Academic journal article Cognitive, Affective and Behavioral Neuroscience

Reward-Related Brain Function as a Predictor of Treatment Response in Adolescents with Major Depressive Disorder

Academic journal article Cognitive, Affective and Behavioral Neuroscience

Reward-Related Brain Function as a Predictor of Treatment Response in Adolescents with Major Depressive Disorder

Article excerpt

The present study provides preliminary evidence that pretreatment reward-related brain function in the striatum and medial prefrontal cortex (PFC) could have relevance for predicting both final level and rate of change of clinical characteristics in adolescents with major depressive disorder. Adolescents with depression underwent a functional MRI scan during a monetary reward task, participated in an 8-week open trial of cognitive behavioral therapy (CBT) or CBT plus selective serotonin reuptake inhibitor, and completed reports of anxiety and depressive symptoms before, during, and after treatment. Clinicians rated adolescents' improvement and severity at the same time points. Growth models were used to examine change in clinical characteristics and its association with brain function. Severity, anxiety symptoms, and depressive symptoms decreased over treatment. Final levels of severity and anxiety symptoms were associated with pretreatment striatal reactivity, and rate of anxiety symptom reduction was associated with greater striatal reactivity and lower medial PFC reactivity.

Research on the etiology, pathophysiology, and clinical course of depression can contribute to the development of new treatments and the refinement of existing treatments. Importantly, because variability exists both in response to empirically supported treatments for depression and in affect-related brain function among people with depression, there is the potential to determine whether individual differences in affect-related brain function are associated with response to treatment. Thus, research on the neural substrates of depression can possibly reduce the heterogeneity of treatment response and contribute to the goal of improving outcomes by personalizing treatment.

Because depression is considered to be a disorder of affect regulation (Forbes & Dahl, 2005; Gross & Muñoz, 1995), neural response to affective stimuli could indicate alterations in many processes relevant to treatment response, including subjective experience of affect-eliciting events, ability to engage interpersonally in psychosocial treatment, and functioning of neural circuits potentially influenced by psychosocial or pharmacologic treatments. Studies have begun to address affect-related brain function as a predictor of treatment response, with stimuli including sad faces (Costafreda, Khanna, Mourao-Miranda, & Fu, 2009; Fu et al., 2008), fearful faces (Salvadore et al., 2009), happy faces (Fu et al., 2007), positive and negative affective words (Siegle, Carter, & Thase, 2006), and positive and negative affective faces (Sheline et al., 2001; Whalen et al., 2008). These studies have addressed improvement with cognitive behavioral therapy (CBT; e.g., Fu et al., 2008) and pharmacotherapy (e.g., Salvadore et al., 2009), focusing on both depression (e.g., Siegle et al., 2006) and anxiety disorders (e.g., Whalen et al., 2008).

Adolescence is a particularly important point in the life span for understanding the implications of brain function for treatment response, since intervention early in the clinical course of depression-and during brain development-could be especially helpful in preventing future episodes. Adolescence is a time of great increase in the incidence of depression (Angold, 1988; Lewinsohn, Clarke, Seeley, & Rohde, 1994), and many adults with depression experienced their first episode during adolescence (Lewinsohn, Rohde, Klein, & Seeley, 1999; Weissman et al., 1999).

Reward-related brain function could be a particularly fruitful target for investigating affect-related brain function as a predictor of treatment response in adolescent depression. Reduced reward-related striatal function has been observed in adolescents and adults with depression (Epstein et al., 2006; Forbes, Hariri, et al., 2009; Keedwell, Andrew, Williams, Brammer, & Phillips, 2005; Surguladze et al., 2005), and it is postulated to be associated with affective and motivational features of the disorder (Davey, Yücel, & Allen, 2008; Forbes & Dahl, 2005). …

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