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Abstract
Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From the Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance.
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1 Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands
2 Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands
3 Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands
4 Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands; Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands, 2 Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 3 Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, 4 Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands, 5 Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, The Netherlands, 6 Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands, 7 Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands, 8 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands, and 9 Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands