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Reductions in hippocampal GABAergic neurons have been found in schizophrenia, and increased hippocampal perfusion has been described in schizophrenia and in people at clinical high-risk for psychosis (CHRp). We have also found decreases in hippocampal GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors containing the \u03b15 subunit (GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b15) in a well-validated neurodevelopmental rat model of relevance for schizophrenia. Positive allosteric modulation of these receptors in the hippocampus using a specific compound was shown to reverse the behavioural and neurophysiological phenotypes of this model. However, whether GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b15 availability is dysregulated in the psychosis spectrum at the regional or network levels is unknown. We addressed this issue by using [\n                    <jats:sup>11<\/jats:sup>\n                    C]Ro15-4513 and positron emission tomography (PET) in 22 individuals at CHRp, 10 people with a first-episode psychosis (FEP) and 23 healthy controls (HC). We quantified GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b15 availability in the hippocampus and across the brain, and employed a perturbation covariance method to assess individual molecular covariance deviations in CHRp and FEP groups compared to the HC group. Hippocampal GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b15 availability was not significantly different between groups (\n                    <jats:italic>F<\/jats:italic>\n                    (2,50)\u2009=\u20090.25, p\u2009=\u20090.78). However, network analysis identified significant deviations in GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b15 covariance between groups, both across all regions (all p\u2009&lt;\u20090.001, pairwise Cohen\u2019s d\u2009=\u20090.07\u20130.5) and relative to the hippocampus (all p\u2009&lt;\u20090.001, pairwise Cohen\u2019s d\u2009=\u20090.01\u20130.67). These findings suggest that individuals at clinical high-risk for psychosis and people with early psychosis may show alterations to the brain-wide organisation of the GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b15 system, rather than changes at a regional level.\n                  <\/jats:p>","DOI":"10.1038\/s41380-025-03204-9","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T06:00:41Z","timestamp":1757138441000},"page":"987-996","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["GABAA receptor availability in clinical high-risk and first-episode psychosis: a [11C]Ro15-4513 positron emission tomography study"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-9102","authenticated-orcid":false,"given":"Paulina B.","family":"Lukow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia J.","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Severino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-3722","authenticated-orcid":false,"given":"Samuel R.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Kiemes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6582-2545","authenticated-orcid":false,"given":"Nicholas R.","family":"Livingston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"de Micheli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3582-6788","authenticated-orcid":false,"given":"Paolo","family":"Fusar-Poli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Haege","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Vorontsova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Donocik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenii A.","family":"Rabiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-5504","authenticated-orcid":false,"given":"Anthony A.","family":"Grace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-1941","authenticated-orcid":false,"given":"Steven C.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4381-0532","authenticated-orcid":false,"given":"Philip","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3562-0683","authenticated-orcid":false,"given":"Mattia","family":"Veronese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3766-3815","authenticated-orcid":false,"given":"Federico E.","family":"Turkheimer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-066X","authenticated-orcid":false,"given":"Gemma","family":"Modinos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"3204_CR1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S0006-3223(98)00138-3","volume":"44","author":"FM Benes","year":"1998","unstructured":"Benes FM, Kwok EW, Vincent SL, Todtenkopf MS. 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