Background Depression is common in HD, with major effects on quality of life. However, our knowledge of the most efficacious treatments and contributory cognitive mechanisms are limited. Aims Use the Enroll–HD periodic dataset to compare efficacy of major antidepressant classes in HD. Use a battery of cognitive tasks in a local cohort of x manifest HD patients to determine mechanisms contributing to depression in HD. Methods/Techniques Study 1) included any participant in ENROLL-HD started on an antidepressant for depression and recorded depression score at follow-up. Using the propensity scoring packages in R, we determined the probability of being assigned to different antidepressant classes based on known variables, and then included this in models of treatment outcome. Study 2) used established and novel tasks measuring a) effort for reward, b) reward value, c) reward learning and d) response to negative outcome to determine mechanisms leading to depression in HD. Results/Outcome Study 1) 5486 (37.71%) of participants received an antidepressant for depression. SSRIs and Bupropion had the highest probability of being free of depression at first follow-up and all subsequent follow-ups (32.70% and in 37.31%). Outcome models including the propensity score showed that SNRIs performed worse than SSRIs and Bupropion on both outcome measures. Study 2) We found deficits of effort for reward in HD participants compared with controls, and an association between depression score on the HADS and reduced effort for reward. We did not see an association of depression scores on the HADS and any other measure. Conclusions Antidepressants that are most effective in treating depression in HD differ from the most efficacious treatments for depression in the general population. A deficit in effort for reward is the major contributor to depression in HD. The most effective antidepressants in HD are also those with the largest effect on motivational anhedonia.
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