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Abstract
Major Depressive Disorder (MDD) is a debilitating and pervasive illness with a lifetime prevalence of between 10-15% of the world’s population. The prevailing hypothesis of depression is the stress neurotrophic hypothesis, and is characterised by excessive levels of stress and glucocorticoids. Excessive stress and glucocorticoids result in detrimental changes to the structure and functioning of the brain, including effects upon neuroplasticity. Neuroplasticity allows the brain to differentially respond to stimuli, and adapt to changes in the environment. Impaired neuroplasticity is linked to a number of symptoms in depression.
The thesis aims were to find a means to objectively test neuroplasticity in subjects suffering MDD, and to compare neuroplasticity with matched controls. A secondary aim was to discover if neuroplasticity changed with treatment for depression. To achieve these aims, three separate experiments were carried out.
The aim of the first study was to find a conditioning protocol that induced robust and consistent increases in motor cortical excitability, thus providing a means of measuring neuroplasticity, in healthy subjects. The selected conditioning protocol would be used for measurement of neuroplasticity in healthy and depressed populations in two subsequent studies.
Using the paired associative stimulation (PAS) protocol selected from study 1, the aim for study 2 was to compare neuroplasticity in depressed subjects with that of age and gender matched controls. By measuring motor cortical plasticity before and after PAS conditioning, this study provided one of the first objective demonstrations of impaired neuroplasticity in individuals with MDD that is not confounded by subject effort or motivation.
In study 3, PAS-induced neuroplasticity was measured twice in the same subjects. The first measure was taken while subjects were depressed, the second, after a treatment course of transcranial direct current stimulation. This study showed a significant improvement in neuroplasticity and mood state after treatment, though change in mood did not correlate with change in neuroplasticity.
This research supports a hypothesis of impaired neuroplasticity in depression. Thesis findings provide evidence of improved neuroplasticity and depressive symptoms after treatment, and thus provide important information about the pathophysiology and treatment of MDD.