TY - JOUR
T1 - A potential role for a genetic variation of AKAP5 in human aggression and anger control
AU - Richter, Sylvia
AU - Gorny, Xenia
AU - Marco-Pallares, Josep
AU - Krämer, Ulrike M.
AU - Machts, Judith
AU - Barman, Adriana
AU - Bernstein, Hans Gert
AU - Schüle, Rebecca
AU - Schöls, Ludger
AU - Rodriguez-Fornells, Antoni
AU - Reissner, Carsten
AU - Wüstenberg, Torsten
AU - Heinze, Hans Jochen
AU - Gundelfinger, Eckart D.
AU - Düzel, Emrah
AU - Münte, Thomas F.
AU - Seidenbecher, Constanze I.
AU - Schott, Björn H.
PY - 2011/12/29
Y1 - 2011/12/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84871262400&partnerID=8YFLogxK
U2 - 10.3389/fnhum.2011.00175
DO - 10.3389/fnhum.2011.00175
M3 - Journal articles
AN - SCOPUS:84871262400
SN - 1662-5161
VL - 5
JO - Frontiers in Human Neuroscience
JF - Frontiers in Human Neuroscience
IS - DEC
M1 - 175
ER -