Neural and neuroendocrine predictors of pharmacological treatment response in adolescents with depression: A preliminary study

Typically, about 30 to 50% of adolescents with depression fail to respond to evidence-based treatments, including antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). Efforts for identifying predictors and moderators of treatment response are needed to begin to address critical questions relevant to personalized care in adolescent depression. In this pilot study, we aim to identify biological predictors of response to antidepressant treatment. We used a multiple levels of analysis approach to evaluate threat system functioning (fronto-limbic system and the associated hormonal cascade) to determine if key biological indexes at baseline could predict improvement in depressive symptoms after eight weeks of antidepressant treatment in adolescents with depression. Neural predictors of favorable treatment response included lower amygdala connectivity with left supplementary motor area and with right precentral gyrus, and greater amygdala connectivity with right central opercular cortex and Heschl's gyrus connectivity during rest. During an emotion task, neural predictors of treatment response were greater activation of the bilateral anterior cingulate cortex and left medial frontal gyrus. Additionally, different patterns of salivary cortisol obtained in the context of a modified Trier Social Stress Test were associated with those whose depressive symptoms remitted as compared to those whose symptoms persisted. This approach shows significant promise for identifying predictors of treatment response in adolescents with depression. Future work is needed that incorporates sufficiently powered, randomized control trials to provide the basis by which both predictors and moderators of treatment response are identified. The hope is that this work will inform the development of methods that can guide clinician decision-making in assigning beneficial treatments for adolescents who are suffering from depression.