Accelerated aging of the putamen in patients with major depressive disorder

Abstract

IntroductionMajor depressive disorder (MDD) is primarily characterized by depressed mood and a blunted experience of pleasure (i.e., anhedonia). 1 The disorder is prevalent and chronic and represents a substantial personal, social and economic burden. [2][3][4] Neuroscience promises to elucidate mechanisms under lying depressive pathophysiology, leading to more effective approaches to the prevention and treatment of this debilitating disorder.Considerable evidence indicates that reward processing is dysfunctional in individuals with MDD. 5,6 The basal ganglia (BG) are a set of subcortical structures, including the striatum (caudate and putamen), nucleus accumbens and pallidum, that are critically involved in these reward processing steps. 7Previously research has indicated that depressed individuals have decreased activation in the striatum, 5,6 and some investigators have hypothesized that this abnormal activity affects decision-making. 5 Research in both animals and humans suggests that the dorsal striatum is involved in action selection and initiation and in encoding and integrating sensorimotor, cognitive and motivational/emotional information.8 Current evidence is mixed regarding specific roles of the putamen and caudate in reward processing. The results of several studies using fMRI suggest that whereas the putamen specifi cally encodes reward-related feedback, the caudate encodes both reward and punishment feedback.9,10 Finally, researchers have reported that the putamen is activated most strongly during anticipation of reward, whereas the caudate is activated most strongly during the receipt of reward. 8,10,11 A growing body of research indicates that adults with MDD have smaller volumes of the caudate 12-15 and putamen 13,14,16,17 than healthy controls. Postmortem studies have also reported smaller putamen volumes in depressed than in nondepressed adults. 18 It is important to note that these studies typically include adult samples with a mean age older than 40 years. Depression-associated differences in BG volumes are less consistent in samples of both younger adults 19,20 and adolescents. 21 It appears, therefore, that this discrepancy is associated with age differences in the study Background: Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants. Methods: We obtained whole-brain T 1 -weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests. Results: We included 232 individuals (116 patients with MDD) in our analy...

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

“…We speculate that depression may interact with the normal aging process, as results of diagnosis-by-age interaction analysis showed that MDD is associated with increased decline in overall and interhemispheric FA with age. These results suggest that MDD may be associated with accelerated brain aging, which has been shown for regional gray matter volume [44,45], although longitudinal studies are required to confirm this hypothesis. A previous study did not observe a diagnosisby-age interaction effect on WM, but this study was performed in a smaller sample of patients and controls and may have been underpowered to detect small effects [46].…”

Neurite atrophy in dorsal hippocampus of rat indicates incomplete recovery of chronic mild stress induced depression

“…The marked variation in ν and D L may be related to the reduced volume of the CP in the anhedonic group, an effect that is thought to be implicated in cognitive and motor abnormalities . In the same vein, clinical studies have also shown a significant reduction in the volume of CP in patients with depressive disorders . However, we did not observe any volumetric alterations in the CP either.…”

“…7 In the same vein, clinical studies have also shown a significant reduction in the volume of CP in patients with depressive disorders. 56 However, we did not observe any volumetric alterations in the CP either. Delgado y Palacios et al have reported a significantly higher volume of CP in a similar animal model of depression after eight weeks of CMS exposure.…”

Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

“…On one hand, the abnormal deposition of iron might be the result of the depression. Many fMRI studies have suggested that the basal nuclei displayed structural transformation as well as dysfunction in depression (Sacchet et al, 2017 ; Zhao et al, 2017 ). More and more evidence suggests that these changes to the basal nuclei, which are associated with motor function, and associative and limbic circuits, were related to the destruction of the dopaminergic system (Schroll and Hamker, 2016 ; Markett et al, 2017 ).…”