Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes
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Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes. / Kuhn, Manuel; Haaker, Jan; Glotzbach-Schoon, Evelyn; Schümann, Dirk; Andreatta, Marta; Mechias, Marie-Luise; Raczka, Karolina; Gartmann, Nina; Büchel, Christian; Mühlberger, Andreas; Pauli, Paul; Reif, Andreas; Kalisch, Raffael; Lonsdorf, Tina B.
In: SOC COGN AFFECT NEUR, Vol. 11, No. 5, 05.2016, p. 803-12.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes
AU - Kuhn, Manuel
AU - Haaker, Jan
AU - Glotzbach-Schoon, Evelyn
AU - Schümann, Dirk
AU - Andreatta, Marta
AU - Mechias, Marie-Luise
AU - Raczka, Karolina
AU - Gartmann, Nina
AU - Büchel, Christian
AU - Mühlberger, Andreas
AU - Pauli, Paul
AU - Reif, Andreas
AU - Kalisch, Raffael
AU - Lonsdorf, Tina B
N1 - © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
PY - 2016/5
Y1 - 2016/5
N2 - Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning.
AB - Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning.
KW - Journal Article
U2 - 10.1093/scan/nsv151
DO - 10.1093/scan/nsv151
M3 - SCORING: Journal article
C2 - 26746182
VL - 11
SP - 803
EP - 812
JO - SOC COGN AFFECT NEUR
JF - SOC COGN AFFECT NEUR
SN - 1749-5016
IS - 5
ER -