{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:01:16Z","timestamp":1790348476768,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011797","name":"Turun Yliopistollinen Keskussairaala","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005609","name":"Turun Yliopisto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022793","name":"Turun Yliopistos\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Parkinson's disease (PD) is associated with several behavioral and cognitive symptoms, the neurobiological background of which is not yet fully understood.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n The aim was to investigate the association between monoamine function and four specific nonmotor symptoms in early PD using the Parkinson's Progression Markers Initiative data.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n [\n 123<\/jats:sup>\n I]FP\u2010CIT SPECT imaging data of healthy controls (\n n<\/jats:italic>\n \u2009=\u2009166) and patients with PD at baseline (\n n<\/jats:italic>\n \u2009=\u2009349), 2\u2010year (\n n<\/jats:italic>\n \u2009=\u2009240), and 4\u2010year follow\u2010up (\n n<\/jats:italic>\n \u2009=\u2009140) were included. Depression, anxiety, rapid eye movement (REM) sleep behavior disorder (RBD) and cognition were evaluated using validated questionnaires. The associations between symptoms and subcortical monoamine transporter binding were analyzed voxel by voxel. Whole brain networks of symptom\u2010specific monoaminergic abnormalities were characterized using a functional connectome (\n n<\/jats:italic>\n \u2009=\u20091000) and normative neurotransmitter receptor maps.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cross\u2010sectionally, depression was associated with reduced ventral striatum (VS) binding at 2\u2010 and 4\u2010year and dorsal raphe (DRN) at 4\u2010year follow\u2010up (\n P<\/jats:italic>\n FWE<\/jats:sub>\n \u2009<\u20090.05); trait anxiety was associated with reduced DRN binding at 4\u2010year follow\u2010up (\n P<\/jats:italic>\n FWE<\/jats:sub>\n \u2009<\u20090.05). Longitudinally, lower baseline binding in these regions at baseline predicted more severe future depression and anxiety (\n P<\/jats:italic>\n FWE<\/jats:sub>\n \u2009<\u20090.05). RBD was most strongly linked to reduced VS binding at 2\u2010 and 4\u2010year follow\u2010up (nonsignificant after correction,\n P<\/jats:italic>\n FWE<\/jats:sub>\n \u2009<\u20090.1). Each of the symptom\u2010specific clusters was connected to distinct brain networks, corresponding to specific monoamine receptors: serotonin (5HT\n 1F<\/jats:sub>\n , 5HT\n 2A<\/jats:sub>\n , 5HT\n 5A<\/jats:sub>\n ) and histamine (H\n 3<\/jats:sub>\n ) for depression; histamine (H\n 1<\/jats:sub>\n ), serotonin (5HT\n 1E<\/jats:sub>\n , 5HT\n 1F<\/jats:sub>\n , 5HT\n 2A<\/jats:sub>\n , 5HT\n 3B<\/jats:sub>\n ), and adrenergic (\u03b1\n 1D<\/jats:sub>\n ) for anxiety; and adrenergic (\u03b2\n 2<\/jats:sub>\n ) and serotonin (5HT\n 1F<\/jats:sub>\n , 5HT\n 2C<\/jats:sub>\n , 5HT\n 5A<\/jats:sub>\n ) receptors for RBD.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The findings provide novel information about the monoaminergic networks underlying depression, anxiety, and RBD in PD. \u00a9 2026 The Author(s).\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70199","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:41:25Z","timestamp":1769841685000},"page":"1004-1015","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Monoaminergic Networks of Cognitive and Behavioral Symptoms in Early Parkinson's Disease"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-0815","authenticated-orcid":false,"given":"Kalle J.","family":"Niemi","sequence":"first","affiliation":[{"name":"Turku Brain and Mind Center University of Turku Turku Finland"},{"name":"Clinical Neurosciences University of Turku Turku Finland"},{"name":"Neurocenter Turku University Hospital Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-7093","authenticated-orcid":false,"given":"Valtteri","family":"Kaasinen","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University of Turku Turku Finland"},{"name":"Neurocenter Turku University Hospital Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-6325","authenticated-orcid":false,"given":"Rimona S.","family":"Weil","sequence":"additional","affiliation":[{"name":"UCL Dementia Research Centre, Institute of Neurology University College London London UK"},{"name":"National Hospital for Neurology & Neurosurgery University London Hospitals NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-9415","authenticated-orcid":false,"given":"Juho","family":"Joutsa","sequence":"additional","affiliation":[{"name":"Turku Brain and Mind Center University of Turku Turku Finland"},{"name":"Clinical Neurosciences University of Turku Turku Finland"},{"name":"Neurocenter Turku University Hospital Turku Finland"},{"name":"Turku PET Centre Turku University Hospital Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00330-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2018.08.008"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.3.308"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21596"},{"key":"e_1_2_11_7_1","article-title":"Antidepressants versus placebo for depression in primary care","volume":"3","author":"Arroll B","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.22854"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad338"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28722"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28404"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.03.001"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx348"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh445"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-130205"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.124.268233"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww162"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181feb2ab"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25103"},{"issue":"7","key":"e_1_2_11_20_1","first-page":"1129","article-title":"SPECT imaging of dopamine transporters in human brain with iodine\u2010123\u2010fluoroalkyl analogs of beta\u2010CIT","volume":"37","author":"Abi\u2010Dargham A","year":"1996","journal-title":"J Nucl Med"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199704)25:4<345::AID-SYN5>3.0.CO;2-A"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316193"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.03.025"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2016.10.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv215"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.108.051292"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210791293033"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.09.005"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29997"},{"key":"e_1_2_11_30_1","unstructured":"CohenA SoussandL McManusP FoxM.GSP1000 Preprocessed Connectome [Internet];2020. [cited 2023 Dec 7] Available from:https:\/\/dataverse.harvard.edu\/citation?persistentId=doi:10.7910\/DVN\/ILXIKS."},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25244"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01625-w"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1300\/J018v05n01_09"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26170"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8260.1983.tb00610.x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15890"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21740"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116189"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01834-y"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy161"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44220-022-00002-y"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11405"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.72129"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.01.011"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2013.0048"},{"key":"e_1_2_11_47_1","volume-title":"Python Tutorial","author":"Van Rossum G","year":"1995"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2003.10.002"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22212"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-202058"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.08.051"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19m12928"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.176"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01995-x"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.129"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26046"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27602"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13508"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-020-01777-2"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2020.02.001"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320157"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.02.010"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00802-5"},{"key":"e_1_2_11_64_1","first-page":"1","article-title":"Neuroanatomy and pathology of sporadic Parkinson's disease","volume":"201","author":"Braak H","year":"2009","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"e_1_2_11_65_1","article-title":"Antidepressants versus placebo for generalised anxiety disorder (GAD)","volume":"2","author":"Kopcalic K","year":"2025","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.2432"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.5582"},{"key":"e_1_2_11_68_1","article-title":"Hydroxyzine for generalised anxiety disorder","volume":"12","author":"Guaiana G","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70214-X"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00377-X"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-022-00409-5"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1706158"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405003111"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70199","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70199","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:19:50Z","timestamp":1790345990000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":72,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/mds.70199"],"URL":"https:\/\/doi.org\/10.1002\/mds.70199","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"2025-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}