An Objective Short Sleep Insomnia Disorder Subtype Is Associated With Reduced Brain Metabolite Concentrations In Vivo: A Preliminary Magnetic Resonance Spectroscopy Assessment

Christopher B Miller; Caroline D Rae; Michael A Green; Brendon J Yee; Christopher J Gordon; Angela L D'Rozario; Simon D Kyle; Colin A Espie; Ronald R Grunstein; Delwyn J Bartlett

doi:10.1093/sleep/zsx148

An Objective Short Sleep Insomnia Disorder Subtype Is Associated With Reduced Brain Metabolite Concentrations In Vivo: A Preliminary Magnetic Resonance Spectroscopy Assessment

Sleep. 2017 Nov 1;40(11). doi: 10.1093/sleep/zsx148.

Authors

Christopher B Miller^{1

2}, Caroline D Rae^{3

4}, Michael A Green³, Brendon J Yee^{1

2

5}, Christopher J Gordon^{1

6}, Angela L D'Rozario^{1

7}, Simon D Kyle⁸, Colin A Espie⁸, Ronald R Grunstein^{1

2

5}, Delwyn J Bartlett^{1

2}

Affiliations

¹ Woolcock Institute of Medical Research, CIRUS, Centre for Sleep and Chronobiology, Sydney, New South Wales, Australia.
² Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
³ Neuroscience Research Australia, Randwick, New South Wales, Australia.
⁴ School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
⁵ Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia.
⁶ Sydney Nursing School, The University of Sydney, Sydney, New South Wales, Australia.
⁷ School of Psychology, Faculty of Science, Brain and Mind Centre and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
⁸ Nuffield Department of Clinical Neurosciences, The University of Oxford, Oxford, UK.

PMID: 28958033
DOI: 10.1093/sleep/zsx148

Abstract

Objectives: To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs).

Methods: PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine.

Results: Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p < .05, d = .80-.99). Creatine displayed a nonsignificant mean reduction in I-SSD compared with I-NSD (p = .05, d = .58). Glutamine was reduced in I-SSD compared with controls (p < .05, d = .93). There were no differences in metabolites between all (I-SSD and I-NSD) insomnia patients and controls. In patients with insomnia, LOCC glutamine concentrations were found to be positively correlated with TST (r = .43, p < .05) and negatively correlated with wake-time after sleep onset (r = -.40, p < .05).

Conclusions: Results indicate that I-SSD is associated with reduced brain metabolites in the LOCC compared with I-NSD and control concentrations of aspartate, glutamine, and creatine.

Clinical trial registration: Insomnia MRS imaging sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853.

Trial identification number: 12612000050853.

Keywords: brain imaging and phenotyping; insomnia; magnetic resonance spectroscopy; sleep and the brain.

MeSH terms

Adult
Aspartic Acid / analogs & derivatives
Aspartic Acid / metabolism
Brain / metabolism*
Case-Control Studies
Creatine / metabolism
Female
Glutamic Acid / metabolism
Glutamine / metabolism
Gyrus Cinguli / metabolism
Humans
Magnetic Resonance Spectroscopy*
Male
Middle Aged
Occipital Lobe / metabolism
Polysomnography
Prefrontal Cortex / metabolism
Sleep
Sleep Initiation and Maintenance Disorders / diagnosis
Sleep Initiation and Maintenance Disorders / metabolism*
Sleep Initiation and Maintenance Disorders / physiopathology
Time Factors
Young Adult

Substances

Glutamine
Aspartic Acid
Glutamic Acid
Creatine

Associated data

ANZCTR/ACTRN12612000050853