Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study

Abstract

Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the nucleus accumbens, within the mesolimbic pathway. Although dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown whether alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in 27 participants including healthy volunteers and psychiatric patients with schizophrenia, depression, or cocaine addiction, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) multimodal imaging with a voxel-based statistical approach. Dopamine transporter (DAT) availability was assessed with PET and [C]PE2I as a marker of presynaptic dopamine function, and reward-related neural response was assessed using fMRI with a modified Monetary Incentive Delay task. Across all the participants, DAT availability in the midbrain correlated positively with the neural response to anticipation of reward in the nucleus accumbens. Moreover, this relationship was conserved in each clinical subgroup, despite the heterogeneity of mental illnesses examined. For the first time, a direct link between DAT availability and reward anticipation was detected within the mesolimbic pathway in healthy and psychiatric participants, and suggests that dopaminergic dysfunction is a common mechanism underlying the alterations of reward processing observed in patients across diagnostic categories. The findings support the use of a dimensional approach in psychiatry, as promoted by the Research Domain Criteria project to identify neurobiological signatures of core dysfunctions underling mental illnesses.

Increased responses of the reward circuitry to positive task feedback following acute stress in healthy controls but not in siblings of schizophrenia patients

“…More specifically, studies in rodents that used optogenetic stimulation of dopaminergic VTA neurons have shown both increased striatal activity (Ferenczi et al, 2015;Lohani et al, 2017) and no effect on striatal activity (Brocka et al, 2018) and therefore it remains unknown whether dopaminergic activity plays a causal role in striatal activity. In support of a link between DA functioning and striatal neurovascular response, human studies found a correlation between reward-induced striatal activity as measured with fMRI and reward-induced DA release (Schott et al, 2008) or dopamine transporter availability (Dubol et al, 2018) as measured with PET. In conclusion, these results suggests that DA functioning plays a role in striatal responses to rewards and that alterations in the DA system in siblings may underlie altered reward responses following stress.…”

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits

“…Together with subsequent dysfunction in dopaminergic and glutamatergic signaling, increased inflammation may lead to motivational deficits and negative symptoms in patient with schizophrenia. schizophrenia and major depression has been the positive relationship between dopamine transporter availability and the fMRI BOLD response in the nucleus accumbens to reward anticipation has been described in both disorders (123). Individuals at clinical high-risk for schizophrenia from the North American Prodrome Longitudinal Study (NAPLS) cohort have depressive symptoms that have been shown to be associated with negative symptoms (124).…”

The Nucleus Accumbens: A Common Target in the Comorbidity of Depression and Addiction

“…The DA system in the NAc is also involved in emotion-related behaviors, particularly behaviors related to depression (Luscher and Malenka, 2011 ; Lammel et al, 2014 ; Li et al, 2019 ). Dopaminergic dysfunction is a common mechanism in a variety of reward and motivational disorders, including addiction and depression (Dubol et al, 2018 ).…”