Reward systems and cognitions in Major Depressive Disorder

Abstract

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.

[11C]raclopride positron emission tomography study of dopamine‐D2/3 receptor binding in patients with severe major depressive episodes before and after electroconvulsive therapy and compared to control subjects

“…14,53,54 Given the key role of dopamine in motivation and reward, and the cardinal symptom of anhedonia in major depression, a hyperdopaminergic tone in the striatum would seem unlikely. 55,56 Low D 2 /D 3 receptor density and thus reduced dopaminergic transmission would, however, be in line with the profoundly increased prevalence of MDE in patients suffering from Parkinson's disease, a known hypodopaminergic state. 52 Thus, the low raclopride binding demonstrated in the patients with MDE likely reflects low D 2 /D 3 receptor binding, although high striatal dopamine concentrations cannot be ruled out.…”

“…[ 11 C]raclopride binding has been shown to be sensitive to physiological changes in both D 2 /D 3 ‐receptor densities and in DA levels . Given the key role of dopamine in motivation and reward, and the cardinal symptom of anhedonia in major depression, a hyperdopaminergic tone in the striatum would seem unlikely . Low D 2 /D 3 receptor density and thus reduced dopaminergic transmission would, however, be in line with the profoundly increased prevalence of MDE in patients suffering from Parkinson's disease, a known hypodopaminergic state .…”

Personalized Psychiatry and Depression: The Role of Sociodemographic and Clinical Variables

“…71 Anhedonia is thought to reflect the dysfunction of the brain reward circuits, which are crucial for both the motivational drive and the ability to feel pleasure in response to events/activities (i.e., consummatory pleasure). [71][72][73] Findings from preclinical and clinical studies suggest the centrality of dopamine in motivational aspects of reward processing, while endogenous opioids may be involved in the hedonic experience. 74,75 More recently, other neurotransmitters, such as glutamate, have broadened the picture of mediation of reward and anhedonia at neurotransmitter level.…”

“…74,75 More recently, other neurotransmitters, such as glutamate, have broadened the picture of mediation of reward and anhedonia at neurotransmitter level. 73,76 From a clinical point of view, some studies point to relationships between anhedonia and severe behavioral and somatic MDD-related events. 58,77,78 For these reasons, it is of great importance when treating MDD to consider the therapeutic effectiveness of medications on this critical aspect of the disorder.…”

The Role of Tryptophan and Tyrosine in Executive Function and Reward Processing

“…Given that many depressive symptoms as defined by the DMS-5 could be described as impairments in reward processing (ie, a lack of motivation to obtain rewards; inability to experience pleasure; deficits in reinforcement learning), 45 it is perhaps not surprising that both 5-HT and DA would regulate its function. Deficits in the ability to predict and anticipate a reward (a core aspect of reinforcement learning), as seen in depressed patients, have been ascribed to dysfunction within the mesolimbic DA pathway.…”