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Imbalances in this evaluation are thought to characterize mood disorders such as major depressive disorder (MDD). We present a novel application of the drift diffusion model (DDM) suited to quantify how offers of reward and aversiveness, and neural correlates thereof, are dynamically integrated to form decisions, and how such processes are altered in MDD. Hierarchical parameter estimation from the DDM demonstrated that the MDD group differed in three distinct reward-related parameters driving approach-based decision making. First, MDD was associated with reduced reward sensitivity, measured as the impact of offered reward on evidence accumulation. Notably, this effect was replicated in a follow-up study. Second, the MDD group showed lower starting point bias towards approaching offers. Third, this starting point was influenced in opposite directions by Pavlovian effects and by nucleus accumbens activity across the groups: greater accumbens activity was related to approach bias in controls but avoid bias in MDD. Cross-validation revealed that the combination of these computational biomarkers were diagnostic of patient status, with accumbens influences being particularly diagnostic. Finally, within the MDD group, reward sensitivity and nucleus accumbens parameters were differentially related to symptoms of perceived stress and depression. Collectively, these findings establish the promise of computational psychiatry approaches to dissecting approach-avoidance decision dynamics relevant for affective disorders.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008955","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T19:07:23Z","timestamp":1620673643000},"page":"e1008955","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":60,"title":["Computational phenotyping of brain-behavior dynamics underlying approach-avoidance conflict in major depressive disorder"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-7783","authenticated-orcid":true,"given":"Mads L.","family":"Pedersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-1711","authenticated-orcid":true,"given":"Maria","family":"Ironside","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-6820","authenticated-orcid":true,"given":"Ken-ichi","family":"Amemori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie L.","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-7946","authenticated-orcid":true,"given":"Min S.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Graybiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Pizzagalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-0523","authenticated-orcid":true,"given":"Michael J.","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"pcbi.1008955.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cobeha.2017.12.002","article-title":"Economic choice: the foraging perspective.","volume":"24","author":"BY Hayden","year":"2018","journal-title":"Current Opinion in Behavioral Sciences"},{"key":"pcbi.1008955.ref002","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1023\/B:COTR.0000031809.20488.ee","article-title":"Approach and Avoidance Goals and Plans: Their Relationship to Anxiety and Depression.","volume":"28","author":"JM Dickson","year":"2004","journal-title":"Cognitive Ther Res."},{"key":"pcbi.1008955.ref003","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.psychres.2017.07.010","article-title":"Approach and avoidance tendencies in depression and anxiety disorders.","volume":"256","author":"SY Struijs","year":"2017","journal-title":"Psychiatry Research."},{"key":"pcbi.1008955.ref004","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.brat.2014.03.005","article-title":"An examination of avoidance in major depression in comparison to social anxiety disorder.","volume":"56","author":"ND Ottenbreit","year":"2014","journal-title":"Behav Res Ther"},{"key":"pcbi.1008955.ref005","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nn.4238","article-title":"Computational psychiatry as a bridge from neuroscience to clinical applications","volume":"19","author":"QJM Huys","year":"2016","journal-title":"Nat Neurosci"},{"key":"pcbi.1008955.ref006","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1177\/2167702614565359","article-title":"Model-Based Cognitive Neuroscience Approaches to Computational Psychiatry.","volume":"3","author":"TV Wiecki","year":"2014","journal-title":"Clin Psychological Sci"},{"key":"pcbi.1008955.ref007","doi-asserted-by":"crossref","first-page":"e0148409","DOI":"10.1371\/journal.pone.0148409","article-title":"A Computational Cognitive Biomarker for Early-Stage Huntington\u2019s Disease.","volume":"11","author":"TV Wiecki","year":"2016","journal-title":"Plos One."},{"key":"pcbi.1008955.ref008","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jmp.2010.01.004","article-title":"Using diffusion models to understand clinical disorders.","volume":"54","author":"CN White","year":"2010","journal-title":"J Math Psychol"},{"key":"pcbi.1008955.ref009","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1037\/0033-295X.85.2.59","article-title":"A theory of memory retrieval.","volume":"85","author":"R. 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