Reduced Serotonin Transporter Availability Decreases Prefrontal Control of the Amygdala
- Inge Volman1,2,
- Lennart Verhagen2,
- Hanneke E. M. den Ouden2,3,
- Guillén Fernández2,4,
- Mark Rijpkema2,5,
- Barbara Franke2,6,
- Ivan Toni2, and
- Karin Roelofs1,2
- 1Behavioural Science Institute, Radboud University Nijmegen, 6525 HR Nijmegen, The Netherlands,
- 2Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 EN Nijmegen, The Netherlands,
- 3Center for Neural Science, New York University, New York, New York 10003, and
- 4Departments of Cognitive Neuroscience,
- 5Nuclear Medicine, and
- 6Human Genetics, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands
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Author contributions: I.V., G.F., I.T., and K.R. designed research; I.V. and L.V. performed research; G.F., M.R., and B.F. contributed unpublished reagents/analytic tools; I.V., L.V., H.E.M.d.O., I.T., and K.R. analyzed data; I.V., L.V., H.E.M.d.O., I.T., and K.R. wrote the paper.
Abstract
After a threatening event, the risk of developing social psychopathologies is increased in short-allele (s) carriers of the serotonin transporter gene. The amygdala becomes overresponsive to emotional stimuli, an effect that could be driven by local hypersensitivity or by reduced prefrontal regulation. This study distinguishes between these two hypotheses by using dynamic causal modeling of fMRI data acquired in a preselected cohort of human s-carriers and homozygous long-allele carriers. Increased amygdala activity in s-carriers originates from reduced prefrontal inhibitory regulation when social emotional behavior needs to be controlled, suggesting a mechanism for increased vulnerability to psychopathologies.
- Received November 30, 2012.
- Revision received April 12, 2013.
- Accepted April 13, 2013.
- Copyright © 2013 the authors 0270-6474/13/338974-06$15.00/0
