An investigation of the role of testosterone, cortisol and serotonin in aggression

The hormones testosterone, cortisol and the neurotransmitter serotonin (5-HT)
have been suggested to influence aggressive behavior. For example, the triple
Imbalance hypothesis suggests that individuals that show reactive aggression in
social situations have altered levels of testosterone and cortisol. High levels
of endogenous testosterone and low levels of endogenous cortisol together with
low levels of cortical 5-HT predispose individuals to reactive aggression (van
Honk, et al., 2010). Evidence for this hypothesis is mainly based on animal
research. The research that has been conducted in humans shows that
testosterone is related to antisocial personality disorders and socially
deviant behavior (Stalenheim, Eriksson, von Knorring, & Wide, 1998), and
correlates positively with aggressive acts in male offenders with a personality
disorder (Dolan, Anderson, & Deakin, 2001). High testosterone and also low
cortisol are related to aggressive and approach-related behavior in response to
threat (angry faces; (van Honk, et al., 2010)). Furthermore, psychopathy scores
are associated with a high testosterone (baseline) to cortisol stress response
ratio, but not to these values independently or baseline cortisol (Glenn,
Raine, Schug, Gao, & Granger, 2011). Finally, aggressive behavior in males is
hypothesized to be related to high testosterone combined with low levels of
5-HT (Birger et al., 2003). Serotonergic signaling is affected by a serotonin
transporter polymorphism (5-HTTLPR), of which human short allele carriers
(s-carriers; homozygous and heterozygous) show reduced serotonin transporter
availability and serotonin reuptake (Lesch et al., 1996). This genetic
variation leads to an increased risk for development of social
psychopathologies (Caspi, Hariri, Holmes, Uher, & Moffitt, 2010), such as
aggression-related disorders (Garcia, Aluja, Fibla, Cuevas, & Garcia, 2010).
These studies give some insight in the proposed mechanisms, but a crucial test
of its interactions is lacking. The aim of this study is to test whether
endogenous testosterone and cortisol, and 5-HT interact leading to increased
aggression.
Aggression can be subdivided in instrumental and reactive aggression.
Reactive aggression can be described as premeditated or planned violence, and
is typically not related to impulsive responding to a threat or provocation.
Reactive aggression on the other hand is characterized by such an impulsive,
but not premeditated response (van Honk, et al., 2010). To reliably assess
these facets, several questionnaires related to instrumental and reactive
aggression will be used, next to a set of cognitive experiments. The Taylor
aggression paradigm measures reactive aggression (REF, and can I say this?).
There is no experimental measure of instrumental aggression, but the
approach-avoidance (AA) task has previously been found to be modulated by
instrumental aggression (Von Borries et al., 2012). During the AA task
participants push and pull pictures of angry (and happy) faces using a
joystick, leading to a relative size decrease or increase. This way the
automatic tendency of a participant to avoid or approach that stimulus can be
measured (Von Borries, et al., 2012). If a violent prone participant scores
high on instrumental aggression, he shows an increased relative approach
tendency of angry faces. To control for possible differences in recognition of
facial emotions, an emotion recognition task will also be completed by the
participants.
1. We hypothesize that 5-HTTLPR s-carriers with a high testosterone to
cortisol ratio show increased reactive aggression during the Taylor aggression
paradigm. Homozygous long-allele carriers should not show this effect, and it
should also not be present during the instrumental aggression measures. This
shows that especially the group that is more vulnerable for the development of
psychopathologies (s-carriers) combined with a predisposing hormonal state show
aggression when provoked.
2. As a second, more exploratory step, we will test the influence of other
polymorphisms related to aggression on this hormonal balance, namely SPTLC3
gene; genes encoding estrogen and androgen receptors, MAOA-VNTR, dopamine
transporter and receptor polymorphisms (eg DAT1) (Pavlov, Chistiakov, &
Chekhonin, 2012). We will also explore the effects of testosterone and cortisol
reactivity (reflecting the difference in hormonal levels before and after the
aggression tasks).

Primary Objective: To investigate the role of testosterone, cortisol and
serotonin in aggression (experimentally induced aggression and self-reported
aggression over the last six month).
Secondary Objective(s): the role of approach and avoidance behaviour and
emotion recognition abilities in aggression. Furthermore, questionnaire
measures of social fear, psychopathy, life time events, and mood will be
included to investigate the role of these factors in aggression.

STUDY DESIGN
We will include 200 female students in this study. The study has a
cross-sectional design.
Participation includes filling in questionnaires at home via internet and a
test session at the BSI laboratory of the Radboud University (duration of test
session circa 1,5 hours).

none as it is not an invasive study.