The current study’s findings are consistent with hypotheses of altered reward processing and reduced positive affect in young people with major depressive disorder (2
). During the anticipation and receipt of monetary rewards, young people with diagnosed major depressive disorder exhibited reduced response in dorsal striatal reward areas. Activation in caudate regions in which the major depressive disorder group showed reduced response relative to the comparison group was positively correlated with subjective positive affect that participants experienced during a weekend in their natural settings. Within the major depressive disorder group, the combination of reward processing, sex, and age accounted for a considerable amount of variance in real-world positive affect. Thus, disruption of reward processing in adolescents with major depressive disorder in the context of a simple fMRI task appears to be predictive of their real-world affective experience.
Decreased striatal response in young people with major depressive disorder could indicate depression-related difficulties with several aspects of reward processing. Disruption of response in the caudate, for example, could suggest difficulties with the execution of action in response to rewarding cues (12
). The caudate receives input from ventral tegmental dopamine neurons, and unusual function in young people with depression supports claims that depression involves disrupted dopamine signaling (3
). Whether such disruption represents a state-like response during a depressive episode or a stable, trait-like difference in reward processing—and whether it changes with development or clinical course—must be addressed by longitudinal, prospective studies.
In addition to exhibiting reduced responding in reward-related brain areas, the major depressive disorder group exhibited greater responding than comparison subjects in prefrontal cortical areas postulated to play a role in affect regulation (Brodmann’s area 9) and social cognition (Brodmann’s area 10) (22
). Based on models of frontostriatal connectivity and the integrative function of dopamine systems (23
), greater activation in these regions in combination with less activation in reward-related areas may reflect overregulation of reward responding in young people with major depressive disorder. Perhaps when waiting for or obtaining a reward, young people with depression diminish the onset or maintenance of their response by engaging cognitive and regulatory circuits.
The presence of enhanced activation in medial Brodmann’s area 10 in the major depressive disorder group during rewarding outcomes is consistent with findings that depressed adults exhibit increased activation in this area during affective contexts intended to induce pleasant mood (10
). In combination with the putative self-referential and social cognitive functions of medial Brodmann’s area 10 (22
), this finding suggests that young people with depression might think about themselves or their status in relation to others (e.g., “everyone’s winning more than I am”) rather than enjoying a pleasant outcome. Given that medial prefrontal cortex is also active during so-called default states thought to involve self-reflection (25
), another interpretation of this finding is that adolescents with depression find it difficult to disengage from their ongoing, baseline cognitive activity in the presence of reward.
Although sample size limited our power to detect some effects within developmental groups, analyses within the pre/early and mid/late adolescent groups revealed that youths with major depressive disorder in both developmental groups exhibited reduced striatal reactivity relative to comparison subjects. Thus, alterations to reward-related brain function in depression might occur in both children and adolescents. Of importance, the pattern we observed in the major depressive disorder group stands in contrast to developmental evidence that healthy adolescents exhibit enhanced striatal activation when responding to reward (26
). This difference from healthy adolescents raises questions about the consequences of disruptions to reward-related brain function during a developmental period in which this function is undergoing change. Therefore, it will be valuable for future studies to examine the separate and interacting influences of depression and development on reward processing in adolescents, as well as the importance of altered reward processing for long-term clinical course.
Our findings differ in some respects from those of other studies of reward-related brain function in depression. For example, others have reported decreased orbitofrontal reactivity in response to reward in young people with depression (6
) or a negative relation between amygdala reactivity and anhedonia (28
). While our hypotheses focused more on striatal reactivity, we found some orbitofrontal reactivity within the major depressive disorder group but no differences between the major depressive disorder and comparison groups in reactivity of the orbitofrontal cortex or amygdala. A possible reason for this discrepancy is that our reward task is similar to those that reliably engage striatal reward areas (11
) and does not include other types of affective stimuli such as human faces.
Similarly, sample size and composition limited our ability to test whether depression-related differences were present within male and female subsamples. Girls were overrepresented in our sample, but gender was unlikely to serve as a confound because both the major depressive disorder and comparison groups had greater proportions of girls than boys. Anxiety symptoms, higher in the major depressive disorder group than the comparison group, were another possible confound. Although results did not change when we adjusted for anxiety symptoms, it is possible that the presence of anxiety influenced our results, especially since we found previously that anxiety symptoms appear to contribute uniquely to reward processing in young people (6
). Our paradigm was a straightforward monetary reward task that allowed us to examine one class of natural rewards but precluded us from considering other aspects of reward, such as social context, subjective experience, and varying magnitude. We did not obtain mood ratings during the reward task, and unfortunately we were thus unable to test the hypothesis that group differences in brain function reflect differences in subjective experience of reward.
In sum, this study indicates that young people with depression appear to exhibit unusual patterns of neural response to two components of reward processing. Neural response was further related to subjective affect in natural settings, providing validation for the use of laboratory-based reward paradigms to measure aspects of positive affect. A greater understanding of the affective factors in depression will ideally lead not only to increased knowledge of the pathophysiology of depression but also to treatments that target the affective systems disrupted by the experience of this disorder.