{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:23:45Z","timestamp":1789795425148,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":111,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS125482"],"award-info":[{"award-number":["R01NS125482"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS124819"],"award-info":[{"award-number":["R01NS124819"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019211","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019211","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Depression in Parkinson\u2019s disease is often reported as being more debilitating than the motor symptoms and has been shown to accelerate disease progression. Identifying its underlying neurobiology is crucial in the discovery of mechanism-informed treatments. We hypothesize that lower synaptic density in mood circuitry drives symptoms of depression in Parkinson\u2019s disease. To test this hypothesis, we used PET imaging and [11C]UCB-J\u2014a radiotracer that binds to synaptic vesicle protein 2A (SV2A) to image synaptic density across patients with Parkinson\u2019s disease and depressive symptoms (PDd; n = 10), Parkinson\u2019s disease patients without depressive symptoms (PDnd; n = 20) and healthy controls (HCs; n = 18). The primary outcome was binding potential (BPND) in mood circuitry. Participants with PDd exhibited significantly lower synaptic density compared to HC and PDnd in the dorsolateral prefrontal cortex (dlPFC) (\u221222.0%, P &amp;lt; 0.001; \u221219.9%, P = 0.002), anterior cingulate cortex (ACC) (\u221227.9%, P &amp;lt; 0.001; \u221224.0%, P = 0.002), amygdala (\u221225.1%, P &amp;lt; 0.001; \u221218.9%, P = 0.006) and hippocampus (\u221228.1%, P &amp;lt; 0.001; \u221220.3%, P = 0.003). Synaptic density was significantly and negatively correlated with the severity of depressive symptoms across all participants with Parkinson\u2019s disease (n = 30) in the dlPFC (r = \u22120.59, P = 0.002), ACC (r = \u22120.68, P &amp;lt; 0.001), amygdala (r = \u22120.53, P = 0.004) and hippocampus (r = \u22120.56, P = 0.003). These findings provide the first in vivo evidence that lower synaptic density in mood-related brain regions may contribute to depression in Parkinson\u2019s disease. If confirmed, they would support the evaluation of interventions that target synaptic loss\/induce synaptic plasticity in individuals with Parkinson\u2019s disease and comorbid depression.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag136","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:33:30Z","timestamp":1776771210000},"source":"Crossref","is-referenced-by-count":3,"title":["Lower synaptic density in mood circuitry underlies depression in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"8","author":[{"given":"Salih","family":"Cayir","sequence":"first","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4408-2621","authenticated-orcid":false,"given":"Mika","family":"Naganawa","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Volpi","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranak","family":"Ebrahimian Sadabad","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dias","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, SUNY Downstate Health Science University , Brooklyn, NY 11203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Elliott","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3858-7563","authenticated-orcid":false,"given":"Amr","family":"Elshahat","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pittman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Esterlis","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]},{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]},{"name":"Department of Psychology, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabeel","family":"Nabulsi","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-8829","authenticated-orcid":false,"given":"Gerard","family":"Sanacora","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-5492","authenticated-orcid":false,"given":"Robert","family":"Comley","sequence":"additional","affiliation":[{"name":"Discovery Research Neuroscience , Abbvie, North Chicago, IL 60085 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd J","family":"Finnema","sequence":"additional","affiliation":[{"name":"Discovery Research Neuroscience , Abbvie, North Chicago, IL 60085 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E","family":"Carson","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sule","family":"Tinaz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Matuskey","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]},{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]},{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-1932","authenticated-orcid":false,"given":"Sophie E","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]},{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"issue":"2","key":"2026050811375227900_fcag136-B1","first-page":"183","article-title":"A systematic review of prevalence studies of depression in Parkinson's disease","volume":"23","author":"Reijnders","year":"2008","journal-title":"Mov 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