title: Energetic and cell membrane metabolic products in patients with primary insomnia: a 31-phosphorus magnetic resonance spectroscopy study at 4 tesla.
abstract: OBJECTIVE
  Primary insomnia (PI) is a sleep disorder characterized by difficulty with sleep initiation, maintenance, and/or the experience of nonrestorative sleep combined with a subsequent impairment of daytime functioning. The hyperarousal hypothesis has emerged as the leading candidate to explain insomnia symptoms in the absence of specific mental, physical, or substance-related causes. We hypothesized that the cellular energetic metabolites, including beta nucleoside triphosphate, which in magnetic resonance spectroscopy approximates adenosine triphosphate (ATP), and phosphocreatine (PCr), would show changes in PI reflecting increased energy demand.
  
  
  METHODS
  Matched-groups, cross-sectional study performed at two university-based hospitals.
  
  
  METHODS
  Sixteen medication-free individuals (eight males, eight females; mean ± standard deviation (SD) age = 37.2 ± 8.4 y) with PI and 16 good sleepers (nine males, seven females; mean ± SD age = 37.6 ± 4.7 y).
  
  
  METHODS
  Diagnosis was established for all individuals by unstructured clinical interview, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), sleep diary, and actigraphy. Polysomnography was collected in individuals with PI. Phosphorous magnetic resonance spectroscopy (31P MRS) data were collected on all individuals at 4 Tesla. We assessed cell membrane (anabolic precursors and catabolic metabolites) and bioenergetic (ATP, phosphocreatine) metabolites in gray matter and white matter to determine their relationship to the presence and severity of PI.
  
  
  RESULTS
  Individuals with PI showed lower phosphocreatine in gray matter and an unexpected decrease of phosphocholine, a precursor of the cell membrane compound phosphatidylcholine, in white matter. In addition, there was a trend toward a negative association between polysomnographically determined wake after sleep onset and gray matter beta-nucleoside triphosphate and white matter phosphocholine in the primary insomnia group.
  
  
  CONCLUSIONS
  These results support the hyperarousal hypothesis in PI based on lower phosphocreatine in gray matter in the PI group.
authors.affiliation: Geriatric Psychiatry Program, Harvard Medical School, Boston, MA, USA. dharper@mclean.harvard.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Harper
authors.forename: David T
authors.initials: DT
authors.lastname: Plante
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
authors.forename: Caitlin
authors.initials: C
authors.lastname: Ravichandran
authors.forename: Orfeu M
authors.initials: OM
authors.lastname: Buxton
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Benson
authors.forename: Shawn P
authors.initials: SP
authors.lastname: O'Connor
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: John W
authors.initials: JW
authors.lastname: Winkelman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D017286:Polysomnography / Q000379:methods; D007319:Sleep Initiation and Maintenance Disorders / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate
keywords: Adenosine triphosphate (ATP); long-term potentiation; phosphocholine; phosphocreatine; sleep; spectroscopy
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