Lithium, magnetic resonance and the human brain

Abstract

This thesis explores the effects of lithium on the human brain using structural, functional and spectroscopic magnetic resonance techniques. Contemporary issues surrounding the pharmacological effects of lithium are investigated and aspects of its pharmacokinetics examined. Bipolar disorder is known to be associated with dysfunction of themonoaminergic neurotransmitter systems of the brain. It is proposed that the antimanic properties of lithium derive from its attenuation of the actions of dopamine. In a randomised, placebo-controlled study of lithium involving 24 healthymen, mania was modelled by the administration of methamphetamine. Sustained attention, known to be disturbed in mania, was assessed during functional magnetic resonance imaging. Within the lithium group, response times were slowed and the effects of methamphetamine on functional magnetic resonance imaging contrast diminished. These findings are discussed in the context of current theories and contrasted with existent data. Lithium has been reported to increase the volume of grey matter in the brain in numerous magnetic resonance imaging studies. This observation was replicated in a longitudinal, voxel-based morphometry study of 31 healthy men. Combining quantitative imaging with various structural analysis techniques, it is argued that the grey matter change may be better accounted for by lithium altering the relaxation characteristics of protons; that is to say, signal change not true volume expansion. The biophysical basis of this theory is discussed, together with its implications. The pharmacokinetic properties of lithium in man are incompletely characterised, in particular its distribution in various tissues of the brain. The development of a magnetic resonance spectroscopy tool is described; its purpose was to determine the concentration of lithium in grey and white matter in a time-scale suited to clinical practice. Lithium was found to be evenly distributed in the brain regions examined, with total acquisition times constrained to less than óþ minutes. The applications and future developments of in vivo lithium spectroscopy are considered. It is concluded that variousmagnetic resonance techniquesmay be usefully applied to the investigation of the interactions between lithium and the human brain.