Brain imaging and lithium in bipolar disorder

Abstract

Bipolar disorder is a major mental illness affecting 1% of the world's population and whilst numerous treatments are available, lithium retains a key position in major treatment guidelines. Despite its widespread clinical use, the mechanism of action of lithium is unknown. This thesis uses magnetic resonance imaging techniques in order to expand our understanding of where and how lithium acts within the brain with regards to structural abnormalities that occur in bipolar disorder. The development of a novel imaging technique, 7Li-MRI, has enabled researchers to noninvasively measure lithium distribution in the brain. However, the stability of lithium distribution over time is unknown. We investigated the scan-rescan comparability of this technique and showed that whilst 7Li-MRI images exhibit high variability in terms of signal magnitude, the pattern of brain lithium distribution remains constant over one week. To investigate previous ndings which suggest an association between lithium use and increased white matter integrity we applied7Li-MRI alongside diffusion MRI to explore the spatial association between lithium distribution and white matter integrity in patients receiving treatment with lithium. Our ndings revealed a positive association between local lithium signal and white matter integrity, adding support to ndings which suggest that lithium exhibits a neuroprotective effect in white matter. Using a quantitative imaging technique we identied elevated longitudinal relaxation in the brains of patients with bipolar disorder relative to controls. The biological underpinnings and potential for this technique to serve as a diagnostic biomarker are discussed. In summary, using a range of magnetic resonance imaging acquisition techniques we have identied a number of structural brain differences between healthy subjects, lithium-treated patients and lithium-naïve patients.