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As previous work on BOLD signal changes remain equivocal, pharmacological multimodal neuroimaging of energy demands and blood flow (CBF) holds promise due to increased specificity of these signals. This may advance the understanding of the involved pharmacodynamic mechanisms and guide treatment strategies of highly prevalent neuropsychiatric disorders. We combine new techniques of functional positron emission tomography (fPET) with high temporal resolution (3\u2009seconds) using [\n                    <jats:sup>18<\/jats:sup>\n                    F]FDG and simultaneously acquired pseudo-continuous arterial spin labelling (pcASL). Thus, we aimed for a highly quantitative assessment of changes in brain activation following an intravenous SSRI challenge using a randomized, placebo-controlled, double-blind study design. We demonstrate acute drug induced changes in glucose metabolism (K\n                    <jats:sub>i<\/jats:sub>\n                    ) in serotonergic projections, i.e. the striatum and the occipital cortex in 16 healthy volunteers (7 females). In an exploratory analysis, acute effects were observed in the dorsal raphe nucleus. We did not observe corresponding changes in CBF, which suggests that observed SSRI effects are specific to brain energy demands. Our results complement the existing literature on the acute pharmacological effects of SSRIs by providing insights in specific aspects of neuronal activation. Moreover, our findings expand upon the results of existing BOLD fMRI studies and, thus, support the application of this pharmacological neuroimaging protocol in psychopharmacological research.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-03849-2","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:34:51Z","timestamp":1770111291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute effects of selective serotonin reuptake inhibitors on cerebral glucose metabolism and blood flow"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8521-1012","authenticated-orcid":false,"given":"Leo R.","family":"Silberbauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray B.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7344-8071","authenticated-orcid":false,"given":"Gregor","family":"Gryglewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7643-2182","authenticated-orcid":false,"given":"Matej","family":"Murga\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Nics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9739-0724","authenticated-orcid":false,"given":"Godber Mathis","family":"Godbersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-1809","authenticated-orcid":false,"given":"Thomas","family":"Stimpfl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-7580","authenticated-orcid":false,"given":"Andreas","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4222-4083","authenticated-orcid":false,"given":"Marcus","family":"Hacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-9539","authenticated-orcid":false,"given":"Rupert","family":"Lanzenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"3849_CR1","doi-asserted-by":"crossref","unstructured":"Saelens J, Gramser A, Watzal V, Zarate CA, Lanzenberger R, Kraus C Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials. 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Lanzenberger received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET\/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. M. Hacker received consulting fees and\/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, Siemens Healthineers. The remaining authors declare no potential conflict of interest with respect to the research, authorship, and\/ or publication of this article.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"54"}}