Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS).
OBJECTIVE
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.


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


METHODS
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
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 imagingl 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.
Winkelman
John W
JW
Division of Sleep Medicine, Brigham & Women's Hospital, Harvard Medical School, 1505 Commonwealth Avenue, Brighton, MA 02135, USA. JWWinkelman@partners.org
Buxton
Orfeu M
OM
Jensen
J Eric
JE
Benson
Kathleen L
KL
O'Connor
Shawn P
SP
Wang
Wei
W
Renshaw
Perry F
PF
D000328:Adult; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D003430:Cross-Sectional Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D017286:Polysomnography; D011522:Protons; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis* / Q000378:metabolism*; D012895:Sleep, REM / Q000502:physiology; D027981:Symporters / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D011522:Protons; D027981:Symporters; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters