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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: M\u00fcnster (MS) nMS\u2009=\u2009104; replication sample W\u00fcrzburg (WZ) nWZ\u2009=\u200981]. 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\u2009T-allele via impaired top-down control of limbic structures remains speculative. Potential association with symptom reduction warrants further research.<\/jats:p>","DOI":"10.1093\/scan\/nsae054","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T22:11:34Z","timestamp":1724278294000},"source":"Crossref","is-referenced-by-count":0,"title":["Impact of <i>NPSR1<\/i> gene variation on the neural correlates of phasic and sustained fear in spider phobia\u2014an imaging genetics and independent replication approach"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9264-5003","authenticated-orcid":false,"given":"Elisabeth J","family":"Leehr","sequence":"first","affiliation":[{"name":"Institute for Translational Psychiatry, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie S","family":"Brede","sequence":"additional","affiliation":[{"name":"Institute for Translational Psychiatry, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joscha","family":"B\u00f6hnlein","sequence":"additional","affiliation":[{"name":"Institute for Translational Psychiatry, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kati","family":"Roesmann","sequence":"additional","affiliation":[{"name":"Institute for Clinical Psychology, University of Siegen , Siegen 57072,","place":["Germany"]},{"name":"Institute for Biomagnetism and Biosignalanalysis, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]},{"name":"Institute for Psychology, Unit for Clinical Psychology and Psychotherapy in Childhood and Adolescence, University of Osnabr\u00fcck 49076,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Gathmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Systems Neuroscience, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg , Wurzburg 97080,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Jungh\u00f6fer","sequence":"additional","affiliation":[{"name":"Institute for Biomagnetism and Biosignalanalysis, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]},{"name":"Otto-Creutzfeld Center for Cognitive and Behavioral Neuroscience, University of M\u00fcnster , M\u00fcnster 48149,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Schwarzmeier","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg , Wurzburg 97080,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian R","family":"Seeger","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg , Wurzburg 97080,","place":["Germany"]},{"name":"Department of General Psychiatry, Centre for Psychosocial Medicine, University of Heidelberg , Heidelberg 69115,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Siminski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg , Wurzburg 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