Abstract
Chronic insomnia is one of the most prevalent central nervous system disorders. It is characterized by increased arousal levels, however, the neurobiological causes and correlates of hyperarousal in insomnia remain to be further determined. In the current study, magnetic resonance spectroscopy was used in the morning and evening in a well-characterized sample of 20 primary insomnia patients (12 females; 8 males; 42.7 ± 13.4 years) and 20 healthy good sleepers (12 females; 8 males; 44.1 ± 10.6 years). The most important inhibitory and excitatory neurotransmitters of the central nervous system, γ-aminobutyric acid (GABA) and glutamate/glutamine (Glx), were assessed in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). The primary hypothesis, a diurnal effect on GABA levels in patients with insomnia, could not be confirmed. Moreover, the current results did not support previous findings of altered GABA levels in individuals with insomnia. Exploratory analyses, however, suggested that GABA levels in the ACC may be positively associated with habitual sleep duration, and, thus, reduced GABA levels may be a trait marker of objective sleep disturbances. Moreover, there was a significant GROUP x MEASUREMENT TIME interaction effect on Glx in the DLPFC with increasing Glx levels across the day in the patients but not in the control group. Therefore, Glx levels may reflect hyperarousal at bedtime in those with insomnia. Future confirmatory studies should include larger sample sizes to investigate brain metabolites in different subgroups of insomnia.
Highlights
Chronic insomnia, one of the most prevalent mental disorders, is characterized by difficulties in initiating or maintaining sleep and is associated with clinically significant distress or impairment of daytime functioning [1]
As preliminary work at the Department of Radiology of the University Medical Center Freiburg showed high test-retest reliability for the assessment of GABA+ levels in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) using a MEGA-PRESS sequence (Mescher-Garwood point-resolved spectroscopy sequence [25]) in a single subject, the current study focused on these specific brain areas
Beck Depression Inventory (BDI) scores were increased in primary insomnia (PI) patients, and the group difference was reduced to a statistical trend when excluding the two sleep-related questions from the BDI (PI patients: 4.6 ± 3.6, good sleeper controls: 2.5 ± 3.2, t = -2.00, p = 0.052)
Summary
One of the most prevalent mental disorders, is characterized by difficulties in initiating or maintaining sleep and is associated with clinically significant distress or impairment of daytime functioning [1]. The prevalence of the disorder is approximately 6% of PLOS ONE | DOI:10.1371/journal.pone.0156771. Magnetic Resonance Spectroscopy in Insomnia and the University of Freiburg in the funding programme Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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