of its density in the prefrontal cortex and an increase in the raphe nuclei.

recreational intake or abuse often increases the occurrence of aggressive
behaviours [237–239]. This also occurs with most benzodiazepines
when not administered in high doses [240,241]. However, benzodiaze-
pines are also an important class of drugs known for their sedative and
tranquillizer properties [242,243], and are extensively used to restrain
violent patients [244,245]. Bond and colleagues [246] showed that,
even among patients that reported a perceptual decrease in hostility
after eight weeks of treatment with alprazolam, there was an increase
in aggressive responses during a behavioural task. These apparently
controversial results are explained by a dose-dependent action of
these substances on the GABAA receptor, with moderate levels being re-
lated to aggression [247,248]. The paradoxical effect of the endogenous
positive modulators of GABAA receptor has been studied recently, and
several hypotheses have been raised to explain these findings.
Allopregnanolone is the most abundant and efficient endogenous
positive modulator of the GABAA receptor [234,235] and women with
premenstrual dysphoria, besides having low levels of allopregnanolone
during the luteal phase [249–251], still exhibit decreased GABAA recep-
tor sensitivity [252,253]. The order of magnitude for severe or moderate
symptoms in premenstrual dysphoric disorder (PMDD), generally asso-
ciated with irritability and emotional instability [251], is proportional to
that observed in people who are also severely or moderately susceptible
to the paradoxical effects of positive modulators of the GABAA receptor
[254]. This effect suggests an inverted “U” shaped relation [248], as well
as the amygdala reactivity pattern seen for progesterone [126]. More-
over, the serum concentration of allopregnanolone and the administra-
tion of medroxyprogesterone and natural progesterone follow this
same biphasic pattern for the manifestation of negative moods in
women [254]. In rodents, the mRNA expression of 5α-reductase(I), an
enzyme responsible for the biosynthesis of allopregnanolone, is
negatively regulated by the chronic administration of testosterone pro-
pionate in several corticolimbic structures, especially the amygdala
[247]. This data suggests that testosterone reduces the biosynthesis of
allopregnanolone, and it could be a determining factor in gender
differences in aggression; however, these results still need to be demon-
strated in humans.
Stress can be another decisive factor for the sensitivity of the GABAA
receptor to the effects of positive modulators. It has been demonstrated
in animal models that corticosterone (the main GC secreted by rodents
[161]) reduces the manifestation of aggressive behaviour caused by the
positive modulators of the GABAA receptor, including the benzodiaze-
pines and allopregnanolone [255]. In fact, there is evidence associating
the luteal phase in patients with PMDD with deregulation of the HPA
axis [178,249]. In a study performed by Kirschbaum and colleagues
[177], it was observed that, during the luteal phase, women presented
similar secretion levels of cortisol compared to men in response to a
stressful event. These levels were different from those of women in
the follicular phase and women using oral contraceptives. Moreover,
stressful events increase the levels of allopregnanolone [234]. These
findings might help to elucidate the modulation action of cortisol in tes-
tosterone associated-aggression [159,160,207], given the fact that tes-
tosterone can modulate the GABAA receptor [226]. These results lead
to a hypothesis regarding the role of GC in inhibitory feedback for the
escalation of aggressive behaviour. This means that the GC levels rise
after a conflict and can interfere with the endogenous positive modula-
tors of the GABAA receptors, and consequently, reduce impulsive ag-
gression. In addition, this hypothesis can explain the violent behaviour
of psychopathic individuals because the HPA axis is dysfunctional in
these persons, and it can escalate aggression because of a failure in
this inhibitory feedback mechanism.
The serotonergic system is the focus of many lines of research on
aggression and is certainly one of the most important neurotransmitters
in the manifestation of this type of behaviour. Traditionally, dysfunction
of 5-HT activity is related to increased levels of impulsiveness [71,
256–258] and aggressiveness [259,260]. It has been shown that the
use of selective serotonin reuptake inhibitors (SSRI) has a significant
clinical effect in reducing violent behaviour [261–263], and psychiatric
patients with a history of aggression usually have changes in serotonergic
128 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135
neurotransmission [117,257,258,264]. A meta-analysis performed by
Moore and colleagues [265] concluded that the 5-HT metabolite (5-
HIAA) level in the cerebrospinal fluid was consistently low in people
with antisocial behaviour, regardless of psychiatric disorder or gender.
However, recent studies support the idea that the serotonergic action
can also be positively associated with aggressiveness [266,267].
The activation and distribution of different serotonergic receptors
are relevant for their effect on aggressiveness [268]. The presynaptic
somatodendritic 5-HT1A receptors are located in the 5-HT neurones of
the raphe nuclei and postsynaptically in several brain regions, such as
the PFC, amygdala and hippocampus [267,269]. This receptor inhibits
the activity of target neurones and is abundantly expressed in the PFC
[269]. In people with a high level of aggression, there is a greater density
of postsynaptic 5-HT1A receptors in the PFC, including OFC, vmPFC, and
ACC [270], regions related with impulse control. Several studies have
corroborated that the density of the 5-HT transporter (5HTT), as well
as induction of serotonergic stimulation, are associated with changes
in the OFC, vmPFC and ACC in aggressive patients [271–274]. In general,
the cingulated cortex is the cerebral region with the highest density of
serotonergic receptors [275].
There is not much evidence supporting the direct role of 5-HT in
gender differences regarding manifestation of aggression in humans
[265]. However, the serotonergic action in aggressive behaviour can
be regulated by the concentration of sex steroids [270,276]. It is impor-
tant to highlight that the use of an SSRI can increase the levels of
allopregnanolone and attenuate aggression induced by testosterone
propionate, even with the use of doses incapable of inhibiting the
reuptake of 5-HT [247,277]. Variation in the levels of sex hormones
