The association between major depressive disorder and motivation to invest cognitive effort for rewards is unclear. One reason might be that prior tasks of cognitive effort-based decision-making are limited by potential confounds such as physical effort and temporal delay discounting.

To address these interpretive challenges, we developed a new task – the Cognitive Effort Motivation Task – to assess one's willingness to exert cognitive effort for rewards. Cognitive effort was manipulated by varying the number of items (1, 2, 3, 4, 5) kept in spatial working memory. Twenty-six depressed patients and 44 healthy controls went through an extensive learning session where they experienced each possible effort level 10 times. They were then asked to make a series of choices between performing a fixed low-effort-low-reward or variable higher-effort-higher-reward option during the task.

Both groups found the task more cognitively (but not physically) effortful when effort level increased, but they still achieved ⩾80% accuracy on each effort level during training and >95% overall accuracy during the actual task. Computational modelling revealed that a parabolic model best accounted for subjects' data, indicating that higher-effort levels had a greater impact on devaluing rewards than lower levels. These procedures also revealed that MDD patients discounted rewards more steeply by effort and were less willing to exert cognitive effort for rewards compared to healthy participants.

These findings provide empirical evidence to show, without confounds of other variables, that depressed patients have impaired cognitive effort motivation compared to the general population.

Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.

In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.

Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.

These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.