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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

Social cognitive and affective neuroscience, 2016-05, Vol.11 (5), p.803-812 [Periódico revisado por pares]

England: Oxford University Press

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Título:
Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes
Autor: 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
Assuntos: Adult ; Amygdala - physiology ; Anxiety - genetics ; Fear - physiology ; Hippocampus - physiology ; Humans ; Magnetic Resonance Imaging ; Medicin och hälsovetenskap ; Nitric Oxide Synthase Type I - genetics ; Original ; Polymorphism, Genetic ; Promoter Regions, Genetic
É parte de: Social cognitive and affective neuroscience, 2016-05, Vol.11 (5), p.803-812
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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.
Editor: England: Oxford University Press
Idioma: Inglês

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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

England: Oxford University Press

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