during the menstrual cycle is followed by changes in the distribution
of 5-HT1A receptors [270]. In addition, the use of an SSRI induces an
increase of cortisol in people with high levels of aggression [278]. Also,
5-HT precursors stimulate the secretion of cortisol, as well as several
drugs, including the 5-HT1A receptor agonists [279–281]. On the other
hand, a high secretion of cortisol can interfere with the serotonergic sys-
tem, reducing tryptophan through its interaction with tryptophan
pyrrolase, the main enzyme that metabolises tryptophan [282]. In fact,
low levels of 5-HT, when associated with a high testosterone/cortisol
ratio, can predict the manifestation of aggressive behaviour [32]. Like-
wise, pharmacological and neurobiological findings suggest an interac-
tion between 5-HT and vasopressin in control of aggression [182,283].
An increase in 5-HT yields a fall in vasopressin levels in the anterior
and ventrolateral hypothalamus, along with aggression [185,284]. In
animal models, many brain regions associated with aggressiveness are
known to contain 5-HT and vasopressin activities, like the hypothala-
mus [284], amygdala, PFC and bed nucleus of the stria terminalis
(BNST) [283], which has a role in gender and sex-typical behaviour:
human BNST has a clear sex dimorphism [285]. However, these findings
are incipient to humans, and further studies in this area are definitely
warranted.
3.4. Genetic bases
Many studies approach the genetic influences related to the seroto-
nergic system, as well as the other monoamines, on impulsive aggres-
sion and emotional regulation. Monoamine Oxidase A (MAOA) is an
enzyme involved in the degradation of monoamines, especially 5-HT
[286]. The allele responsible for low expression of MAOA (MAOAL) is
epidemiologically correlated with a higher probability of the occurrence
of aggression and impulsive behaviour [287–289]. A magnetic resonance
neuroimaging study showed structural and functional corticolimbic
alterations related to the MAOAL genotype [290]. Meyer-Lindenberg
and colleagues [290] showed a decrease in the cingulate cortex, insula
and hypothalamus volumes, a hyperactivation of the amygdala and a
hypoactivation of the cingulate cortex and OFC in MAOAL allele carriers
for both genders. Moreover, this study provided evidence for an impor-
tant gender effect, i.e. an increase in the OFC volume and hyperactivation
of the amygdala and hippocampus. An impairment of the amygdala–OFC
connectivity, which occurred only in men with low MAOA expression,
was also observed. Experimental studies have confirmed that low
MAOA activity can predict the occurrence of impulsive aggression as a re-
action to a provocation [291], which can be explained by hypersensitivity
to negative social experiences [292]. Transversal and prospective results
corroborate the deleterious effects of low MAOA activity in males, espe-
cially when it co-occurs with stressful events in childhood [287,289,
293–296]. The MAOA gene is located on the X chromosome [297], causing
a male hemizygous for this gene. Then, the sexual differences in the man-
ifestation of agonist behaviour related to low MAOA activity could be
explained by the X chromosome inactivation in women, a characteristic
that can exacerbate sexual dimorphism [298]. Research on the influence
of MAOA has been particularly relevant for the understanding of gene–
environment interaction, since the role of this enzyme is linked to emo-
tional processing, and occurrence of early exposure to stress leads to an
unfavourable prognosis associated with violence in MAOAL allele carriers
[287,294].
Similar findings have been reported when investigating the role of
the functional polymorphism related to the 5-HT transporter. The 5-
HT transporter gene (5HTTLPR), which is responsible for low transcrip-
tional activity, and consequently, decreased 5-HT reuptake, has been as-
sociated with the occurrence of violent acts [296,299,300]. Other studies
have observed that HTTLPR carriers have decreased ACC and amygdala
volumes, in addition to connectivity impairment among these struc-
tures [301], as well as higher amygdala activity in response to emotional
stimuli [302]. Furthermore, it has been shown that violent individuals
have a lower availability of 5HTT in the ACC region [274]. However,
these results are still incipient and inconclusive for humans. The same
is true for the polymorphism effects of the tryptophan hydroxylase en-
zyme, which has also inconsistently been associated with human ag-
gression, and more empiric evidence is required [303].
3.5. Perspectives
Gender is a factor that plays a key role in human aggression. Crimes
and violent acts have a high prevalence in males [303]. However, social
and cultural aspects may significantly interfere with the distinct expres-
sion of aggressiveness [86]. For example, a high population density,
when associated with a decrease of available resources, might be a sig-
nificant intervening variable for the occurrence of violent acts [304].
Moreover, physical punishment, maladaptive parenting and social isola-
tion can negatively influence the development of aggressive behaviour
in children [287,305]. Gene–environment interactions are critical for
the establishment of pathological aggressiveness [306]. There are
other factors that can also influence human aggressive behaviour and
hinder the comprehension of mechanisms underlying gender differ-
ences. The role of the dopaminergic system, which interacts with 5-HT
[115] and can be modulated directly or indirectly by steroid hormones
[307–309], needs to be properly tested in humans. Similarly, the aroma-
tase activity in the conversion of testosterone into estradiol requires
empiric evidence to corroborate its function in human aggression.
In summary, human aggression can be considered a relevant
evolutionary adaptation for survival and social interaction for both gen-
ders, though, when the reaction is disproportionate to the triggering
stimulus, it can be considered antisocial and maladaptive. Aggressive
behaviour is determined by a cascade of physiological changes, which
includes serotonergic, GABAergic, and dopaminergic systems, as well
as several neurosteroids, resulting in amygdala hyperactivation and
hypofunction of PFC structures responsible for impulse control. The un-
derstanding of the physiological basis and behavioural determinants of
different types of aggression is fundamental for the establishment of
procedures that could minimise the personal and social harm caused
by violent acts. However, findings based on gender patterns and mani-
festations of human aggression are still emerging and require further
research.
 R.M.M. de Almeida et al. / Physiology & Behavior 143 (2015) 121–135 129

