MRI measures of brain structure and function as predictors of medium-term response to psychotherapy in adolescent MDD

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Major depressive disorder (MDD) in adolescence is a challenging priority for NHS mental health services as well as being a difficult experience for the patient and their family. The recommended treatment is psychotherapy, which can be combined with antidepressants if there is no immediate response. Unfortunately, there is no way currently to predict which patients are most likely to respond to psychotherapy. This uncertainty stems in part from our incomplete knowledge of how depression is caused by abnormal function of brain circuits important for mood states and their conscious control. One plausible theory we want to investigate is that depressive symptoms result from an overactive response to negative events or stimuli in one part of the brain (the limbic system), which is not effectively controlled by an underactive response in a different but interconnected brain region (the frontal cortex). We predict that this functional imbalance in fronto-limbic brain networks can be normalised following cognitive behavioural therapy, a form of psychotherapy focused on improving conscious control of mood symptoms. We also expect that the extent of structural and functional abnormality measured in fronto-limbic brain networks before treatment begins can predict patients? responses to treatment up to one and a half years later.To test these predictions, we are proposing to collect magnetic resonance imaging (MRI) measurements of brain structure and function in 120 adolescent patients with MDD and 40 health adolescent volunteers. All of the patients will be scanned once before they are randomly assigned to one of three different kinds of psychological treatment as part of a larger study, already funded to investigate the clinical effectiveness of psychotherapy for young people with depression. Forty of the patients (and the healthy volunteers) will also be scanned on a second occasion 20 weeks later. MRI scanning is a painless and safe method of obtaining detailed information on the structure and function of the human brain. The design and clinical governance of this study has been informed by a careful consideration of the risks and benefits to adolescent patients and volunteers. We consider that it is timely and important to use modern brain scanning techniques to better understand and predict the course of this serious mental illness in young people and that this research proposal will safely and powerfully test key theoretical predictions in a way that could improve the future clinical care of adolescent patients with major depressive disorder.