{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:15:35Z","timestamp":1787508935528,"version":"build-2736575974"},"reference-count":36,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":92,"URL":"https:\/\/www.cambridge.org\/core\/terms"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institute on Aging, National Institutes of Health"},{"name":"German Federal Ministry of Education and Research"}],"content-domain":{"domain":["europsy-journal.com","clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Eur. psychiatr."],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S092493380000643X_abst0005\" sec-type=\"other\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Metabolic syndrome and impaired insulin sensitivity may occur as side effects of atypical antipsychotic drugs. However, studies of\n                      <jats:italic>peripheral<\/jats:italic>\n                      insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) or oral glucose tolerance tests (OGTT) suggest that abnormal glucose metabolism is already present in drug-naive first-episode schizophrenia (DNFES). We hypothesized impairments of\n                      <jats:italic>neuronal<\/jats:italic>\n                      insulin signaling in DNFES.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S092493380000643X_abst0010\" sec-type=\"methods\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      To gain insight into neuronal insulin-signaling\n                      <jats:italic>in vivo<\/jats:italic>\n                      , we analyzed peripheral blood extracellular vesicles enriched for neuronal origin (nEVs). Phosphorylated insulin signal transduction serine-threonine kinases pS312-IRS-1, pY-IRS-1, pS473-AKT, pS9-GSK3\u03b2, pS2448-mTOR, pT389-p70S6K and respective total protein levels were determined in plasma nEVs from 48 DNFES patients and healthy matched controls after overnight fasting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S092493380000643X_abst0015\" sec-type=\"results\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Upstream pS312-IRS-1 was reduced at trend level (p = 0.071; this condition may amplify IRS-1 signaling). Exploratory omnibus analysis of downstream serine-threonine kinases (AKT, GSK3\u03b2, mTOR, p70S6K) revealed lower phosphorylated\/total protein ratios in DNFES vs. controls (p = 0.013), confirming decreased pathway activation. Post-hoc-tests indicated in particular a reduced phosphorylation ratio of mTOR (p = 0.027). Phosphorylation ratios of p70S6K (p = 0.029), GSK3\u03b2 (p = 0.039), and at trend level AKT (p = 0.061), showed diagnosis-dependent statistical interactions with insulin blood levels. The phosphorylation ratio of AKT correlated inversely with PANSS-G and PANSS-total scores, and other ratios showed similar trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S092493380000643X_abst0020\" sec-type=\"conclusions\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings support the hypothesis of neuronal insulin resistance in DNFES, small sample sizes notwithstanding. The counterintuitive trend towards reduced pS312-IRS-1 in DNFES may result from adaptive feedback mechanisms. The observed changes in insulin signaling could be clinically meaningful as suggested by their association with higher PANSS scores.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.eurpsy.2019.08.012","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T17:18:53Z","timestamp":1570209533000},"page":"124-129","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"title":["Insulin-signaling abnormalities in drug-na\u00efve first-episode schizophrenia: Transduction protein analyses in extracellular vesicles of putative neuronal 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