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Biomedical subjects

R Hamish McAllister-Williams

Publications and source records attributed to R Hamish McAllister-Williams.

12 recordsLinked to original sources
PubMed2006

A study of the neural correlates of episodic memory and HPA axis status in drug-free depressed patients and healthy controls.

Altered laterality of cortical activity, neuropsychological impairment and hypercortisolaemia have been shown in depression. The neural correlates of episodic memory in healthy subjects demonstrate hemispheric laterality but it is not known whether this is affected by depression and/or hypercortisolaemia. Twenty-seven drug-free depressed patients and 29 matched healthy controls were studied. Event-related potentials (ERPs) were recorded during an episodic memory test. During the study phase, subjects heard words spoken in either a male or female voice. Old and new words were presented visually during a test phase, when subjects were requested to identify words as old or new and recollect the gender of the voice for old words. Cortisol levels were measured in saliva and plasma samples. The results showed a trend for elevated salivary cortisol concentration in depressed patients. Reaction times were significantly longer in patients; however, there was no difference in memory accuracy performance between the two groups. Recollection performance was found to be negatively correlated with age, with a similar trend for cortisol concentrations. ERP activity not specifically related to episodic memory retrieval recorded 200-500ms post-stimulus from controls showed a marked laterality, with higher voltages over the right hemisphere; however, was not seen in patients. There was significant correlation between cortisol and the laterality of the neural activity specifically related to episodic memory retrieval recorded 500-1400ms post-stimulus in both depressed and healthy groups. These unique findings demonstrate that while the laterality of the neural correlates of episodic memory is sensitive to cortisol, it is not altered by the non-specific laterality effects seen in depression.

Acoustic Stimulation↗
PubMed2006

Assessing cortisol and dehydroepiandrosterone (DHEA) in saliva: effects of collection method.

An increasing number of studies are utilizing saliva sampling as a method of assessing adrenal steroid secretion. Saliva samples have certain advantages over plasma, being non-invasive and easily collected. However, some methods of collection may compromise the accuracy of the assay, particularly those which employ aids to stimulate saliva production. We sought to compare the accuracy of cortisol and dehydroepiandrosterone (DHEA) measurement by examining the association between plasma levels, saliva and saliva collected using a citric acid-treated salivette device. Twenty six healthy male volunteers were recruited for the study. To increase the range of steroid levels in the samples collected, half the subjects were pre-treated with hydrocortisone (20mg, twice a day for 7 days) and half with placebo. Saliva samples were then collected from each subject using both a 'passive drool' method and a citric acid-treated salivette. A plasma sample was also collected. Cortisol and DHEA levels were measured by radioimmunoassay. For cortisol levels, both methods of saliva collection correlated highly with plasma levels and with each other (r 0.85; R(2) 0.72 for all). For DHEA levels, only saliva samples collected using the unstimulated collection method correlated with plasma levels. DHEA collected using the salivette device did not correlate significantly with either plasma or the unstimulated saliva (r 0.2;R(2) 0.04). It is crucial that future studies are aware of these issues and are cognizant of the effects of the method of collection when examining steroid levels in saliva.

Adolescent↗
PubMed2006

Relapse prevention in bipolar disorder: a critical review of current guidelines.

Bipolar disorder is an important and serious mental illness associated with significant morbidity and mortality. However, unfortunately, the evidence base regarding treatment is less than satisfactory. In such circumstances clinicians often resort to reputable sets of guidelines. A number of these currently exist; in the United Kingdom the most prominent being that produced by the British Association of Psychopharmacology (BAP). This paper reviews the methodology of this guideline and its recommendations regarding the long-term treatment of bipolar disorder and compares this with guidelines produced by the American Psychiatric Association (APA), the Canadian Network for Mood and Anxiety Treatments (CANMAT) and the Texas Implementation of Medication Algorithms (TIMA) for bipolar I disorder. It is concluded that the BAP guidelines continue to be a reasonable set of recommendations, though there are new data available since their publication. All the guidelines reviewed place lithium and valproate at the top of the list of options for long-term treatment. There is a trend to increasingly recognize atypical antipsychotics, particularly olanzapine, as an additional alternative and an increasing prominence of lamotrigine for prevention of depressive relapses. All other treatment options currently have an extremely limited evidence base and do not feature consistently in the published guidelines.

