Reward-related decision-making in pediatric major depressive disorder: an fMRI study.

Affective neuroscience provides new ways of understanding the substrates of developmental psychopathology, including those associated with mood disorders. In depression, a likely substrate involves the neural systems implicated in reward processing (Nestler & Carlezon, 2006). Conceptual models from several perspectives postulate that depression is accompanied by altered motivation to obtain reward, low frequency of pursuing rewarding experiences, and reduced enjoyment of rewarding outcome (Forbes & Dahl, 2005). Functional brain imaging has investigated neural responses to rewarding events such as monetary wins (e.g., Delgado, Locke, Stenger, & Fiez, 2003) and simple feedback signals (Elliott, Sahakian, Michael, Paykel, & Dolan, 1998). Along with studies of non-human primates (Schultz, 2000), neuroimaging studies have revealed that reward processing occurs in regions including the dorsal and ventral striatum, amygdala, and orbitofrontal cortex (OFC). Functional abnormalities in all of these regions have been observed in depression (Drevets, 2001), although the specific nature of reward-processing disruptions in depression is still somewhat unclear. One reason may be that there are many sub-processes of reward responding, including decisions about possible future rewards and response to rewarding outcomes (Rogers et al., 2004). Decision-making itself involves several phases, each of which relies on the activity of specific brain regions (Ernst & Paulus, 2005). The striatum, amygdala, and OFC are among the brain regions implicated in processing a decision's outcome. In decision-making and anticipation of reward, relevant regions include the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, medial and lateral OFC, and ventral striatum (Ernst et al., 2004). Little is known about behavioral and neural responses to reward in child and adolescent depression. The only behavioral study of reward-related decisions to our knowledge reported that boys with current depressive disorders failed to distinguish low- and high-magnitude rewards under high-probability conditions (Forbes, Shaw, & Dahl, in press), and that reward-related decisions predicted depressive disorders and symptoms one year later. Neural response to reward processing has been studied in healthy young people (Bjork et al., 2004; Ernst et al., 2005; May et al., 2004) but not in those with affective disorders. Healthy adolescents exhibit neural responses that are generally similar to those in adults, but developmental effects have been reported, such as ventral but not dorsal activation in adolescents during a guessing task (May et al., 2004). During reward anticipation, adolescents exhibit ventral striatal activation (Bjork et al., 2004). During rewarding outcomes, adolescents exhibit activation of the amygdala (Ernst et al., 2005), ventral striatum (Ernst et al., 2005), lateral and medial OFC (May et al., 2004), and mesial prefrontal cortex (Bjork et al., 2004). Adults with depression fail to display increased ventral striatal activation to pleasant visual stimuli (Lawrence et al., 2004), and anhedonia is inversely correlated with amygdala and ventral striatal activation (Keedwell, Andrew, Williams, Brammer, & Phillips, 2005b). Extending this work by examining reward processing in pediatric depression can elucidate the affective mechanisms that are disrupted in the disorder, provide details on developmental effects, and suggest possible targets for both pharmacologic and psychosocial treatments of the disorder. The present study investigated how the neural correlates of reward-related decision-making in young people with Major Depressive Disorder (MDD) differ from those in typically developing control children. Using a functional magnetic resonance imaging (fMRI) reward paradigm, we attempted to examine group differences in two reward processes: decision-making/anticipation and outcome. Based on conceptual models and empirical findings, we hypothesized that MDD would be associated with (1) reduced neural response to reward decision-making/anticipation in the ACC, medial and lateral OFC, and striatum, and (2) reduced neural response to reward outcome in the striatum, amygdala, and OFC. We hypothesized, based on previous findings (Forbes, Shaw, & Dahl, in press), that participants with depression would exhibit less reward-seeking behavior than would participants in the control group. Secondarily, we examined the influence of anxiety disorders on neural response to reward. Analyses involving anxiety were exploratory because the anxiety-only group was small and because conceptual accounts provided little to guide our expectations. Anxiety disorders are thought to involve enhanced vigilance for threat (Mogg & Bradley, 1998; Vasey & Dadds, 2001), but some models propose that reward responding is not importantly disrupted in anxiety (Clark & Watson, 1991).