{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:45:32Z","timestamp":1790376332349,"version":"4.1.0"},"reference-count":54,"publisher":"Cambridge University Press (CUP)","issue":"13","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0033291719002277_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and <jats:italic>\u03b3<\/jats:italic>-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).<\/jats:p><\/jats:sec><jats:sec id=\"S0033291719002277_sec_a2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>Thirty-nine antipsychotic-na\u00efve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (\/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA\/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291719002277_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Before treatment, thalamic glutamate\/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate\/Cr and GABA\/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate\/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA\/Cr in ACC. Baseline levels in responders and HCs did not differ.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291719002277_sec_a4\" sec-type=\"conclusions\"><jats:title>Conclusion<\/jats:title><jats:p>Glutamatergic and GABAergic abnormalities in antipsychotic-na\u00efve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291719002277","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T11:21:56Z","timestamp":1568632916000},"page":"2182-2193","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":71,"title":["Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-na\u00efve patients with psychosis"],"prefix":"10.1017","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-3154","authenticated-orcid":false,"given":"Kirsten B.","family":"Bojesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn H.","family":"Ebdrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper","family":"Jessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Sigvard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Tangmose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.E.","family":"Edden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik B.W.","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egill","family":"Rostrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian V.","family":"Broberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte Y.","family":"Glenth\u00f8j","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"S0033291719002277_ref53","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20548"},{"key":"S0033291719002277_ref1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210984110"},{"key":"S0033291719002277_ref3","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.110.079608"},{"key":"S0033291719002277_ref50","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbu220"},{"key":"S0033291719002277_ref19","first-page":"218","volume-title":"Clinical Global Impressions ECDEU Assessment Manual for Psychopharmacology, Revised (DHEW Publ. 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