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Eighteen individuals with 22q11DS (no history of psychosis or antipsychotic use) and 22 controls underwent [\n                    <jats:sup>18<\/jats:sup>\n                    F]-DOPA PET imaging to assess striatal dopamine synthesis (indexed by Ki\n                    <jats:sup>cer<\/jats:sup>\n                    values) and resting-state fMRI to examine FC. Classification performance using FC, dopamine measures, and their combination was assessed via repeated 10-fold cross-validation. Associations between Ki\n                    <jats:sup>cer<\/jats:sup>\n                    , connectivity, and psychotic symptoms were evaluated using linear regression. FC alone classified 22q11DS with 68% balanced accuracy (p\u2009=\u20090.004), Ki\n                    <jats:sup>cer<\/jats:sup>\n                    alone with 77% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and combined measures with 85% balanced accuracy (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), indicating additive value. The somatomotor and auditory networks contributed most to group discrimination. Across individuals, higher Ki\n                    <jats:sup>cer<\/jats:sup>\n                    was significantly associated with more control-like connectivity profiles (p\u2009=\u20090.011), with significant effects in all striatal subdivisions. No association was found between FC and subclinical psychotic symptoms. This multimodal study demonstrates a significant association between striatal dopamine synthesis capacity and functional brain network architecture in 22q11DS. Higher dopamine synthesis was linked to more normative FC, potentially suggesting FC differences reflect a compensatory, rather than pathogenic role. These findings bridge genetic risk at the 22q11.2 locus with dopamine dysfunction and large-scale networks, offering novel insights into the neurobiology of 22q11DS and related neuropsychiatric risk.\n                  <\/jats:p>","DOI":"10.1038\/s41380-026-03839-2","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:11:00Z","timestamp":1788343860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Striatal dopaminergic function and cortical functional connectivity in 22q11.2 deletion syndrome: an integrative multimodal 18F-DOPA PET and magnetic resonance imaging study"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-896X","authenticated-orcid":false,"given":"Valentina","family":"Mancini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-1789","authenticated-orcid":false,"given":"Maria","family":"Rogdaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-3659","authenticated-orcid":false,"given":"Sameer","family":"Jauhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Moretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3562-0683","authenticated-orcid":false,"given":"Mattia","family":"Veronese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3766-3815","authenticated-orcid":false,"given":"Federico","family":"Turkheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2928-1972","authenticated-orcid":false,"given":"Oliver D.","family":"Howes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-2566","authenticated-orcid":false,"given":"Robert A.","family":"McCutcheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"3839_CR1","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1073\/pnas.262796399","volume":"100","author":"W-J Gao","year":"2003","unstructured":"Gao W-J, Goldman-Rakic PS. 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OH has received investigator-initiated research funding from and\/or participated in advisory\/ speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Delix, Eli Lilly, Elysium, Heptares, Global Medical Education, Invicro, Janssen, Karuna, Lundbeck, Merck, Neumora, Neurocrine, Ontrack\/ Pangea, Otsuka, Sunovion, Teva, Recordati, Roche, Rovi and Viatris\/ Mylan. He was previously a part-time employee of Lundbeck A\/v. SJ has received honoraria for educational talks given for Boehringer-Ingelheim, Sunovian, Janssen, Lundbeck and Recordati. He has consulted for LB Pharmaceuticals Ltd and Boehringer-Ingelheim. He has sat on a funding panel for the Wellcome Trust and advised NICE on treatments for tardive dyskinesia. OH and MV hold a patent application for the use of dopamine imaging as a prognostic tool in mental health (WO2021111116). All other authors declare no biomedical financial interests or potential conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Ethical permission was obtained by London-West London & GTAC Research Ethics Committee and the Administration of Radioactive Substances Advisory Committee (REC no 2004\/6745). All methods were performed in accordance with relevant guidelines and regulations. Following description of the study, informed written consent was obtained by all participants. The research was carried out following the ethical principles outlined in the Declaration of Helsinki, except for pre-registration.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Ethics"}}]}}