Sleep and rhythm consequences of a genetically induced loss of serotonin

Sleep Disorders Unit, Pitié-Salpêtrière Hospital, AP-HP Paris, France.
Sleep (Impact Factor: 4.59). 03/2010; 33(3):307-14.
Source: PubMed


A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied.
We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency.
The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency.
A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed.
Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition.
In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

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Available from: Richard Levy, Jun 17, 2014
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    • "Mild hypersomnia with prolonged sleep time (704 min) and ultradian sleep–wake rhythm with sleep occurrence every 11.8 ± 5.3 h were documented. Supplementation with 5-hydroxytryptophan resulted in improved cognition as a consequence of reduction of total sleep time to 540 min and restoration of serotonin metabolism in the CSF, serum melatonin profile, and circadian sleep–wake rhythm (62). "
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    • "The product of this enzyme, tetrahydrobiopterin (BH4), is required by aromatic amino acid hydroxylases. BH4 deficiency causes, beside other effects, poor synthesis of 5-hydroxytryptophan and, thus, serotonin, with the further consequence of a flattened melatonin rhythm [20]. "
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