Energetic and cell membrane metabolic products in patients with primary Insomnia: A 31-Phosphorus magnetic resonance spectroscopy study at 4 Tesla

David G. Harper, David T. Plante, J. Eric Jensen, Caitlin Ravichandran, Orfeu M. Buxton, Kathleen L. Benson, Shawn P. Oconnor, Perry F. Renshaw, John W. Winkelman

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Study Objectives: 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. Design and Setting: Matched-groups, cross-sectional study performed at two university-based hospitals. Patients: 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). Measurements: 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.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalSleep
Volume36
Issue number4
DOIs
StatePublished - Apr 1 2013

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Sleep Initiation and Maintenance Disorders
Phosphorus
Magnetic Resonance Spectroscopy
Cell Membrane
Phosphocreatine
Sleep
Phosphorylcholine
Nucleosides
Adenosine Triphosphate
Actigraphy
Interviews
Polysomnography
Phosphatidylcholines
Diagnostic and Statistical Manual of Mental Disorders
Energy Metabolism
Research Design
Cross-Sectional Studies
Maintenance
Gray Matter

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Physiology (medical)

Cite this

Harper, David G. ; Plante, David T. ; Jensen, J. Eric ; Ravichandran, Caitlin ; Buxton, Orfeu M. ; Benson, Kathleen L. ; Oconnor, Shawn P. ; Renshaw, Perry F. ; Winkelman, John W. / Energetic and cell membrane metabolic products in patients with primary Insomnia : A 31-Phosphorus magnetic resonance spectroscopy study at 4 Tesla. In: Sleep. 2013 ; Vol. 36, No. 4. pp. 493-500.
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title = "Energetic and cell membrane metabolic products in patients with primary Insomnia: A 31-Phosphorus magnetic resonance spectroscopy study at 4 Tesla",
abstract = "Study Objectives: 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. Design and Setting: Matched-groups, cross-sectional study performed at two university-based hospitals. Patients: 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). Measurements: 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.",
author = "Harper, {David G.} and Plante, {David T.} and Jensen, {J. Eric} and Caitlin Ravichandran and Buxton, {Orfeu M.} and Benson, {Kathleen L.} and Oconnor, {Shawn P.} and Renshaw, {Perry F.} and Winkelman, {John W.}",
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Harper, DG, Plante, DT, Jensen, JE, Ravichandran, C, Buxton, OM, Benson, KL, Oconnor, SP, Renshaw, PF & Winkelman, JW 2013, 'Energetic and cell membrane metabolic products in patients with primary Insomnia: A 31-Phosphorus magnetic resonance spectroscopy study at 4 Tesla', Sleep, vol. 36, no. 4, pp. 493-500. https://doi.org/10.5665/sleep.2530

Energetic and cell membrane metabolic products in patients with primary Insomnia : A 31-Phosphorus magnetic resonance spectroscopy study at 4 Tesla. / Harper, David G.; Plante, David T.; Jensen, J. Eric; Ravichandran, Caitlin; Buxton, Orfeu M.; Benson, Kathleen L.; Oconnor, Shawn P.; Renshaw, Perry F.; Winkelman, John W.

In: Sleep, Vol. 36, No. 4, 01.04.2013, p. 493-500.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Energetic and cell membrane metabolic products in patients with primary Insomnia

T2 - A 31-Phosphorus magnetic resonance spectroscopy study at 4 Tesla

AU - Harper, David G.

AU - Plante, David T.

AU - Jensen, J. Eric

AU - Ravichandran, Caitlin

AU - Buxton, Orfeu M.

AU - Benson, Kathleen L.

AU - Oconnor, Shawn P.

AU - Renshaw, Perry F.

AU - Winkelman, John W.

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Study Objectives: 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. Design and Setting: Matched-groups, cross-sectional study performed at two university-based hospitals. Patients: 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). Measurements: 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.

AB - Study Objectives: 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. Design and Setting: Matched-groups, cross-sectional study performed at two university-based hospitals. Patients: 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). Measurements: 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.

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