fMRI studies of reward processing in adolescent depression.

Reward function is increasingly considered to be an important aspect of affective disorders such as depression and bipolar disorder. Conceptual models of affective disorders emphasize disrupted reward function as a neural characteristic of low positive affect in depression, and studies with adults have indicated that brain function in reward-related regions distinguishes those with depression from healthy controls. Based on an interest in adolescence, as both a vulnerable period for the onset of affective disorders and a period of ongoing development of neural reward circuitry, an emerging literature is now addressing reward-related brain function in adolescents with depression. Results have generally paralleled those from adult studies and have indicated value in studying reward function in relation to the etiology, pathophysiology, and treatment of depression in young people. Functional neuroimaging findings indicate that adolescents with depression (Forbes et al, 2009) and adolescents at risk for depression (eg, Gotlib et al, 2010) exhibit low striatal response to rewarding stimuli, such as money or happy facial expressions. This altered brain function has been observed during the anticipation of reward and the receipt of reward, suggesting that adolescent depression involves changes in both the motivation to obtain reward and the enjoyment of rewards once obtained. In addition, there is also some evidence that adolescents with depression exhibit more reactivity in prefrontal regions thought to have a role in regulating response to reward stimuli. Consistent with the findings of increased anterior cingulate response to reward in adults with depression, adolescents with depression exhibit less response in the medial prefrontal cortex (PFC) (Forbes et al, 2009), an area that is a key target, along with the striatum, of midbrain dopamine neurons. The medial PFC is a critical region in reward circuits, and its efferent connections include the ventral striatum (Haber and Knutson, 2010). The study of reward function has potential to elucidate many processes in the development and course of adolescent depression. Developmental findings that reward function changes with puberty and is associated with depressive symptoms in healthy adolescents (Forbes et al, 2010b) can inform the etiology of adolescent depression. Although the treatment implications of reward function research remain to be explored, initial findings suggest that adolescents' neural response to reward predicts symptom level and severity at outcome, as well as rate of symptom decrease during treatment for depression (Forbes et al, 2010a; Figure 1). This intriguing result represents one of the few biomarkers of antidepressant response in adolescent depression. Figure 1 In adolescents with major depressive disorder, (a) response to reward anticipation in the striatum (left) and medial prefrontal cortex (right) at treatment entry was related to (b) rate of reduction in anxiety symptoms during an 8-week treatment with ... Exciting new approaches to investigating reward function in adolescent depression include examining brain–behavior associations and employing personally relevant social stimuli. When combined with experience sampling, functional neuroimaging can identify regions of the striatum whose response distinguishes adolescents with depression from healthy adolescents and is also correlated with higher levels of positive affect experienced in natural environments (Forbes et al, 2009). Assessing neural response to social rewards, which are postulated to be critical for triggering adolescent depression (Davey et al, 2008), can provide a more meaningful understanding of altered reward function. In addition, future work will benefit from attention to clinical characteristics such as anhedonia, comorbid anxiety and clinical course.