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VOLUME 31, ISSUE 11

RAPID PUBLICATION
Reduced Brain GABA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS)

John W. Winkelman, MD, PhD1,3; Orfeu M. Buxton, PhD1; J. Eric Jensen, PhD2,3; Kathleen L. Benson, PhD1; Shawn P. O’Connor, BA1; Wei Wang, MA1; Perry F. Renshaw, MD, PhD2,3

1Division of Sleep Medicine, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA; 2Brain Imaging Center, McLean Hospital, Belmont, MA; 3Department of Psychiatry, Harvard Medical School, Boston, MA



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Study Objectives:

Both basic and clinical data suggest a potential significant role for GABA in the etiology and maintenance of primary insomnia (PI). Proton magnetic resonance spectroscopy (1H-MRS) can non-invasively determine GABA levels in human brain. Our objective was to assess GABA levels in unmedicated individuals with PI, using 1H-MRS.

Design and Setting:

Matched-groups, cross-sectional study conducted at two university-based hospitals.

Participants:

Sixteen non-medicated individuals (8 women) with PI (mean age = 37.3 +/- 8.1) and 16 (7 women) well-screened normal sleepers (mean age = 37.6 +/- 4.5).

Methods and Measurements:

PI was established with an unstructured clinical interview, a Structured Clinical Interview for DSM-IV (SCID), sleep diary, actigraphy and polysomnography (PSG). 1H-MRS data were collected on a Varian 4 Tesla magnetic resonance imaging/spectroscopy scanner. Global brain GABA levels were averaged from samples in the basal ganglia, thalamus, and temporal, parietal, and occipital white-matter and cortex.

Results:

Average brain GABA levels were nearly 30% lower in patients with PI (.18 +/- .06) compared to controls (.25 +/- .11). GABA levels were negatively correlated with wake after sleep onset (WASO) on two independent PSGs (r = -0.71, p = 0.0024 and -0.70, p = 0.0048).

Conclusions:

Our preliminary finding of a global reduction in GABA in non-medicated individuals with PI is the first demonstration of a neurochemical difference in the brains of those with PI compared to normal sleeping controls. 1H-MRS is a valuable tool to assess GABA in vivo, and may provide a means to shed further light on the neurobiology of insomnia.
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