ADVERTISEMENT
CURRENT ISSUE
APRIL 2014
KINDLE EDITION


SLEEP Seeking New Editor

The APSS is seeking qualified candidates for editor-in-chief of SLEEP



SEARCH JOURNAL ARCHIVES


SEARCH PUBMED


MANUSCRIPT SUBMISSIONS


SUBSCRIBE TO SLEEP

CONTINUING MEDICAL EDUCATION


ADVERTISE WITH US


ABOUT SLEEP

ABSTRACT SUPPLEMENTS


ACCEPTED PAPERS
Bookmark and Share         RSS Feed

VOLUME 33, ISSUE 03

SLEEP AND CIRCADIAN EFFECTS FROM LOSS OF SEROTONIN
Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin

Smaranda Leu-Semenescu, MD1,7; Isabelle Arnulf, MD, PhD1,7; Caroline Decaix, PhD2; Fathi Moussa, PhD3; Fabienne Clot, PhD4; Camille Boniol, RN2; Yvan Touitou, PhD5; Richard Levy, MD, PhD2; Marie Vidailhet, MD6,7; Emmanuel Roze, MD, PhD6,8

1Sleep Disorders Unit, Pitié-Salpêtrière Hospital, AP-HP, Paris, France; 2Department of Neurology, Saint-Antoine Hospital, AP-HP, Paris 6 University, Paris, France; 3Department of Biochemistry, Trousseau Hospital, AP-HP, Paris 6 University, Paris, France; 4Department of Genetics and Cytogenetics, Pitié-Salpêtrière Hospital, AP-HP, Paris, France; 5U713, INSERM, Paris 6 University, Paris, France; 6Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Paris 6 University, Paris, France; 7UMR 975, INSERM, Paris 6 University, Paris, France; 8UMRS 952, INSERM, Paris 6 University, Paris, France



  Expand  Table of Contents    
Text size:  

Background: 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.
Objective: We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency.
Patient: The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency.
Methods: 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.
Results: 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, attention/executive 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.
Conclusion: In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.
Keywords: Sepiapterin reductase deficiency, hypersomnia, melatonin, ultradian sleep-wake rhythm, tetrahydrobiopterin, serotonin

Expand  Table of Contents
ADVERTISEMENT
Classifieds View SLEEP 2011 Poster Presentations Online