The tryptophan depletion test: Impact on sleep in healthy subjects and patients with obsessive-compulsive disorder

The tryptophan depletion test is a research tool to study the functional consequences of decreasing the brain serotonin metabolism. Since serotonin is involved in sleep regulation and assumed to be of high importance in the etiology of psychiatric disorders, the acute polysomnographic effects of tryptophan depletion were studied in healthy subjects and patients with obsessive compulsive disorder (OCD). According to the reciprocal interaction model of non-REM and REM-sleep regulation we expected that tryptophan depletion in healthy controls should provoke alterations of sleep similar to depression, whereas we assumed that these effects would be more pronounced in patients with OCD. Methods: 12 healthy subjects with a mean age of 34 years and 12 patients suffering from OCD with a mean age of 30 years had 4 polysomnographic investigations. After 1 adaption and 1 baseline night subjects received a low proteine diet on day 3 and 4 until midday. On day 4 at 18.00h subjects ingested an aminoacid mixture devoid of tryptophan. This procedure resulted in a decrease of 85% in healthy subjects and 80% in OCD patients at 22.00h. Results: The tryptophan depletion led to more pronounced disturbances of sleep continuity in OCD patients than in healthy subjects in terms of an increase of wake time and a decrease of total sleep time. In both groups a decrease of sleep stage 2 could be observed. Healthy subjects showed significant alterations of phasic REM parameters as REM density and total number of rapid eye movements, what was not the case for OCD patients. Conclusions: Our results indicate the important role of the serotonergic system for sleep maintainance and the phasic aspects of REM sleep. Furthermore our data demonstrate that the tryptophan depletion test is a useful tool to evaluate the hypothesis of a serotonergic involvement in sleep regulation and the etiology of psychiatric disorders.