Neural representation of reward in recovered depressed patients

Abstract

Introduction Anhedonia, a loss of interest and pleasure in normally rewarding stimuli, is a key diagnostic criterion for major depression. It has been suggested that deficits in the processing of reward-relevant stimuli could represent an endophenotype for depression. We hypothesized that people at risk of depression by virtue of a personal history of the illness would show impaired neural responses to a primary rewarding stimulus. Materials and methods Using functional magnetic resonance imaging, we measured the neural response to the sight and flavor of chocolate, and their combination, in 13 unmedicated recovered patients with a history of major depression and 14 healthy controls matched for age and gender. We also examined a control aversive condition consisting of the sight of moldy strawberries and a corresponding unpleasant taste. Participants simultaneously recorded subjective ratings of "pleasantness," "intensity," and "wanting." Results and discussion Despite no differences between the groups in stimulus ratings, patients showed decreased neural responses to the pleasant stimulus in the ventral striatum and increases in the caudate nucleus to the aversive stimulus. Furthermore, patients had a diminished neural supralinearity response (the potentiation produced by simultaneous presentation of the sight and flavor of the stimuli) in the prefrontal cortex for both aversive and pleasant conditions. Patients recovered from depression appear to have deficits in the neural basis of reward and may also have impairments in the cross-modal integration of sensory stimuli. Conclusion These findings support the view that abnormal neural responses to reward may be an endophenotype for depression and a potential target for intervention and prevention strategies.

Not everyone's heart contracts to reward: Insensitivity to varying levels of reward in dysphoria

“…From a neuroscience perspective, there is evidence that clinically depressed, recovered depressed, and individuals at risk for depression show abnormal neural functioning during both reward anticipation and outcome phases (e.g., Forbes et al, 2009;Gotlib et al, 2010;Knutson et al, 2008;McCabe et al, 2009;Pizzagalli, Holmes, et al, 2009;Smoski et al, 2009;Steele et al, 2007). However, reward anticipation in relation with differences in incentive salience and dopamine functioning seems to be of particular importance (Berridge, 2007;Dichter, 2010;Nestler & Carlezon, 2006;Sherdell et al, 2011).…”

“…Finally, a number of recent studies demonstrated reduced activity in cortical and subcortical components of the neural reward circuit of depressed and dysphoric individuals, both during anticipation and outcome phases of reward processing (e.g., Forbes et al, 2009;Knutson et al, 2008;Pizzagalli, Holmes, et al, 2009;Smoski et al, 2009;Steele, Kumar, & Ebmeier, 2007). Most of these brain imaging studies concerned patients with major depression but also recovered depressed (McCabe, Cowen, & Harmer, 2009) and healthy populations at risk (Gotlib et al, 2010). In a similar vein, there is evidence for electrocortical hypoactivation of left prefrontal areas in depressed and dysphoric individuals-in the resting state but also during reward anticipation (e.g., Davidson, Pizzagalli, Nitschke, & Putnam, 2002;Gotlib, Ranganath, & Rosenfeld, 1998;Harmon-Jones et al, 2002;Shankman, Klein, Tenke, & Bruder, 2007;Thibodeau, Jorgensen, & Kim, 2006;Tomarken & Keener, 1998).…”

Blunted cardiovascular reactivity during social reward anticipation in subclinical depression

“…However, their role has not been fully understood. To date, a couple of studies have demonstrated associations between depression and reduced neural responses during the viewing of pleasant facial expressions and words (Epstein et al, 2006;Monk et al, 2008;Surguladze et al, 2005) and during the sight and taste of pleasant chocolate stimuli (McCabe et al, 2009;McCabe et al, 2012). These findings point to the general nature of reduced reward responsiveness in depression, beyond monetary rewards.…”

“…It is possible to conceive of a vicious cycle where impaired social reward responsiveness leads to even less social reinforcement from the environment and to even higher depression, and vice versa (Beck et al, 1979). Studies on remitted depressed patients and on high-risk populations suggest that reduced reward responsiveness might have trait-like character (Gotlib et al, 2010;McCabe et al, 2009;McCabe et al, 2012). Nevertheless, future studies using prospective longitudinal designs are needed to answer these questions.…”

Valence-Specific Effects ofBDNFVal66Met Polymorphism on Dopaminergic Stress and Reward Processing in Humans

“…In humans, mesolimbic activity and DA neurotransmission in the NAc are robustly engaged during the anticipation of a number of salient cues regardless of valence (Knutson et al, 2000;Scott et al, 2006;Scott et al, 2007b;McCabe et al, 2009;Spreckelmeyer et al, 2009). However, a potential role of BDNF on the processing of salient cues of different valences as it relates to DA neurotransmission has not been studied in humans.…”