Dataset Information

Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation.

ABSTRACT:

Importance

Nearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario.

Objectives

To establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation.

Design, setting, and participants

This longitudinal randomized observational prognostic study in a Swiss and German university setting collected data from July 1, 2015, to January 31, 2019, from 66 healthy controls and 123 patients in remission from major depressive disorder in response to antidepressants prior to and after discontinuation. Study recruitment took place until January 2018.

Exposure

Discontinuation of antidepressants.

Main outcomes and measures

Relapse during the 6 months after discontinuation. Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and the mechanisms identified through parameters of a computational model.

Results

A total of 123 patients (mean [SD] age, 34.5 [11.2] years; 94 women [76%]) and 66 healthy controls (mean [SD] age, 34.6 [11.0] years; 49 women [74%]) were recruited. In the main subsample, mean (SD) decision times were slower for patients (n?=?74) compared with controls (n?=?34) (1.77 [0.38] seconds vs 1.61 [0.37] seconds; Cohen d?=?0.52; P?=?.02), particularly for those who later relapsed after discontinuation of antidepressants (n?=?21) compared with those who did not relapse (n?=?39) (1.95 [0.40] seconds vs 1.67 [0.34] seconds; Cohen d?=?0.77; P?Conclusions and relevanceThis study found that the decision to invest effort was associated with prospective relapse risk after antidepressant discontinuation and may represent a persistent disease process in asymptomatic remitted major depressive disorder. Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation.

SUBMITTER: Berwian IM

PROVIDER: S-EPMC7042923 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation.

Berwian Isabel M IM Wenzel Julia G JG Collins Anne G E AGE Seifritz Erich E Stephan Klaas E KE Walter Henrik H Huys Quentin J M QJM

JAMA psychiatry 20200501 5

<h4>Importance</h4>Nearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario.<h4>Objectives</h4>To establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation.<h4>Design, setting, and participa ...[more]

PMID: 32074255

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Project description:The rat anterior cingulate cortex (ACC) mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., "courage"). As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm (HRA) but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the HRA. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain tasks.

Project description:ObjectivesTo explore associations between exposure to antidepressants, their discontinuation, depression [medicated or unmediated] and preterm birth [<37 and <32 weeks], small for gestational age (SGA) [<10th and <3rd centiles], breastfeeding [any] at 6-8 weeks.MethodsDesign: A population-based cohort study. Setting: The Secure Anonymised Information Linkage [SAIL] databank in Wales, linking maternal primary care data with infant outcomes. Participants: 107,573, 105,331, and 38,725 infants born 2000-2010 with information on prematurity, SGA and breastfeeding respectively, after exclusions. Exposures: Maternal antidepressant prescriptions in trimesters 2 or 3, discontinuation after trimester 1, recorded diagnosis of depression [medicated or unmediated] in pregnancy. Methods: Odds ratios for adverse pregnancy outcomes were calculated, adjusted for smoking, parity, socio-economic status, and depression.ResultsExclusive formula feeding at 6-8 weeks was associated with prescriptions in trimesters 2 or 3 for any antidepressants (adjusted odds ratio [aOR] 0.81, 95% confidence intervals 0.67-0.98), SSRIs [aOR 0.77, 0.62-0.95], particularly higher doses [aOR 0.45, 0.23-0.86], discontinuation of antidepressants or SSRIs after trimester 1 (aOR 0.70, 0.57-0.83 and 0.66, 0.51-0.87), diagnosis of depression aOR 0.76 [0.70-0.82), particularly if medicated (aOR 0.70, 0.58-0.85), rather than unmedicated (aOR 0.87, 0.82-0.92). Preterm birth at <37 and <32 weeks' gestation was associated with diagnosis of depression (aOR 1.27, 1.17-1.38, and 1.33, 1.09-1.62), particularly if medicated (aOR 1.56, 1.23-1.96, and 1.63, 0.94-2.84); birth at <37 weeks was associated with antidepressants, (aOR 1.24, 1.04-1.49]. SGA <3rd centile was associated with antidepressants (aOR 1.43, 1.07-1.90), and SSRIs (aOR 1.46, 1.06-2.00], particularly higher doses [aOR 2.10, 1.32-3.34]. All adverse outcomes were associated with socio-economic status and smoking.ImplicationsExposure to antidepressants or depression increased risks of exclusive formula feeding at 6-8 weeks, and prescription of antidepressants was associated with SGA <3rd centile. Prescription of antidepressants offers a useful marker to target additional support and additional care before and during pregnancy and lactation.

Dataset Information

Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation.

Importance

Objectives

Design, setting, and participants

Exposure

Main outcomes and measures

Results

Publications

Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation.

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