Grant: Operating Grant

Discovering the neurobiological basis of major depression is one of the main challenges for today's society. Severe forms of depression affect 2-5% of the population, and rank among the top ten causes of disability. Magnetic resonance imaging (MRI) studies of patients with major depression have consistently shown a reduction in hippocampal volume relative to healthy subjects. Animal studies have also shown that antidepressant treatment can protect hippocampal structure and blocks the effects of stress. However, the information from most previous MRI studies in major depression has been inadequate to allow measurement of any such effects due to limited spatial resolution. The major advance in high field strength (4.7T) MRI by our research group has enabled a 5-fold improvement in the spatial resolution and quantification of specific cellular subfields of the hippocampus directly in depressed patients for the first time. The purposed study will investigate whether particular subfields of the hippocampus may be responsible for reductions in hippocampal volume in depression and to determine whether antidepressant treatment can reverse these changes. We will compare healthy adult controls with 2 groups of depressed patients: unmedicated depressed patients and patients on long term antidepressant treatment. All participants will undergo a high resolution MRI scan and the hippocampal subfields will be measured using a reliable protocol established by our group. In addition to MRI procedure, assessment of memory function and salivary cortisol will be conducted. A prospective follow up program for unmedicated patients will be initiated to repeat MRI scans after 16 weeks and after 12 months of continuous antidepressant treatment. The study will provide the first evidence of whether hippocampal structural plasticity in major depression is progressive and whether antidepressants are protective.