{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:26:27Z","timestamp":1787203587804,"version":"build-2736575974"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Trace elements are pivotal to key biological processes, with possible effects on psychopathology. We investigated the hypothesis of shared genetic factors between trace elements levels, treatment resistance and related traits. We used genome\u2010wide summary statistics for trace elements blood concentration, treatment\u2010resistant depression (TRD), treatment\u2010resistant schizophrenia (TRS), and related traits, including anhedonia, neurovegetative symptoms, suicidal ideation, and cognition. Cross\u2010trait genetic correlations (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    ) were estimated with High\u2010Definition Likelihood with Bonferroni correction (\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2009=\u20090.0031). Significant\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    were tested by two\u2010sample Mendelian randomization (MR) and polygenic scores (PGSs) in UK Biobank. We found an inverse\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    between zinc and TRD (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    \u2009=\u2009\u22120.20, SE\u2009=\u20090.07,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20094.52\u2009\u00d7\u200910\n                    <jats:sup>\u22123<\/jats:sup>\n                    ), and a consistent non\u2010significant trend for TRS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.06). Copper correlated positively with appetite\/weight gain (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    \u2009=\u20090.11, SE\u2009=\u20090.036,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0026). MR provided no evidence of causal effects of zinc levels on TRD or copper levels on appetite\/weight gain, possibly reflecting weak instruments. The PGS of zinc was not associated with TRD, nor the PGS of copper with appetite\/weight gain, in UK Biobank (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915,927 and\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200935,849, respectively). Our results suggested genetic correlations involving zinc and TRD, copper and neurovegetative symptomatology, without support for a causal model or predictive effect of the respective PGSs. This may suggest limited power, residual confounding, or alternative shared genetic architectures.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.b.70030","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:01:42Z","timestamp":1787202102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trace Elements Genetics: A Potential Role in Treatment\u2010Resistant Major Psychoses and Related Traits?"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0276-7865","authenticated-orcid":false,"given":"Chiara","family":"Fabbri","sequence":"first","affiliation":[{"name":"Department of Biomedical and NeuroMotor Sciences University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-3759","authenticated-orcid":false,"given":"Alessandro","family":"Serretti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery Kore University of Enna  Enna Italy"},{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-539X","authenticated-orcid":false,"given":"Marco","family":"Menchetti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and NeuroMotor Sciences University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0748-4656","authenticated-orcid":false,"given":"Benedetta","family":"Vai","sequence":"additional","affiliation":[{"name":"Psychiatry and Clinical Psychobiology Unit IRCCS Ospedale San Raffaele  Milan Italy"},{"name":"University Vita\u2010Salute San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-856X","authenticated-orcid":false,"given":"Francesco","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Psychiatry and Clinical Psychobiology Unit IRCCS Ospedale San Raffaele  Milan Italy"},{"name":"University Vita\u2010Salute San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2004-5567","authenticated-orcid":false,"given":"Lidia","family":"Fortaner\u2010Uy\u00e0","sequence":"additional","affiliation":[{"name":"Psychiatry and Clinical Psychobiology Unit IRCCS Ospedale San Raffaele  Milan Italy"},{"name":"University Vita\u2010Salute San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9703-0083","authenticated-orcid":false,"given":"Concetta","family":"Crisafulli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmz084"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291724001880"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01802-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijpvm.IJPVM_478_20"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.02.042"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr050361j"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01674-3"},{"key":"e_1_2_11_9_1","first-page":"231","article-title":"Review: The Role of Zinc in the Endocrine System","volume":"32","author":"Baltaci A. 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