Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes. - PubMed - NCBI
Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes.
Kuhn M1,
Haaker J2,
Glotzbach-Schoon E3,
Schümann D1,
Andreatta M3,
Mechias ML1,
Raczka K1,
Gartmann N1,
Büchel C1,
Mühlberger A4,
Pauli P3,
Reif A5,
Kalisch R6,
Lonsdorf TB1.
Abstract
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. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
KEYWORDS:
amygdala; anxiety; context conditioning; fMRI; hippocampus; nitric oxide synthase
- PMID:
- 26746182
- [PubMed - as supplied by publisher]
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