{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:47:13Z","timestamp":1793130433104,"version":"4.5.0"},"reference-count":64,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:sec id=\"ab-yoi250008-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern\u2013based biomarker for MDD that is linked to the underlying pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi250008-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine whether cortical ReHo patterns provide a replicable biomarker for MDD that is more sensitive than reduced cortical thickness and evaluate whether the ReHo MDD deficit pattern reflects regional cerebral blood flow (RCBF) deficit patterns in MDD and whether a regional vulnerability index (RVI) thus constructed may provide a concise brain pattern-based biomarker for MDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi250008-6\">\n                    <jats:title>Design, Settings, and Participants<\/jats:title>\n                    <jats:p>The UK Biobank (UKBB) participants had ReHo and structural measurements. Participants from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) Consortium were included for measuring the MDD structural cortical deficit pattern. The UKBB ReHo and ENIGMA cortical thickness effect sizes for MDD were used to test the deficit patterns in the Amish Connectome Project (ACP) with ReHo, structural, and RCBF data. Finally, the Ament Clinic Inc (ACI) sample had RCBF data measured using single-photon emission computed tomography. Data were analyzed from August 2021 to September 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi250008-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>ReHo and structural measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi250008-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Included in this analysis were 4 datasets: (1) UKBB (N\u2009=\u20094810 participants; 2220 with recurrent MDD and 2590 controls; mean [SD] age, 63.0 [7.5] years; 1121 female [50%]), (2) ENIGMA (N\u2009=\u200910\u202f115 participants; 2148 with MDD and 7957 healthy controls; mean [SD] age, 39.9 [10.0] years; 5927 female [59%]), (3) ACP (N\u2009=\u2009204 participants; 68 with a lifetime diagnosis of MDD and 136 controls; mean [SD] age,\u200941.0 [14.5] years; 104 female [51%]), and (4) ACI (N\u2009=\u2009372 participants; 296 with recurrent MDD and 76 controls; mean [SD] age, 45.3 [17.2] years; 189 female [51%]). MDD participants had lower cortical ReHo in the cingulum, superior temporal lobe, frontal lobe, and several other areas, with no significant differences in cortical thickness. The regional pattern of ReHo MDD effect sizes was significantly correlated with that of RCBF obtained from 2 independent datasets (Pearson\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.52 and Pearson\n                      <jats:italic>r<\/jats:italic>\n                      = 0.46;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). ReHo and RCBF functional RVIs showed numerically stronger effect sizes (Cohen\n                      <jats:italic>d<\/jats:italic>\n                      \u2009=\u20090.33-0.90) compared with structural RVIs (Cohen\n                      <jats:italic>d<\/jats:italic>\n                      \u2009=\u20090.09-0.20). Elevated ReHo-based RVI-MDD values in individuals with MDD were associated with higher depression symptom severity across cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi250008-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results of this case-control study suggest that the ReHo MDD deficit pattern reflected cortical hypoperfusion and was regionally specific in MDD. ReHo-based RVI may serve as a sensitive functional biomarker for MDD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.0192","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:54:11Z","timestamp":1743771251000},"page":"582","source":"Crossref","is-referenced-by-count":23,"title":["Functional vs Structural Cortical Deficit Pattern Biomarkers for Major Depressive Disorder"],"prefix":"10.1001","volume":"82","author":[{"given":"Peter","family":"Kochunov","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, UTHealth Houston School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhim M.","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, UTHealth Houston School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Keator","sequence":"additional","affiliation":[{"name":"Amen Clinics Inc, Costa Mesa, California"},{"name":"Department of Psychiatry and Human Behavior, University of California, Irvine,"},{"name":"Change Your Brain Change Your Life Foundation, Costa Mesa, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Amen","sequence":"additional","affiliation":[{"name":"Amen Clinics Inc, Costa Mesa, California"},{"name":"Change Your Brain Change Your Life Foundation, Costa Mesa, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, UTHealth Houston School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"Karcher","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrio","family":"Labate","sequence":"additional","affiliation":[{"name":"Departments of Mathematics, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Azencott","sequence":"additional","affiliation":[{"name":"Departments of Mathematics, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewen","family":"Huang","sequence":"additional","affiliation":[{"name":"Departments of Mathematics, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Syed","sequence":"additional","affiliation":[{"name":"Departments of Mathematics, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Maryland College Park, College Park"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny J. 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