Is depression associated with dysfunction of the central reward system?

Department of Psychiatry, University Hospital Zurich, Culmannstrasse 8, CH-8091 Zurich, Switzerland.
Biochemical Society Transactions (Impact Factor: 3.19). 03/2009; 37(Pt 1):313-7. DOI: 10.1042/BST0370313
Source: PubMed


The neural substrates of MDD (major depressive disorder) are complex and not yet fully understood. In the present review, I provide a short overview of the findings supporting the hypothesis of a dysfunctional dopamine system in the pathophysiology of depression. Because the mesocorticolimbic dopamine system is involved in reward processing, it has been hypothesized that a reduced function of this system could underlie the anhedonia and amotivation associated with depression. This hypothesis is supported by several observations providing indirect evidence for reduced central dopaminergic transmission in depression. However, some of the differences observed between controls and depressed patients in dopamine function seem to be specific to a subsample of patients, and influenced by the methods chosen. Studies that investigated the neural bases of some MDD behavioural symptoms showed that anhedonia, loss of motivation and the diminished ability to concentrate or make decisions could be associated with a blunted reaction to positive reinforcers and rewards on one side, and with a bias towards negative feedback on the other side. Only a few studies have investigated the neural basis of anhedonia and the responses to rewards in MDD subjects, mostly evidencing a blunted response to reward signals that was associated with reduced brain activation in regions associated with the brain reward system. In conclusion, there is evidence for a dysfunction of the dopamine system in depression and for blunted response to reward signals. However, the exact nature of this dysfunction is not yet clear and needs to be investigated in further studies.

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    North American Journal of Medical Sciences 08/2014; 6(8):370-6. DOI:10.4103/1947-2714.139283
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    • "Although 50% of the risk for major depressive disorder (MDD) is today considered genetic (Sullivan et al., 2000), identification of specific MDD-related genes has proved challenging. This is largely attributable to the multifactorial nature of the disease (American Psychiatric Association, 2000; Verhagen et al., 2008; Martin-Soelch, 2009) and methodological differences between studies (Lopez-Leon et al., 2008). One approach that is beneficial for identifying inheritable components of complex behavioral phenotypes is artificial selection in animal models, which allows controlled breeding along with replicable behavioral and molecular measurements (Finn et al., 2003; El Yacoubi and Vaugeois, 2007; Mackay, 2009). "
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    ABSTRACT: Major depressive disorder (MDD) is a common and devastating mental illness behaviorally characterized by various symptoms, including reduced motivation, anhedonia and psychomotor retardation. Although the etiology of MDD is still obscure, a genetic predisposition appears to play an important role. Here we used, for the first time, a multifactorial selective breeding procedure to generate a distinct 'depressed' rat line (DRL); our selection was based upon mobility in the forced swim test, sucrose preference and home-cage locomotion, three widely used tests associated with core characteristics of MDD. Other behavioral effects of the selection process, as well as changes in brain-derived neurotrophic factor (BDNF) and the response to three antidepressant treatments, were also examined. We show that decreased mobility in the forced swim test and decreased sucrose preference (two directly selected traits), as well as decreased exploration in the open field test (an indirectly selected trait), are hereditary components in DRL rats. In addition, lower BDNF levels are observed in the dorsal hippocampus of DRL rats, complying with the neurotrophic hypothesis of depression. Finally, electroconvulsive shocks (ECS) but not pharmacological treatment normalizes both the depressive-like behavioral impairments and the BDNF-related molecular alterations in DRL rats, highlighting the need for robust treatment when the disease is inherited and not necessarily triggered by salient chronic stress. We therefore provide a novel multifactorial genetic rat model for depression-related behaviors. The model can be used to further study the etiology of the disease and suggest molecular correlates and possible treatments for the disease.
    The International Journal of Neuropsychopharmacology 02/2014; 17(06):1-11. DOI:10.1017/S1461145714000030 · 4.01 Impact Factor
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    • "A second sensitivity analysis conducted on a subset of participants assessed with the PANSS confirmed the association of processing speed components with negative symptoms with the exception of AC. The lack of association between errors and negative symptoms may be due to the oversensitivity to negative feedback observed in negative affect (Cella, Dymond, & Cooper, 2010; Martin-Soelch, 2009). "
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    ABSTRACT: Introduction: Processing speed has been advanced as one of the core cognitive deficits of schizophrenia. Several methods were developed to assess this domain; however, most tasks, despite indexing several cognitive and motor components, tend to characterise processing speed as a unitary construct. This study explores potential subcomponents of processing speed in schizophrenia and their relationship with demographic, clinical, and neuropsychological characteristics. Methods: One hundred and sixty participants with a diagnosis of schizophrenia were assessed on neuropsychological tasks measuring processing speed, executive function, and memory. Demographics and clinical characteristics were also recorded. Three independent measures were extracted to account for subcomponents of processing speed: behavioural execution, response processing, and accuracy. Results: The identified components of processing speed were differently predicted by demographic characteristics, clinical characteristics, and overall intelligence estimates. Age and symptom severity were important predictors for behavioural execution; intelligence and social withdrawal predicted response processing; and accuracy was predicted by illness duration. Correlations showed executive function and memory to be associated with response processing and accuracy but not with behavioural execution. Conclusions: Distinct characteristics of schizophrenia seem to predict processing speed subcomponents. Distinguishing between behavioural, processing, and accuracy may be a useful way forward to refine our understanding of processing speed impairment in schizophrenia.
    Cognitive Neuropsychiatry 10/2012; 18(5). DOI:10.1080/13546805.2012.730038 · 1.91 Impact Factor
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