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Reduced Brain GABA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS) - Source: Sleep, Nov 2008

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By John W Winkelman, MD, PhD, et al. • • November 13, 2008

[GABA (gamma-aminobutyric acid) is naturally made in the brain from the amino acid glutamate, helped by vitamin B6. It is the brain’s chief ‘inhibitory’ neurotransmitter, known to help induce relaxation, analgesia, and sleep.]

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). [Less GABA, increased wake after sleep.]

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.

Source: Sleep, Nov 2008; 31(11). Winkelman JW, Buxton OM, Jensen JE, Benson KL, O’Connor SP, Wang W, Renshaw PF. Division of Sleep Medicine, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Brain Imaging Center, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, USA. [E-mail:]

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