Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Deborah Peeters (Donders series 449)

2 October 2020

Promotors: prof dr. R. Verkes,  prof. dr. J. Homberg

Serotonin and neurocognitive mechanisms of reactive aggression

The neurotransmitter serotonin is important in regulating aggresion, but the functional complexity of the serotonergic system makes the precise role unclear. There is a well known association between low serotonin levels and high aggression, which prompts treatments to increase serotonin with selective serotonin reuptake inhibitors (SSRIs). However, only a subset of patients benefits from this treatment strategy. In an animal study, treatment succes could not be predicted by certain neural and behavioral characteristics, but there was an increased variance on the post-treatment aggression. This suggests there migth still be other predictors. Even though the 5-HT1A receptor density did not predict anti-aggressive SSRI efficacy, high aggression was linked to low 5-HT1A receptor functionality in Tph2 KO rats showing profoundly diminished extracellular serotonin levels. This underlines the importance and complex role of the 5-HT1A receptor in aggression. Moving to clinical studies, high aggressive behavior was shown in female S-allele carriers of the 5-HTTLPR genotype, associated with increased extracellular serotonin levels. This link between aggression and genotype was suggested to depend on the magnitude of participants‘ threat-avoidance tendencies. Furthermore, when impulsive aggressive patients had to avoid threathenig angry faces in a task by pushing a joystick away, they showed increased cortical acitivity. This suggested that these patients may engage a compensatory mechanism that could potentially counteract their increased emotional reactivity.