Workpackage 8: Pharmaco-challenge and neurobiological studies on oxytonergic and serotonergic transmission
Workpackage leaderProf. Sabine Herpertz |
Participants |
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Objectives and Tasks of the Workpackage
This WP is led by the head of the Department of General Psychiatry, Universitätsklinikum Heidelberg, Frankfurt, M.D. Sabine C. Herpertz. Three studies will be conducted within this WP.
The influence of oxytocin on threat perception in young adults with antisocial personality disorder and sex differences will be investigated within an fMRI study in Heidelberg. Individuals with antisocial personality disorder (ASPD) often show aggressive behavior in social interactions. This aggression partly results from a deficit in social information processing. More precisely, individuals with ASPD have a tendency to act hostile due to misinterpreting social signals from their interaction partners. Importantly, in healthy individuals and in patients with Borderline Personality Disorder (BPD) the neuropeptide oxytocin reduces stress and anxiety in social situations; a decrement of aggression has been reported from the animal model. This project aims at investigating whether the intranasal administration of oxytocin can attenuate the negative social information processing bias in young aggressive adults with ASPD and whether sex may be a moderator of the oxytocin effect.
Sex differences in the influence of serotonergic modulation on emotion regulation in adolescents with conduct disorder will be investigated within an explorative fMRI study in Aachen. In children and adolescents with conduct disorder deficiencies in emotion regulation are frequently observed. Moreover, it has been suggested that the neurobiological foundation of emotion regulation may vary between sexes. The link between the neurotransmitter serotonin and the ability to regulate emotions as well as co-varying aggressive and impulsive behaviors can be considered to be one of the most studied neurobiological relationships in biologically-orientated psychiatric research. Many studies have shown that decreased serotonergic activity in the brain is associated with aggressive and impulsive behavior as well as problems in regulating emotions. One method of changing the availability of serotonin in the human brain is modifying the availability of the amino acid tryptophan, which serves as a substrate for the production of serotonin in the brain. The so-called tryptophan challenge test builds on this mechanism: A single dose of tryptophan is administered to temporarily increase substrate availability for serotonin synthesis in the central nervous system. The effect of this challenge procedure on emotion regulation and its neural correlates will be studied whilst combining challenge administration with an emotion regulation task during a functional MRI scan.
The third aim is to implement animal models of female aggressive behavior (correlations with blood/brain OXT/AVP/5HT neurotransmission and pharmacological interference). At the University of Regensburg, we will develop translational rat models to study conduct disorder in young girls. Using the Female Intruder Test (FIT), we can measure aggressive behaviour in adolescent or young adult female rats. We will test the hypotheses that the neuropeptides oxytocin and vasopressin as well as the classical neurotransmitter serotonin (5-HT), which are strongly involved in various aspects of social behaviour, regulate aggression in a sex-specific manner. We also aim to identify the brain areas in which these factors act. To do so, we use techniques such as in vivo microdialysis, venous blood sampling, immunohistochemistry, receptor autoradiography, in situ hybridization, qPCR, intracerebral and systemic application of pharmacogenic/psychoactive drugs and extensive behavioural observations.