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Rationale: Acute tryptophan depletion (ATD) decreases levels of central serotonin. ATD thus enables the cognitive effects of serotonin to be studied, with implications for the understanding of psychiatric conditions, including depression., Objective: To determine the role of serotonin in conscious (explicit) and unconscious/incidental processing of emotional information., Materials and Methods: A randomized, double-blind, cross-over design was used with 15 healthy female participants. Subjective mood was recorded at baseline and after 4 h, when participants performed an explicit emotional face processing task, and a task eliciting unconscious processing of emotionally aversive and neutral images presented subliminally using backward masking., Results: ATD was associated with a robust reduction in plasma tryptophan at 4 h but had no effect on mood or autonomic physiology. ATD was associated with significantly lower attractiveness ratings for happy faces and attenuation of intensity/arousal ratings of angry faces. ATD also reduced overall reaction times on the unconscious perception task, but there was no interaction with emotional content of masked stimuli. ATD did not affect breakthrough perception (accuracy in identification) of masked images., Conclusions: ATD attenuates the attractiveness of positive faces and the negative intensity of threatening faces, suggesting that serotonin contributes specifically to the appraisal of the social salience of both positive and negative salient social emotional cues. We found no evidence that serotonin affects unconscious processing of negative emotional stimuli. These novel findings implicate serotonin in conscious aspects of active social and behavioural engagement and extend knowledge regarding the effects of ATD on emotional perception.

Background: Neuroendocrine studies of brain serotonin (5-HT) function in depression generally show evidence of impaired 5-HT function but it is disputed whether or not this impairment resolves with clinical recovery., Aims: To use the endocrine response to the selective 5-HT reuptake inhibitor, citalopram, to study brain 5-HT function in acute and recovered depressed subjects relative to healthy controls., Method: We used a double-blind, placebo-controlled design to measure the prolactin and cortisol responses to citalopram (10 mg intravenously) in patients with major depression, in unmedicated subjects recovered from depression and in healthy controls., Results: The prolactin responses to citalopram were blunted similarly in both acutely depressed and recovered subjects. The cortisol responses were blunted in the acutely depressed patients but not in the recovered subjects., Conclusions: Our data support the proposal that some aspects of impaired 5-HT neurotransmission may be trait markers of vulnerability to depression. The recovery of the cortisol response to citalopram may indicate resolution of hypothalamic-pituitary-adrenal axis dysfunction.

The β-adrenoceptor antagonist, penbutolol, is an effective serotonin[sub 1A] (5-HT[sub 1A] ) receptor antagonist in the rat and through this action enhances the ability of selective serotonin re-uptake inhibitors (SSRIs) to increase levels of serotonin in terminal fields. In healthy volunteers, penbutolol (40 mg orally), produced a modest attenuation of the prolactin response to the 5-HT[sub 1A] receptor antagonist, buspirone (30 mg orally), but did not antagonise the hypothermic response. Furthermore, penbutolol addition (40 mg daily for 3 weeks) failed to improve the symptomatology of 10 depressed patients who had shown an inadequate clinical response to serotonergic antidepressants. These preliminary data suggest that at the typical dose used to treat hypertension, penbutolol does not antagonise 5-HT[sub 1A] autoreceptors in humans and does not augment the effect of serotonergic antidepressants in treatment non-responders. Copyright © 1999 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Effective neuroendocrine probes of 5-HT[sub 1B] and 5-HT[sub 1D] receptor function may facilitate investigation of the role of these receptor subtypes in the pathophysiology of depression and the mode of action of antidepressant medication. Objective: To investigate the neuroendocrine profile of the 5-HT[sub 1B/1D] receptor agonist, zolmitriptan, in healthy volunteers. Methods: Twelve subjects entered a double-blind, placebo-controlled, cross-over design study of zolmitriptan (5 mg orally). Blood samples were taken at 15-min intervals for assay of prolactin and growth hormone. A further six healthy men were recruited to an equivalent study to examine the effect of ketanserin (a 5-HT receptor antagonist with some preference for 5-HT[sub 1D] over 5-HT[sub 1B] receptors) on the growth hormone response to zolmitriptan. Results: Zolmitriptan significantly increased plasma growth hormone but had no effect on plasma prolactin or oral temperature. The increase in growth hormone produced by zolmitriptan was significantly attenuated by ketanserin. Conclusions: We suggest that the ability of triptans such as zolmitriptan, sumatriptan and rizatriptan to increase plasma growth hormone is mediated by their common agonist activity at postsynaptic 5-HT[sub 1D] receptors. [ABSTRACT FROM AUTHOR]

Abstract Rationale: A 44-base-pair insertion/deletion polymorphism in the promoter region of the human serotonin (5-HT) transporter (5-HTT) gene gives rise to a biallelic polymorphism designated long (l) and short (s). The s variant is associated with a lower expression of 5-HTT sites and a reduced efficiency of 5-HT reuptake. Objective: The aim of the present study was to determine whether the increase in brain 5-HT function produced by acute 5-HT reuptake blockade is influenced by the 5-HTT promoter Ils polymorphism. Methods: We measured the increase in plasma prolactin that follows acute administration of the tricyclic antidepressant clomipramine as an index of 5-HT neurotransmission in 14 healthy female subjects (7 with ss genotype and 7 with Il genotype) using a placebo-controlled crossover design. Results: Clomipramine-induced prolactin release was significantly greater in subjects with the Il genotype. Conclusion: Our findings suggest that acute 5-HT reuptake blockade produces a greater increase in 5-HT neurotransmission in subjects with the Il genotype than in those with an ss genotype. These results are consistent with clinical data indicating that subjects with an ss genotype may have a poorer therapeutic response to selective serotonin reuptake inhibitor (SSRI) monotherapy. [ABSTRACT FROM AUTHOR]