title: Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression.
abstract: OBJECTIVE
  There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.
  
  
  METHODS
  Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro.
  
  
  RESULTS
  In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5%, n = 593; p = 0.009; odds ratio, OR: 1.46) as compared to ethnically matched controls (3.8%, n = 2912), while schizophrenia patients (4.1%, n = 503) did not differ. In vitro, the Pro7 substitution appeared to be associated with reduced levels of NPY without affecting its mRNA level.
  
  
  CONCLUSIONS
  The Leu7Pro variation may increase the risk of major depression, possibly by affecting the biosynthesis of NPY.
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Koefoed
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: David P D
authors.initials: DP
authors.lastname: Woldbye
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas V O
authors.initials: TV
authors.lastname: Hansen
authors.affiliation: Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark and Research Unit for Psychiatric Rehabilitation, Mental Health Centre Ballerup, Ballerup, Denmark.
authors.forename: Lene F
authors.initials: LF
authors.lastname: Eplov
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Søren H
authors.initials: SH
authors.lastname: Christiansen
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars V
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Katja
authors.initials: K
authors.lastname: Kaipio
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Ullamari
authors.initials: U
authors.lastname: Pesonen
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fahmy
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Erling
authors.initials: E
authors.lastname: Mellerup
authors.affiliation: Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark.
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Jakobsen
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Elsebeth S
authors.initials: ES
authors.lastname: Hansen
authors.affiliation: Center for Integrated Molecular Brain Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Bukh
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Bock
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Lindberg
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ann S
authors.initials: AS
authors.lastname: Kristensen
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Dam
authors.affiliation: Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Als
authors.affiliation: Mental Health Centre Amager, Copenhagen, Denmark.
authors.forename: August G
authors.initials: AG
authors.lastname: Wang
authors.affiliation: Molecular Neuropharmacology Group and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Gether
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tom G
authors.initials: TG
authors.lastname: Bolwig