{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:14:11Z","timestamp":1790741651539,"version":"4.1.0"},"reference-count":201,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Welsh Clinical Academic Track fellowship"},{"name":"Welsh Assembly Government"},{"name":"Ser Cymru II fellowship"},{"name":"European Regional Development Funds"},{"name":"Wellcome ISSF fellowship","award":["513688"],"award-info":[{"award-number":["513688"]}]},{"name":"Medical Research Council"},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"crossref","award":["602245"],"award-info":[{"award-number":["602245"]}],"id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Depression is more common in neurodegenerative diseases such as Huntington\u2019s disease than the general population. Antidepressant efficacy is well-established for depression within the general population: a recent meta-analysis showed serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants and mirtazapine outperformed other antidepressants. Despite the severe morbidity, antidepressant choice in Huntington\u2019s disease is based on Class IV evidence. We used complementary approaches to determine treatment choice for depression in Huntington\u2019s disease: propensity score analyses of antidepressant treatment outcome using the ENROLL-HD data set, and a dissection of the cognitive mechanisms underlying depression in Huntington\u2019s disease using a cognitive battery based on the Research Domain Criteria for Depression. Study 1 included ENROLL-HD 5486 gene-positive adult patients started on an antidepressant medication for depression. Our outcome measures were depression (Hospital Anxiety and Depression Scale or Problem Behaviours Assessment \u2018Depressed Mood\u2019 item) at first follow-up (primary outcome) and all follow-ups (secondary outcome). The intervention was antidepressant class. We used Svyglm&amp;Twang in R to perform propensity scoring, using known variables (disease progression, medical comorbidity, psychiatric morbidity, sedatives, number of antidepressants, demographics and antidepressant contraindications) to determine the probability of receiving different antidepressants (propensity score) and then included the propensity score in a model of treatment efficacy. Study 2 recruited 51 gene-positive adult patients and 26 controls from the South Wales Huntington\u2019s Disease Management Service. Participants completed a motor assessment, in addition to measures of depression and apathy, followed by tasks measuring consummatory anhedonia, motivational anhedonia, learning from reward and punishment and reaction to negative outcome. We used generalised linear models to determine the association between task performance and depression scores. Study 1 showed selective serotonin reuptake inhibitors outperformed serotonin norepinephrine reuptake inhibitors on the primary outcome (P = 0.048), whilst both selective serotonin reuptake inhibitors (P = 0.00069) and bupropion (P = 0.0045) were superior to serotonin norepinephrine reuptake inhibitors on the secondary outcome. Study 2 demonstrated an association between depression score and effort for reward that was not explained by apathy. No other mechanisms were associated with depression score. We found that selective serotonin reuptake inhibitors and bupropion outperform serotonin norepinephrine reuptake inhibitors at alleviating depression in Huntington\u2019s disease. Moreover, motivational anhedonia appears the most significant mechanism underlying depression in Huntington\u2019s disease. Bupropion is improves motivational anhedonia and has a synergistic effect with selective serotonin reuptake inhibitors. This work provides the first large-scale, objective evidence to determine treatment choice for depression in Huntington\u2019s disease, and provides a model for determining antidepressant efficacy in other neurodegenerative diseases.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac278","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T21:00:26Z","timestamp":1667941226000},"source":"Crossref","is-referenced-by-count":22,"title":["Different depression: motivational anhedonia governs antidepressant efficacy in Huntington\u2019s disease"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5356-5019","authenticated-orcid":false,"given":"Duncan James","family":"McLauchlan","sequence":"first","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, Cardiff University , Cardiff CF24 4HQ , UK"},{"name":"Department of Neurology, Morriston Hospital, Swansea Bay University Health Board , Swansea SA6 6NL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1322-2449","authenticated-orcid":false,"given":"Thomas","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, Cardiff University , Cardiff CF24 4HQ , UK"},{"name":"Cardiff University Brain Research Imaging Center, Cardiff University , Cardiff CF24 4HQ , UK"},{"name":"Department of Psychology, University of Bath , Bath BA2 7AY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Craufurd","sequence":"additional","affiliation":[{"name":"Manchester Center for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Center , Manchester M13 9PL , UK"},{"name":"St. Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Center , Manchester M13 9WL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E J","family":"Linden","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, Cardiff University , Cardiff CF24 4HQ , UK"},{"name":"Cardiff University Brain Research Imaging Center, Cardiff University , Cardiff CF24 4HQ , UK"},{"name":"Department of Psychology, University of Bath , Bath BA2 7AY , UK"},{"name":"School for Mental Health and Neuroscience, Fac. Health, Medicine and Life Sciences, Maastricht University , Maastricht , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-4753","authenticated-orcid":false,"given":"Anne E","family":"Rosser","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, Cardiff University , Cardiff CF24 4HQ , UK"},{"name":"Department of Neurology, Morriston Hospital, Swansea Bay University Health Board , Swansea SA6 6NL , UK"},{"name":"School of Biosciences, Cardiff University , Cardiff CF10 3AX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"issue":"2","key":"2023062214151610400_fcac278-B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/mds.21803","article-title":"A systematic review of prevalence studies of depression in Parkinson\u2019s 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