title: Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.
abstract: OBJECTIVE
  Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population.
  
  
  METHODS
  We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview.
  
  
  RESULTS
  An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls.
  
  
  CONCLUSIONS
  We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans.
authors.affiliation: Sleep Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Barateau
authors.affiliation: Inserm, U1061, Montpellier, France; Université Montpellier 1, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jaussent
authors.affiliation: Sleep Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, France.|Inserm, U1061, Montpellier, France; Université Montpellier 1, Montpellier, France.|National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Boutrel
authors.affiliation: National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Paris, France.|Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, AP-HP, Brain Research Institute (CRICM-UPMC-Paris6; Inserm UMR_S 975; CNRS UMR 7225), Sorbonne Universities, UPMC Univ Paris 06, Paris, France.
authors.forename: Smaranda
authors.initials: S
authors.lastname: Leu-Semenescu
authors.affiliation: National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Paris, France.|Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, AP-HP, Brain Research Institute (CRICM-UPMC-Paris6; Inserm UMR_S 975; CNRS UMR 7225), Sorbonne Universities, UPMC Univ Paris 06, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnulf
authors.affiliation: Sleep Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, France.|Inserm, U1061, Montpellier, France; Université Montpellier 1, Montpellier, France.|National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D001143:Arousal; D016022:Case-Control Studies; D066249:Craving; D003430:Cross-Sectional Studies; D006970:Disorders of Excessive Somnolence / Q000453:epidemiology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D020177:Idiopathic Hypersomnia / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009042:Motivation; D009290:Narcolepsy / Q000453:epidemiology*; D000068797:Orexins / Q000172:deficiency / Q000378:metabolism; D012907:Smoking; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000068797:Orexins
keywords: addiction; hypersomnia; hypocretin/orexin; narcolepsy; substance abuse