A hallmark characteristic of Major Depressive Disorder (MDD) is the diminished experience of pleasure or reward. For example, compared with nondepressed persons, depressed individuals have been found to be characterized by attenuated reactivity to slides depicting pleasant scenes,1,2, 3
to amusing film clips,4
to pleasant drinks,5
and to monetary reward contingencies.6
Moreover, Pizzagalli et al.7
found that depressed individuals are impaired in their ability to integrate reinforcement history over time in a probabilistic reward task.
Recently, investigators have begun to examine neural aspects of responsivity to positive stimuli (see ). In unselected samples of participants, studies using functional imaging have found reward processing to be associated with increased activation in the striatum8–10
, insula, thalamus, and dorsal midbrain8,9,11,12
, and loss anticipation and outcomes to be associated with activation in the insula and the caudate13,14
, and with deactivation in the mesial frontal cortex8,9
. Regions such as the insula may play a role in both reward and loss processing by responding to uncertain reward and risk conditions. Moreover, faster learning of reward contingencies has been found to be associated with greater activation in dorsal anterior cingulate cortex (dACC), important for action and conflict monitoring, and in the basal ganglia15
. Although adolescents have generally been found to exhibit neural responses to reward stimuli similar to those found in adults16,17
, there are exceptions to this pattern. For example, Galvan et al.18
reported greater nucleus accumbens, relative to prefrontal, activity in adolescents than in children and adults during reward processing. In contrast, Eshel et al.19
found greater activation in the orbitofrontal cortex/VLPFC and dorsal ACC in adults than in adolescents when making risky monetary decisions. In a recent review, Casey et al.20
postulated that increased risk-taking behavior in adolescence is associated with a shift in activation of prefrontal regions from diffuse to more focal recruitment over time, and with elevated recruitment of subcortical regions.
Overview of neural patterns of activation and deactivation in response to reward and loss.
Researchers have begun to extend the investigation of neural aspects of reward processing to depressed adults and children. Knutson et al.21
examined patterns of neural activation in individuals diagnosed with MDD as they anticipated and received monetary reward and punishment. In contrast to never-depressed controls, who exhibited dACC activation during anticipation of loss, depressed participants were characterized by dACC activation during anticipation of reward, suggesting that they experience conflict when they anticipate receiving positive stimuli. Pizzagalli et al. 22
found that depressed adults had significantly less activation to rewarding outcomes in the left nucleus accumbens and bilateral caudate than did healthy controls, indicating dysfunction in the basal ganglia in MDD, particularly during the consummatory phase of reward processing. Kumar et al.23
found that, compared with healthy controls who received an acute dose of antidepressant medication, depressed adults receiving long-term antidepressant treatment exhibited significantly reduced activations in the ventral striatum, rostral and dorsal anterior cingulate, retrosplenial cortex, and midbrain and hippocampus. Steele et al.24
similarly reported that adults diagnosed with MDD exhibited less activation in the ACC in response to negative (lose) feedback and less activation in the ventral striatum in response to win feedback than did healthy controls.
In the first behavioral study of reward-related processing in boys with current depression, Forbes et al.25
reported that depression was associated with a reduced ability to distinguish between low- and high-magnitude rewards, which predicted depressive symptoms in a one-year follow-up assessment. In two subsequent studies, Forbes et al.26,27
found depression in children to be associated with reduced activation in reward-related brain areas during both anticipation of reward and reward outcome. Specifically, depressed children exhibited blunted responses in ACC, bilateral caudate, and OFC while both anticipating and receiving reward. Forbes et al.27
replicated their findings of reduced striatal responding in depressed children during reward anticipation and outcome, but also found greater activation in these participants in dorsolateral and medial prefrontal cortex.
It appears, therefore, that depressed adults and children are characterized by unique patterns of neural activity during the processing of reward stimuli. The role of this neural functioning in the course of depression, however, is not clear. It is possible, for example, that neural and/or behavioral anomalies in reward responsivity are present before the first onset of a depressive episode and represent a vulnerability factor that plays a role in the development of this disorder. Examining this possibility requires investigators to assess individuals before they experience their first episode of this disorder. In this context, it is well documented that approximately 40 percent of the offspring of depressed mothers will themselves develop depression.28–30
Thus, examining functional brain responses to the anticipation and receipt of reward and loss in children at high familial risk for depression who have not yet experienced a depressive episode themselves should help to identify patterns of neural activation that are involved in vulnerability to developing MDD.
To date, few investigators have examined reward processing in asymptomatic children who have a familial vulnerability for MDD prior to the onset of their first episode of depression. In a notable exception, Monk et al.31
found that children at familial risk for depression showed greater amygdala and nucleus accumbens activation while passively viewing fearful faces and lower nucleus accumbens activation while viewing happy faces. No studies, however, have examined reward processing in a sample of high-risk children who have not yet experienced any Axis I disorder. Investigating the neural bases of reward processing in such a sample would allow us to understand the nature of depression-associated difficulties in reward processing independent of current or past psychopathology. Because investigators have reported gender differences in the transmission and recurrence of depression in children27
, in the present study we examined neural functioning in carefully diagnosed, never-disordered daughters of mothers who have experienced recurrent episodes of MDD during their daughters’ lifetime and in age-matched control daughters of mothers with no past or current psychopathology. Drawing on findings obtained with depressed individuals21–27
, we predicted that, compared with daughters of never-disordered mothers, daughters of mothers with recurrent MDD would exhibit reduced activation in brain regions associated with reward-processing, including the striatum, insula, and ACC while anticipating and receiving gains. We predicted further that, while they anticipate and receive losses, daughters of mothers with recurrent MDD would show greater activation than would daughters of low-risk mothers in brain regions associated with conflict monitoring and harm avoidance, including the ACC and insula.