Reconsidering anhedonia in depression: Lessons from translational neuroscience

Abstract

Anhedonia is a core symptom of major depressive disorder (MDD), the neurobiological mechanisms of which remain poorly understood. Despite decades of speculation regarding the role of dopamine (DA) in anhedonic symptoms, empirical evidence has remained elusive, with frequent reports of contradictory findings. In the present review, we argue that this has resulted from an underspecified definition of anhedonia, which has failed to dissociate between consummatory and motivational aspects of reward behavior. Given substantial preclinical evidence that DA is involved primarily in motivational aspects of reward, we suggest that a refined definition of anhedonia that distinguishes between deficits in pleasure and motivation is essential for the purposes of identifying its neurobiological substrates. Moreover, bridging the gap between preclinical and clinical models of anhedonia may require moving away from the conceptualization of anhedonia as a steady-state, mood-like phenomena. Consequently, we introduce the term “decisional anhedonia” to address the influence of anhedonia on reward decision-making. These proposed modifications to the theoretical definition of anhedonia have implications for research, assessment and treatment of MDD.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…Other examples of DA agents effective in the treatment of MDD include the selective D 2 /D 3 receptor agonists pramipexole [292] and piribedil [293] the catechol-O-methyltransferase inhibitor tolcapone, [294], and the preferential presynaptic DA antagonist amisulpride, [295]. Particularly relevant in the present context are previous reports [290,296,297] that although both DA and non-DA agents can be used to effectively treat mood disorders, DA agents generally have superior effects on symptoms of anhedonia, specifically when compared with non-DA agents [19,298-300]. Tremblay and colleagues [226] reported that depressed patients had relatively greater increases in striatal and orbitofrontal cortex activation in response to emotional pictures after administration of dextroamphetamine (a stimulant associated with increased DA release).…”

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

“…Conversely, the approved pharmacotherapies for bipolar depression remain limited in number, often carry significant risks of metabolic side effects, and are not approved as monotherapy for major depression (Ghaemi et al, 2004;Connolly and Thase, 2011). Similarities of clinical presentation but the presence of differential risk of mania and treatment response suggests that bipolar and unipolar depression have both common and dissociable neurobiological substrates (Treadway and Zald, 2011;Chase et al, 2013). However, relatively little work has directly examined neurobiological phenotypes in both unipolar and bipolar depression (Chase et al, 2013).…”

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

“…Abnormalities in these dopaminergic and glutamatergic systems have been observed in numerous neuropsychiatric disorders, including Parkinson's disease (Griffith et al, 2008;Loane and Politis, 2011;Pavese et al, 2011), depression (Musazzi et al, 2012;Treadway and Zald, 2011), drug addiction (Martinez et al, 2009;Yang et al, 2009;Yucel et al, 2007), and schizophrenia (de la Fuente-Sandoval et al, 2013a,b;de la Fuente-Sandoval et al, 2011;Kegeles et al, 2010). The classical model of the basal ganglia developed in the 1980s (Obeso and Lanciego, 2011) predicts that loss of striatal dopamine will decrease extracellular levels of glutamate in the striatum and cortex (Albin et al, 1989(Albin et al, , 1995Jones, 2012).…”