Kuhn, Manuel and Haaker, Jan and Glotzbach-Schoon, Evelyn and Schuemann, Dirk and Andreatta, Marta and Mechias, Marie-Luise and Raczka, Karolina and Gartmann, Nina and Buechel, Christian and Muehlberger, Andreas and Pauli, Paul and Reif, Andreas and Kalisch, Raffael and Lonsdorf, Tina B. (2016) Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes. SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE, 11 (5). pp. 803-812. ISSN 1749-5016, 1749-5024
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; SEROTONIN TRANSPORTER GENE; FEAR-POTENTIATED STARTLE; CONTEXTUAL FEAR; PSYCHIATRIC-DISORDERS; PROMOTER POLYMORPHISM; PERSONALITY-TRAITS; PREFRONTAL CORTEX; VIRTUAL-REALITY; METAANALYSIS; amygdala; anxiety; context conditioning; fMRI; hippocampus; nitric oxide synthase |
| Subjects: | 100 Philosophy & psychology > 150 Psychology |
| Divisions: | Psychology and Pedagogy > Institut für Psychologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2019 10:37 |
| Last Modified: | 25 Mar 2019 10:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2988 |
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