Abstract
Cognitive impairment is a functionally disabling feature of depression contributing to maladaptive decision-making, a loss of behavioral control and an increased disease burden. The ability to calculate the causal efficacy of ones actions in achieving specific goals is critical to normal decision-making and, in this study, we combined voxel-based morphometry (VBM), shape analysis and diffusion tensor tractography to investigate the relationship between cortical–basal ganglia structural integrity and such causal awareness in 43 young subjects with depression and 21 demographically similar healthy controls. Volumetric analysis determined a relationship between right pallidal size and sensitivity to the causal status of specific actions. More specifically, shape analysis identified dorsolateral surface vertices where an inward location was correlated with reduced levels of causal awareness. Probabilistic tractography revealed that affected parts of the pallidum were primarily connected with the striatum, dorsal thalamus and hippocampus. VBM did not reveal any whole-brain gray matter regions that correlated with causal awareness. We conclude that volumetric reduction within the indirect pathway involving the right dorsolateral pallidum is associated with reduced awareness of the causal efficacy of goal-directed actions in young depressed individuals. This causal awareness task allows for the identification of a functionally and biologically relevant subgroup to which more targeted cognitive interventions could be applied, potentially enhancing the long-term outcomes for these individuals.
Highlights
Depression is the leading cause of disability and morbidity in adolescence and young adulthood, with prevalence rates as high as 15% by the time a person reaches 25 years of age.[1,2] With its peak age of onset occurring between 15 and 29 years,[1] depression often occurs at a critical time for social, academic and occupational functioning and development.[3] low mood and anhedonia are core features of depression, cognitive dysfunction is another fundamental aspect of the disorder
Subsequent vertex-based shape analysis identified a localized correlation between reduced causal awareness and an inward position of surfaces on the right dorsolateral pallidum only, suggesting imbalance between the direct and indirect basal ganglia pathways
Probabilistic tractography revealed that these significantly correlated vertices were primarily connected with the striatum, dorsal thalamus and hippocampus
Summary
Depression is the leading cause of disability and morbidity in adolescence and young adulthood, with prevalence rates as high as 15% by the time a person reaches 25 years of age.[1,2] With its peak age of onset occurring between 15 and 29 years,[1] depression often occurs at a critical time for social, academic and occupational functioning and development.[3] low mood and anhedonia are core features of depression, cognitive dysfunction is another fundamental aspect of the disorder. Greater cognitive impairment is predictive of poorer academic, occupational and daily functioning independent of mood severity and is associated with higher rates of recurrent illness.[4] The cognitive symptoms of depression include deficits in working memory, learning and executive functioning,[5,6,7] which have been shown to persist even after mood symptoms resolve.[8] Importantly, aspects of executive function have long been recognized as depending on the accuracy of causal judgments and with regard to goal-directed action, on judgments concerning the causal efficacy of actions and their specific consequences.[9,10] This is true both of the ability to exert control over one's actions and to perceive the effects of actions on the environment, both of which have been thought deficient in depression,[10,11,12,13] and that, in the context of action control, are necessary for selecting appropriate actions and so for effective decision-making.[11] Previous studies have, provided mixed evidence as to whether people with depression experience deficits in causal awareness (for example, see Alloy and Abramson,[12] Eshel and Roiser[13] and Pizzagalli et al.14), likely due to heterogeneity in the measures employed and within the disorder itself.[15] Here we focused on action-related causal judgments in depression examining variations in the relationship between those judgments and the neural processes that support them. There is, evidence of reduced structural volumes within a cortical–striatal–pallidal–thalamic brain circuit, in structures critical for cortical regulation of the basal ganglia and in those that mediate feedback from the basal ganglia, the pallidum, to regulate cortical function.[23]
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