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Impact of NPSR1 gene variation on the neural correlates of phasic and sustained fear in spider phobia: an imaging genetics and independent replication approach

The functional neuropeptide S receptor 1 (NPSR1) gene A/T variant (rs324981) is associated with fear processing. We investigated the impact of NPSR1 genotype on fear processing and on symptom reduction following treatment in individuals with spider phobia. A replication approach was applied [discove...

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Main Authors: Leehr, Elisabeth Johanna (Author) , Brede, Leonie S (Author) , Böhnlein, Joscha (Author) , Roesmann, Kati (Author) , Gathmann, Bettina (Author) , Herrmann, Martin J. (Author) , Junghöfer, Markus (Author) , Schwarzmeier, Hanna (Author) , Seeger, Fabian R. (Author) , Siminski, Niklas (Author) , Straube, Thomas (Author) , Klahn, Anna Luisa (Author) , Weber, Heike Sabine (Author) , Schiele, Miriam A. (Author) , Domschke, Katharina (Author) , Lüken, Ulrike (Author) , Dannlowski, Udo (Author)
Format: Article (Journal)
Language:English
Published: 21 August 2024
In: Social cognitive and affective neuroscience
Year: 2024, Volume: 19, Issue: 1, Pages: 1-11
ISSN:1749-5024
DOI:10.1093/scan/nsae054
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/scan/nsae054
Verlag, kostenfrei, Volltext: https://academic.oup.com/scan/article/19/1/nsae054/7738138?login=true
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Author Notes:Elisabeth J Leehr, Leonie S Brede, Joscha Böhnlein, Kati Roesmann, Bettina Gathmann, Martin J Herrmann, Markus Junghöfer, Hanna Schwarzmeier, Fabian R Seeger, Niklas Siminski, Thomas Straube, Anna Luisa Klahn, Heike Weber, Miriam A Schiele, Katharina Domschke, Ulrike Lueken, Udo Dannlowski
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Summary:The functional neuropeptide S receptor 1 (NPSR1) gene A/T variant (rs324981) is associated with fear processing. We investigated the impact of NPSR1 genotype on fear processing and on symptom reduction following treatment in individuals with spider phobia. A replication approach was applied [discovery sample: Münster (MS) nMS = 104; replication sample Würzburg (WZ) nWZ = 81]. Participants were genotyped for NPSR1 rs324981 [T-allele carriers (risk) versus AA homozygotes (no-risk)]. A sustained and phasic fear paradigm was applied during functional magnetic resonance imaging. A one-session virtual reality exposure treatment was conducted. Change of symptom severity from pre to post treatment and within session fear reduction were assessed. T-allele carriers in the discovery sample displayed lower anterior cingulate cortex (ACC) activation compared to AA homozygotes independent of condition. For sustained fear, this effect was replicated within a small cluster and medium effect size. No association with symptom reduction was found. Within-session fear reduction was negatively associated with ACC activation in T-allele carriers in the discovery sample. NPSR1 rs324981 genotype might be associated with fear processing in the ACC in spider phobia. Interpretation as potential risk-increasing function of the NPSR1 rs324981 T-allele via impaired top-down control of limbic structures remains speculative. Potential association with symptom reduction warrants further research.
Item Description:Gesehen am 06.03.2025
Physical Description:Online Resource
ISSN:1749-5024
DOI:10.1093/scan/nsae054

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