Lack of effect of tryptophan depletion on the loudness dependency of auditory event related potentials in healthy volunteers.

It has previously been suggested that auditory event related potentials (AEPs) are a potential marker of central serotonergic (5-HT) activity in man, with the slope of the AEP amplitude stimulus intensity function (ASF-slope) inversely correlating with 5-HT activity. However, two recent studies investigating this hypothesis in healthy subjects by rapidly lowering central 5-HT concentrations using the acute tryptophan depletion paradigm have found no effect on ASF-slope [Biological Psychology, 59 (2002) 121; Psychopharmacology (Berl), 146 (1999) 101]. These studies employed a 50g tryptophan depletion drink, which has been argued may not lower central 5-HT concentrations sufficiently. We here report the effect of tryptophan depletion on the AEP ASF-slope using 100g amino acid drinks with and without tryptophan in 14 healthy male subjects, employing a within subject, double blind, random, balanced order, cross-over design. No significant effect of tryptophan depletion was found on ASF-slope. These negative findings cast further doubt on the hypothesis that the ASF-slope is an indicator of central 5-HT function.

Effects of a single dose of cortisol on the neural correlates of episodic memory and error processing in healthy volunteers.

RATIONALE: Neuropsychological impairments seen in depression may be secondary to hypercortisolaemia. Repeated cortisol administration impairs episodic memory with an alteration in event-related potentials (ERPs) recorded during information retrieval. It is unclear whether such ERP effects are specific to episodic memory, or whether repeated cortisol administration is required. OBJECTIVE: To investigate the effect of a single dose of hydrocortisone on the neural correlates of episodic memory and error detection. METHODS: Twenty healthy subjects were treated with hydrocortisone (100 mg) or placebo orally, in a double-blind, two-way crossover study. ERPs were recorded during an episodic memory and a Stroop task, 1-3 h following the medication. RESULTS: Cortisol increased error rates during the Stroop task but had no effect on episodic memory. The magnitude of ERPs associated with incorrect response in the Stroop task between -250 ms and +500 ms post-response was increased by cortisol, with no effect on correct-response ERPs. There was no effect of cortisol on episodic memory-retrieval-dependent ERPs. CONCLUSIONS: Cortisol can impair not only episodic memory but also processes involved in error detection. In contrast to repeated cortisol administration, a single dose of cortisol does not alter the behavioural performance or the electrophysiological correlates of episodic memory. However, it increases error rates in a choice response task with associated quantitative changes in incorrect-response ERPs. This probably reflects an alteration in anterior cingulate cortex activity. Such changes may contribute to the neuropsychological impairment seen in depression. This study also demonstrates the utility of ERPs for investigating the effect of neuroendocrine manipulations on the neural correlates of neuropsychological function.

EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans.

RATIONALE: An involvement of 5-HT(1A) receptors is postulated in the pathophysiology of affective disorders and mechanism of action of antidepressants. Methods for studying their functional integrity in humans are, however, limited. Preliminary data suggests that activation of somatodendritic 5-HT(1A) receptors cause a negative shift in the EEG frequency spectrum. Animal research suggests that pindolol is an agonist at these receptors but an antagonist at postsynaptic 5-HT(1A) receptors. OBJECTIVE: We postulated that while pindolol would antagonise known postsynaptic mediated neuroendocrine responses to the 5-HT(1A) agonist buspirone, both drugs would have a similar effect on the EEG frequency spectrum. METHODS: Fourteen healthy men were administered placebo or pindolol (20 mg orally) 90 min before placebo or buspirone (30 mg orally) in a double blind cross-over study. Plasma prolactin and growth hormone were assayed and EEGs recorded before and after drug administration. RESULTS: A significant negative shift in the EEG frequency spectrum was found for both buspirone and pindolol, with the combination producing a similar effect to each drug alone. In contrast, the neuroendocrine response to buspirone was significantly attenuated by pindolol. CONCLUSIONS: The data obtained are consistent with the EEG effects of buspirone and pindolol being mediated by somatodendritic 5-HT(1A) receptors, in contrast to the neuroendocrine response, which is known to be mediated by postsynaptic receptors. The development of this novel method of assessing somatodendritic 5-HT(1A) receptors in humans is a potentially important advance which may allow the testing of hypotheses of its involvement in depression and response to antidepressants.

Effects of tryptophan depletion on brain potential correlates of episodic memory retrieval.

RATIONALE: Neuropsychological impairments in depressive illness may be secondary to proposed serotonergic abnormalities. Acute tryptophan depletion (ATD) in healthy subjects impairs episodic memory, but the mechanism of this is unclear. OBJECTIVES: To examine the effects of ATD on the neural correlates of episodic memory retrieval in healthy subjects. METHODS: Fourteen healthy men were given an amino acid cocktail drink with or without tryptophan, in a double blind, crossover design. Event related potentials (ERPs) were recorded during a well-validated episodic memory task performed 5 h after drink ingestion. Subjects listened to words spoken in a male or female voice. At test, old and new words were presented visually; subjects judged whether words were old or new, and if old, the gender of the voice at study. RESULTS: ATD led to an 84+/-5% reduction in plasma free tryptophan concentrations, and significantly impaired episodic memory recall. ERP recordings demonstrated previously reported left parietal and right frontal "old/new" differences for ERPs to items associated with accurate episodic memory retrieval versus correctly rejected new items. ATD increased ERP voltage between 500 and 1400 ms post-stimulus particularly over posterior regions of the scalp, but there was no interaction with item type. Topographical analysis of the old/new difference revealed no significant treatment by site interaction. CONCLUSIONS: ATD impairs episodic memory recall with no effect on the magnitude or topography of the neural correlates of retrieval in healthy subjects. This suggests that the effects of ATD on recall may reflect an impairment of memory encoding and/or consolidation.