The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

Reactive aggression after interpersonal provocation is a common behavior in humans. Little is known, however, about brain regions and neurotransmitters critical for the decision-making and affective processes involved in aggressive interactions. With the present fMRI study, we wanted to examine the role of serotonin in reactive aggression by means of an acute tryptophan depletion (ATD). Participants performed in a competitive reaction time task (Taylor Aggression Paradigm, TAP) which entitled the winner to punish the loser. The TAP seeks to elicit aggression by provocation. The study followed a double-blind between-subject design including only male participants. Behavioral data showed an aggression diminishing effect of ATD in low trait-aggressive participants, whereas no ATD effect was detected in high trait-aggressive participants. ATD also led to reduced insula activity during the decision phase, independently of the level of provocation. Whereas previous reports have suggested an inverse relationship between serotonin level and aggressive behavior with low levels of serotonin leading to higher aggression and vice versa, such a simple relationship is inconsistent with the current data.

In neurology, only a few measures have been developed and validated for respondents with cognitive impairment, often showing poorer validity results than studies involving healthy persons. Health-related quality of life assessment should therefore be validated in the specific diseases and, if necessary, combined with a neuropsychological evaluation and a disease-specific health-related quality of life measure.

The A-kinase-anchoring protein 5 (AKAP5), a post-synaptic multi-adaptor molecule that binds G-protein-coupled receptors and intracellular signaling molecules has been implicated in emotional processing in rodents, but its role in human emotion and behavior is up to now still not quite clear. Here, we report an association of individual differences in aggressive behavior and anger expression with a functional genetic polymorphism (Pro100Leu) in the human AKAP5 gene. Among a cohort of 527 young, healthy individuals, carriers of the less common Leu allele (15.6% allele frequency) scored significantly lower in the physical aggression domain of the Buss and Perry Aggression Questionnaire and higher in the anger control dimension of the state-trait anger expression inventory. In a functional magnetic resonance imaging experiment we could further demonstrate that AKAP5 Pro100Leu modulates the interaction of negative emotional processing and executive functions. In order to investigate implicit processes of anger control, we used the well-known flanker task to evoke processes of action monitoring and error processing and added task-irrelevant neutral or angry faces in the background of the flanker stimuli. In line with our predictions, Leu carriers showed increased activation of the anterior cingulate cortex (ACC) during emotional interference, which in turn predicted shorter reaction times and might be related to stronger control of emotional interference. Conversely, Pro homozygotes exhibited increased orbitofrontal cortex (OFC) activation during emotional interference, with no behavioral advantage. Immunohistochemistry revealed AKAP5 expression in post mortem human ACC and OFC. Our results suggest that AKAP5 Pro100Leu contributes to individual differences in human aggression and anger control. Further research is warranted to explore the detailed role of AKAP5 and its gene product in human emotion processing.