{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:49:23Z","timestamp":1776761363323,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,17]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01MH137331"],"award-info":[{"award-number":["R01MH137331"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R21MH138911"],"award-info":[{"award-number":["R21MH138911"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Depression is associated with risk for late-onset Alzheimer\u2019s disease (LOAD), but its underlying pathogenesis in at-risk individuals remains unclear. We examined multimodal imaging correlates of depressive symptoms in cognitively normal middle-aged offspring of patients with LOAD (O-LOAD) compared with control individuals without LOAD history up to a 4\n                    <jats:sup>th<\/jats:sup>\n                    degree of kinship (HC).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants (n=58; 52\u00b13 years; 74% female) underwent assessment with the Beck Depression Inventory-II (BDI), structural MRI, resting-state fMRI, FDG-PET, and PiB-PET. Resting-state fMRI data were available for 28 O-LOAD and 24 HC; PET data for 24 O-LOAD and 22 HC. General linear models tested associations between imaging measures and BDI, including group interactions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In O-LOAD, higher BDI scores were associated with reduced cortical thickness in the left postcentral gyrus. Resting-state fMRI revealed significant group-by-BDI interactions involving cingulate and orbitofrontal networks. In O-LOAD, greater depressive symptom severity was associated with reduced cingulate connectivity across distributed corticolimbic, prefrontal, insular, occipital, and cerebellar regions (\u03b2 range \u22120.10 to \u22120.18). In HC, depressive symptoms were associated with reduced right orbitofrontal and somatosensory\u2013medial orbitofrontal connectivity (\u03b2=\u22120.13), with divergent patterns of cingulate connectivity. FDG-PET showed no significant associations with depressive symptoms. PiB-PET demonstrated regionally specific associations between amyloid signal and BDI in HC, involving an inverse pattern in anterior and posterior insular cortices.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Depressive symptoms in middle-aged individuals at familial risk for LOAD are associated with distinct structural and functional alterations, involving circuitry subserving salience and reward, and suggesting early network-level mechanisms linking affective symptoms with vulnerability to neurodegeneration.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.13.717731","type":"posted-content","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:35:17Z","timestamp":1776443717000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinct Multimodal Imaging Correlates of Depression in Middle-Aged Adults With and Without a Family History of Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"given":"Barbara","family":"Duarte-Abritta","sequence":"first","affiliation":[{"name":"Laboratory of Chronophysiology, Institute for Biomedical Research (BIOMED), Pontifical Catholic University of Argentina (UCA) and CONICET, Buenos Aires, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Abulafia","sequence":"additional","affiliation":[{"name":"Laboratory of Chronophysiology, Institute for Biomedical Research (BIOMED), Pontifical Catholic University of Argentina (UCA) and CONICET, Buenos Aires, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Lucha contra las Enfermedades Neurol\u00f3gicas de la Infancia (FLENI), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Tafet","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Naresh K. Vashisht College of Medicine, Texas A&M University, College Station, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Ignacio","family":"Brusco","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Argentina"},{"name":"Department of Psychiatry and Mental Health, University of Buenos Aires School of Medicine, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Tsuchiyagaito","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay J.","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Naresh K. 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