Biochemical stress of caring.

BACKGROUND: Carers of patients with clinical dementia have increased rates of depressive illness but the biological mechanisms by which the stress of caring can lead to mood disorders is not well understood. METHODS: We recruited 30 full-time carers of patients with dementia and 28 age and gender-matched controls. None of the subjects were suffering from a significant depressive disorder. We measured salivary cortisol at four time points throughout a single day and also took a single fasting morning blood sample for plasma tryptophan. RESULTS: Salivary cortisol levels were significantly higher in carers than controls at 12.00 h and 22.00 h. Plasma total tryptophan but not free tryptophan levels were significantly lower in carers. CONCLUSIONS: The changes found in these non-depressed carers were essentially similar to those in patients with major depression. We suggest that increased cortisol secretion and lowered tryptophan availability increase the risk of mood disorders in carers.

Decreased 5-HT-mediated prolactin release in major depression.

The prolactin response to intravenous clomipramine, a 5-HT uptake inhibitor, was significantly attenuated in 12 patients with major depression. In contrast, in a further 12 depressed patients, the PRL responses to thyrotropin-releasing hormone, which acts directly on the pituitary to release PRL, were not reduced. These findings suggest that the reduction in 5-HT-mediated PRL release seen in depressed patients is due to an impairment of brain 5-HT function rather than a pituitary abnormality.

Sleep and 5-HT2 receptor sensitivity in recovered depressed patients.

The increase in slow wave sleep which followed administration of the 5-HT2 receptor antagonist, ritanserin, was not significantly different between a group of 12 recovered, drug free depressed patients and a group of 12 health matched controls. The results suggests that there is no underlying abnormality in the 5-HT2 receptor regulation of slow wave sleep in recovered depressives, and that abnormalities in this measure reported previously in such patients may have been caused by use of concomitant tricyclic antidepressant medication. The baseline sleep parameters did not differ between recovered depressives and controls with the exception of stage 1 sleep, which was increased in the patient group.

Slow wave sleep and 5-HT2 receptor sensitivity in generalised anxiety disorder: a pilot study with ritanserin.

Eight patients with generalised anxiety disorder (GAD) and eight matched healthy controls had their polysomnogram measured on two occasions separated by 1 week. On one occasion they received the 5-HT2 receptor antagonist, ritanserin (5 mg orally) and on the other matching placebo. The increase in slow wave sleep produced by ritanserin was the same in GAD patients as in healthy controls. These findings do not support the hypothesis that GAD is associated with a generalised hypersensitivity of brain 5-HT2 receptors; however, the present data cannot exclude the presence of a regionally specific change in this receptor subtype in anxiety disorders.

Dose-related effects of selective 5-HT2 receptor antagonists on slow wave sleep in humans.

The effects of the selective 5-HT2 receptor antagonists, ritanserin (1, 5 and 10 mg) and ICI 169.369 (50 and 100 mg), were studied on the sleep EEG of healthy volunteers using home-based Medilog 9000 cassette monitoring. Ritanserin (5 and 10 mg) produced a significant increase in slow wave sleep (SWS) while ICI 169,369 also increased SWS but only at a dose of 100 mg. These findings are consistent with the proposal that selective 5-HT2 receptor blockade increases SWS in humans; however, the data cannot exclude involvement of the closely related 5-HT1c receptor in this effect.