How do antidepressants influence the BOLD signal in the developing brain?

Depression is a highly prevalent life-threatening disorder, with its first onset commonly occurring during adolescence. Adolescent depression is increasingly being treated with antidepressants, such as fluoxetine. The use of medication during this sensitive period of physiological and cognitive brain development produces neurobiological changes, some of which may outlast the course of treatment. In this review, we look at how antidepressant treatment in adolescence is likely to alter neurovascular coupling and brain energy use and how these changes, in turn, affect our ability to identify neuronal activity changes between participant groups. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), the method most commonly used to record brain activity in humans, is an indirect measure of neuronal activity. This means that between-group comparisons - adolescent versus adult, depressed versus healthy, medicated versus non-medicated - rely upon a stable relationship existing between neuronal activity and the BOLD response across these groups. We use data from animal studies to detail the ways in which fluoxetine may alter this relationship, and explore how these alterations may influence the interpretation of BOLD signal differences between groups that have been treated with fluoxetine and those that have not.