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Research Interests |
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Research Interests I am a member of the Psychobiology Research Group in the School of Neurology, Neurobiology and Psychiatry. This group is comprised of clinical and pre-clinical scientists with an interest in the biology of mood disorders, stress and addiction. My own interests particularly relate to the role of the hypothalamic – pituitary – adrenal (HPA) axis and the serotonergic system in cognition and the pathophysiology and treatment of mood disorders. I have a particular interest in the use of electroencephalographic techniques for exploring brain function following cognitive and pharmacological challenges. My research into serotonergic-HPA axis interactions has shown in animals that while repeated pulses of high doses of corticosteroids attenuate somatodendritic 5-HT1A receptor function [21], continuous administration and lowering corticosteroid levels by adrenalectomy have no effect [13]. I am also involved in parallel neuroendocrine studies in healthy volunteers that have shown that an acute dose of corticosterone attenuates postsynaptic 5-HT1A receptor responses, an effect seen with hydrocortisone [7], but not dexamethasone [8]. I have written major reviews that include a novel model of the interaction of the serotonergic system and the HPA axis and its role in depression [9, 10], and relate these systems to neuropsychological function and consciousness [19]. While an MRC Clinican Scientist Fellow I developed EEG methods of examining 5-HT1A receptor function in man, something hither to impossible. These techniques involve the administration of (relatively) selective probes to subjects and monitoring their effect on the serontonergic system using novel computational methods of examining the EEG [18]. These methods are now being utilised to study the effects of corticosteroids on somatodendritic 5-HT1A receptor function in man as well as examining the functional integrety of these receptors in depressed patients. An additional component of my current research portfolio is an investigation of the effects of corticosteroids and 5-HT on neuropsychological function based on hypotheses raised in a previous review [9]. The effects of chronic administration of corticosteroids on episodic memory have been examined in healthy volunteers utilising a word recollection event related potential (ERP) technique. This work was done in collaboration with Professor Mick Rugg of the Institute of Cognitive Neuroscience, University College London. This study demonstrated that cortisol has distinct effects on neural activity that occurs during an episodic memory task [16]. These investigations have been extended demonstrating that unlike repeated administration, an acute dose of cortisol does not impair episodic memory, but it does alter the neural correlates of error processing [22]. Acutely lowering tryptophan also impairs both episodic memory [20] and executive function [23], but interestingly does not alter a putative method of assessing serotonergic function in man [24]. Most recently we have demonstrated that the corticosteroid functional antagonist, DHEA, leads to an improvement in mood and episodic memory in young healthy men [25]. This is a finding we are hoping to follow up in clinical populations. I have obtained several research grants including from the MRC, The Wellcome Trust, The Nuffield Foundation and industry. Copyright Hamish McAllister-Williams © 2006. |