Explore the vast range of titles available.

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.

Apathy is a debilitating but poorly understood disorder characterized by a reduction in motivation. As well as being associated with several brain disorders, apathy is also prevalent in varying degrees in healthy people. Whilst many tools have been developed to assess levels of apathy in clinical disorders, surprisingly there are no measures of apathy suitable for healthy people. Moreover, although apathy is commonly comorbid with symptoms of depression, anhedonia and fatigue, how and why these symptoms are associated is unclear. Here we developed the Apathy-Motivation Index (AMI), a brief self-report index of apathy and motivation. Using exploratory factor analysis (in a sample of 505 people), and then confirmatory analysis (in a different set of 479 individuals), we identified subtypes of apathy in behavioural, social and emotional domains. Latent profile analyses showed four different profiles of apathy that were associated with varying levels of depression, anhedonia and fatigue. The AMI is a novel and reliable measure of individual differences in apathy and might provide a useful means of probing different mechanisms underlying sub-clinical lack of motivation in otherwise healthy individuals. Moreover, associations between apathy and comorbid states may be reflective of problems in different emotional, social and behavioural domains.

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.

Empathy - the capacity to understand and resonate with the experiences of other people - is considered an essential aspect of social cognition. However, although empathy is often thought to be automatic, recent theories have argued that there is a key role for motivation in modulating empathic experiences. Here we administered self-report measures of empathy and apathy-motivation to a large sample of healthy people (n = 378) to test whether people who are more empathic are also more motivated. We then sought to replicate our findings in an independent sample (n = 198) that also completed a behavioural task to measure state affective empathy and emotion recognition. Cognitive empathy was associated with higher levels of motivation generally across behavioural, social and emotional domains. In contrast, affective empathy was associated with lower levels of behavioural motivation, but higher levels of emotional motivation. Factor analyses showed that empathy and apathy are distinct constructs, but that affective empathy and emotional motivation are underpinned by the same latent factor. These results have potentially important clinical applications for disorders associated with reduced empathy and motivation as well as the understanding of these processes in healthy people.

Childhood-onset depression has adverse consequences that are sustained into adulthood, which increases the significance of detection in early childhood. The Children’s Depression Inventory (CDI) is used globally in evaluating depressive symptom severity in adolescents, and its second version, the CDI-2, was developed by taking into account advances in childhood depression research. Prior research has reported inconsistencies in its factor structure across populations. In addition, the CDI-2 has not yet been empirically validated with Southeast Asian populations. This study sought to empirically validate the CDI-2’s psychometric properties and evaluate its factorial structure with a Singaporean community sample of non-clinical respondents. A total sample of 730 Singaporean children aged between 8.5 and 10.5 years was used. Psychometric properties of the CDI-2, including internal consistency as well as convergent and discriminant validity, were assessed. Factor analyses were conducted to assess the developers’ original two-factor structure for a Southeast Asian population. This two-factor structure was not supported in our sample. Instead, the data provided the best fit for a hierarchical two-factor structure with factors namely, socio-emotional problems and cognitive-behavioural problems. This finding suggests that socio-cultural and demographic elements influence interpretation of depressive symptoms and therefore the emerging factor structure of the construct under scrutiny. This study highlights the need to further examine the CDI-2 and ensure that its interpretation is culture-specific. More qualitative work could also bring to light the idiosyncratic understanding of depressive symptomatology, which would then guide culture-specific validation of the CDI-2.

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.

Apathy is highly prevalent in Parkinson's disease. New findings suggest the syndrome is multifaceted. Here, we investigate whether all aspects of apathy are equally affected in Parkinson's disease and whether different dimensions of apathy were associated with depression and anhedonia. On the Apathy Motivation Index, while behavioral apathy and social apathy were elevated, emotional motivation was relatively preserved in Parkinson's disease, although a few patients did show impaired emotional sensitivity. Behavioral and social, but not emotional, apathy was associated with depression and anhedonia. These findings suggest aspects of motivation can be selectively impaired in Parkinson's disease and may have implications for guiding treatment.

Perseverative cognition (PC) is a transdiagnostic risk factor that characterizes both hypo-motivational (e.g., depression) and hyper-motivational (e.g., addiction) disorders; however, it has been almost exclusively studied within the context of the negative valence systems. The present study aimed to fill this gap by combining laboratory-based, computational and ecological assessments. Healthy individuals performed the Probabilistic Reward Task (PRT) before and after the induction of PC or a waiting period. Computational modeling was applied to dissociate the effects of PC on reward sensitivity and learning rate. Afterwards, participants underwent a one-week ecological momentary assessment of daily PC occurrence, as well as anticipatory and consummatory reward-related behavior. Induction of PC led to increased response bias on the PRT compared to waiting, likely due to an increase in learning rate but not in reward sensitivity, as suggested by computational modeling. In daily-life, PC increased the discrepancy between expected and obtained rewards (i.e., prediction error). Current converging experimental and ecological evidence suggests that PC is associated with abnormalities in the functionality of positive valence systems. Given the role of PC in the prediction, maintenance, and recurrence of psychopathology, it would be clinically valuable to extend research on this topic beyond the negative valence systems.

Purpose of review Major depressive disorder is a global public health concern that is common in adolescents. Targeting this illness at the early stages of development is critical and could lead to better long-term outcomes because the adolescent brain is highly plastic and, hence, neural systems are likely to be more malleable to interventions. Although a variety of treatments are available, there are currently no guidelines to inform clinicians which intervention might be most suitable for a given youth. Here, we discuss current knowledge of prognostic and prescriptive markers of treatment outcome in adolescent depression, highlight two major limitations of the extant literature, and suggest future directions for this important area of research. Recent findings Despite significant effort, none of the potential demographic (gender, age, race), environmental (parental depression, family functioning), and clinical (severity of depression, comorbid diagnoses, suicidality, hopelessness) predictors have been robustly replicated to warrant implementation in clinical care. Studies on biomarkers that truly reflect pathophysiology are scarce and difficult to draw conclusions from. Summary More efforts should be directed towards potential neurobiological predictors of treatment outcome. Moreover, rather than evaluating potential predictors in isolation, modern machine learning methods could be used to build models that combine information across a large array of features and predict treatment outcome for individual patients. These strategies hold promise for advancing personalized healthcare in adolescent depression, which remains a high clinical priority.