4. Conclusions behaviours. The comprehension of the different mechanisms underly-

ing aggression in each gender has grown substantially in the last de-
This review aimed to provide an overview of behavioural, neurobio- cades, and it is a matter of both clinical and ecological importance.
logical and hormonal bases of sex-related differences in aggressive be- Clinically, the elucidation of the physiological pathways associated
haviour (a brief summary is provided in Table 1). Converging evidence with aggression in men and women might allow for differential drug
has identified a key role for the interactions of neurotransmitters, treatments for each case, targeting specific molecules and receptors to
neuromodulators and hormonal systems in aggression and violent maximise efficiency. The knowledge from behavioural and molecular
research has been proven to be significant for improving the under-
Table 1 standing of the origins and determinants of aggression. Thus, here, we
A summary of the main effects of steroid hormones, neuromodulators and neurotransmit- highlighted the major contributions of sex neurosteroids to manifesta-
ters on sexually dimorphic aggressive behaviour. tions of sexual dimorphism of aggression in human and nonhuman pri-
Testosterone (androgenic hormone) mates, alongside with serotonin and GABA neurotransmissions and
genetic factors. However, more data on how these factors can affect
↑ Aggression (in high levels)
↑ Impulsivity and anger early in brain development, both directly or through their interactions
↑ Dominance and competitivity is warranted. Furthermore, the role of dopamine, vasopressin and
↑ Winner effect and readiness for confrontations oxytocin in this interaction issue, as well as the environmental contin-
↓ OFC activity gencies, may help to enhance understanding and expand their applica-
↑ Amygdala activity
↓ OFC–amygdala connectivity
tions for managing and more efficiently avoiding the social costs of
Can be metabolised to androstenediol aggression and violent acts.
↓ Biosynthesis of allopregnanolone

Progesterone (progestogenic hormone) References

↑ Aggression (in intermediated levels)
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Inverted “U” shaped relation with amygdala reactivity
minds: the triple imbalance hypothesis of reactive aggression, J. Pers. 78 (2010)
Affects medial PFC–amygdala connectivity
67–94. http://dx.doi.org/10.1111/j.1467-6494.2009.00609.x.
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