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

Abstract

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 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.

Figure 1

Sagittal image at 4 T depicting the placement of the 30mm thick MRSI slab.

Figure 2

J-resolved spectra from the parieto-occipital region of a healthy control subject. Spectra are exponentially-filtered with 4Hz filtering and the J = 7.5Hz spectrum is exaggerated in vertical scale for comparison to the J = 0.0Hz.

Figure 3

GABA / Creatine ratios in Primary Insomnia and normal sleeping controls

Figure 4

GABA vs. WASO scatterplots in Primary Insomnia on Sleep Screen (A) and Inpatient (B) PSGs. WASO = wake time after sleep onset.