{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:19Z","timestamp":1792790299671,"version":"4.5.0"},"posted":{"date-parts":[[2026,4,29]]},"group-title":"Neuroscience","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Mental Health","award":["1R01MH110418-01A1"],"award-info":[{"award-number":["1R01MH110418-01A1"]}]},{"name":"National Institute of Biomedical Imaging and Bioengineering","award":["P41 EB017183"],"award-info":[{"award-number":["P41 EB017183"]}],"id":[{"id":"https:\/\/ror.org\/00372qc85","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Biomedical Imaging and Bioengineering","award":["U24 EB02898"],"award-info":[{"award-number":["U24 EB02898"]}],"id":[{"id":"https:\/\/ror.org\/00372qc85","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The NIMH Research Domain Criteria (RDoC) posits similar cellular pathologies for particular symptom domains across diagnostic categories. Conversely, knowledge that these differ could advance treatment discovery, especially for affective and non-affective psychoses, as studies usually intermix them.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We tested this by relating metabolite biomarker concentrations for cellular pathologies from whole hippocampal proton magnetic resonance spectroscopic imaging (\n                    <jats:sup>1<\/jats:sup>\n                    H MRSI) to symptom levels from the original and five factor PANSS, and the Hamilton Depression and Young Mania Scales. Biomarkers included: NAA (neuronal integrity); Cr (energy metabolism); Cho (membrane turnover); mI (glia); and Glx (glutaminergic neurotransmission). Participants were 26 healthy controls; 22 non-psychotic affective cases (NP-aff); and 33 with psychosis, including 20 schizophrenia (Scz) and 13 affective psychosis (aff-P) cases.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PANSS activation factor was related to reductions in all cellular component biomarkers in Scz, including glia (\u03c1=\u2212.84, p&lt;.001), membrane turnover (\u03c1=\u2212.45, p=.047), neural integrity (\u03c1=\u2212.54, p=.014), glutaminergic neurotransmission (\u03c1=\u2212.66, p=.037), and energy metabolism (\u03c1=\u2212.50, p=.024), but only to energy metabolism in NP-aff (\u03c1=\u2212.46, p=.030). Biomarkers for mood symptoms also varied across categories, suggesting gliosis for mania (\u03c1=.49, p=.025) and depression in HC (\u03c1=.55, p=.012), but increased membrane turnover for mania in aff-P (\u03c1=.65, p=.015), and decreased neural integrity (\u03c1=\u2212.45, p=.047)and energy metabolism (\u03c1=\u2212.45, p=.0496) for depression in Scz. In contrast, negative symptoms and autistic preoccupation were related to reduced glia in both NP-aff (\u03c1=\u2212.67, p=.005; \u03c1=\u2212.55, p=.029, respectively) and aff-P (\u03c1=\u2212.77, p=.042; \u03c1=\u2212.78, p=.040, respectively). Autistic preoccupation in Scz was related to both reduced glia (\u03c1=\u2212.55, p=.044)and membrane turnover (\u03c1=\u2212.45, p=.046). Only Scz showed a significant finding for positive symptoms; reduced membrane turnover (\u03c1=\u2212.52, p=.018).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>These results suggest both distinct and similar cellular pathologies for symptoms across diagnoses, including affective and non-affective psychoses. The differences support categorizing disorders and stratifying different psychoses in research rather than transdiagnostic approaches.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.27.721016","type":"posted-content","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:50:36Z","timestamp":1777452636000},"source":"Crossref","is-referenced-by-count":0,"title":["Do Symptom Domains Have Similar Cellular Underpinnings Across Psychiatric Diagnoses: Evidence from 3D Hippocampal MR Spectroscopy"],"prefix":"10.64898","author":[{"given":"Eugene","family":"Ruby","sequence":"first","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY 10027, USA"},{"name":"University of California, Los Angeles, Department of Psychology, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Gonen","sequence":"additional","affiliation":[{"name":"New York University Grossman School of Medicine, Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Lotan","sequence":"additional","affiliation":[{"name":"New York University Grossman School of Medicine, Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-6522","authenticated-orcid":false,"given":"Assaf","family":"Tal","sequence":"additional","affiliation":[{"name":"New York University Grossman School of Medicine, Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Rusinek","sequence":"additional","affiliation":[{"name":"New York University Grossman School of Medicine, Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose C","family":"Clemente Litran","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomics, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-8873","authenticated-orcid":false,"given":"Jessica","family":"Robinson-Papp","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, Departments of Neurology and Neuroscience, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine H.","family":"Karlsgodt","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles, Department of Psychology, Los Angeles, CA 90095, USA"},{"name":"University of California, Los Angeles, Department of Psychiatry, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Malaspina","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY 10027, USA"},{"name":"Icahn School of Medicine at Mount Sinai, Institute for Translational Research, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092519100537000_2026.04.27.721016v3.1","unstructured":"National Institutes of Mental Health. 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