Algorithms↗
PubMed2005

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study.

RATIONALE: Dehydroepiandrosterone (DHEA) has been reported to enhance cognition in rodents, although there are inconsistent findings in humans. OBJECTIVES: The aim of this study was to investigate the effects of DHEA administration in healthy young men on episodic memory and its neural correlates utilising an event-related potential (ERP) technique. METHODS: Twenty-four healthy young men were treated with a 7-day course of oral DHEA (150 mg b.d.) or placebo in a double blind, random, crossover and balanced order design. Subjective mood and memory were measured using visual analogue scales (VASs). Cortisol concentrations were measured in saliva samples. ERPs were recorded during retrieval in an episodic memory test. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the cognitive task. RESULTS: DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory. Recollection accuracy in the episodic memory test was significantly improved following DHEA administration. LORETA revealed significant hippocampal activation associated with successful episodic memory retrieval following placebo. DHEA modified ERPs associated with retrieval and led to a trend towards an early differential activation of the anterior cingulate cortex (ACC). CONCLUSIONS: DHEA treatment improved memory recollection and mood and decreased trough cortisol levels. The effect of DHEA appears to be via neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing. These findings are distinctive, being the first to show such beneficial effects of DHEA on memory in healthy young men.

Adolescent↗
PubMed2003

Effects of acute tryptophan depletion on executive function in healthy male volunteers.

BACKGROUND: Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). METHODS: Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. RESULTS: Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. CONCLUSIONS: The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.

Adolescent↗
PubMed2002

Corticosterone modulation of somatodendritic 5-HT1A receptor function in mice.

Corticosteroid modulation of serotonergic function may play a central role in mood disorders. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produces a hypothermia in mice that serves as an in-vivo model of somatodendritic 5-HT1A autoreceptor function. Daily injections (s.c.) of 50 mg/kg of corticosterone (CORT) for 3 days attenuates 8-OH-DPAT hypothermia tested 24 h later. This study sought to further clarify the nature of the CORT-mediated attenuation of somatodendritic 5-HT1A receptor function. Mice underwent various CORT manipulations prior to an 8-OH-DPAT challenge. Neither 14-day bilateral adrenalectomy (ADX), nor CORT 50 mg/kg/day, administered continuously by osmotic minipump over 72 h had any effect on the 8-OH-DPAT hypothermic response. In contrast, daily injections of CORT over three consecutive days caused a significant attenuation in 8-OH-DPAT hypothermia when tested 24 h later. However, administration of an additional dose of CORT 2 h prior to the 8-OH-DPAT challenge occluded this CORT-mediated attenuation in a dose-dependent fashion. The findings demonstrate that CORT modulates somatodendritic 5-HT1A receptor function in a complex manner. Attenuation is seen only after intermittent administration of CORT. In addition, the degree of attenuation depends on CORT concentrations at the time of testing. These findings may have implications regarding mechanisms of adaptation to stress.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Rapid tranquillisation: time for a reappraisal of options for parenteral therapy.

BACKGROUND: When parenteral treatments are indicated for acutely disturbed behaviour, previous guidelines have recommended droperidol or haloperidol in combination with benzodiazepines. However, there has been recent concern over cardiotoxicity and sudden death associated with some antipsychotic medication and droperidol has now been withdrawn. AIMS: To ascertain what alternatives can be recommended to replace intramuscular droperidol. METHOD: Selective review of current guidelines and the literature pertaining to rapid parenteral tranquillisation. RESULTS: Current guidelines recommend haloperidol as an alternative to droperidol. There is evidence of cardiotoxicity with haloperidol and it has a propensity to cause extrapyramidal side-effects that may exacerbate disturbed behaviour and reduce longer-term compliance. The rapid-acting intramuscular formulations of atypical antipsychotic agents show promise. CONCLUSIONS: It is recommended that the mainstay of pharmacological rapid tranquillisation should be parenteral benzodiazepines used with due care.

Acute Disease↗