SEATTLE—Persons with primary insomnia have a 30% global reduction in gamma-aminobutyric acid (GABA) level, according to research presented at the 23rd Annual Meeting of the Associated Professional Sleep Societies. This preliminary finding, revealed with use of proton magnetic resonance spectroscopy (1H-MRS), is the first demonstration of a neurochemical difference in the brains of patients with primary insomnia compared with normal sleeping controls, commented John Winkelman, MD, PhD, Assistant Professor of Psychiatry at Harvard Medical School in Boston, and colleagues.
Sixteen nonmedicated patients with primary insomnia (eight women; mean age, 37.3) and 16 normal sleepers (seven women; mean age, 37.6) were assessed in a matched-groups, cross-sectional study conducted at two university hospitals. Primary insomnia was established via an unstructured clinical interview, the Structured Clinical Interview for DSM-IV (SCID), a sleep diary, actigraphy, and polysomnography. No subjects had substance abuse or dependence, mood or anxiety disorders, and none were taking hypnotic medication.
A Varian 4 Tesla MRI/spectroscopy scanner was used to collect 1H-MRS data. Samples from the basal ganglia, thalamus, and temporal, parietal, and occipital white matter and cortex were used to average global brain GABA levels.
Reduction in GABA Level
“Average GABA levels from sampled brain regions were reduced by nearly 30% in patients with primary insomnia compared to controls,” Dr. Winkelman, who is also an Associate Physician at the Division of Sleep Medicine, Brigham and Women’s Hospital in Boston, and colleagues, stated.
The authors observed no significant effects of age, gender, or BMI on GABA levels. “GABA levels were negatively correlated with wake after sleep onset on two independent polysomnography [tests],” reported the investigators. Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index global scores did not correlate with GABA levels in the primary insomnia group. However, self-reported sleep duration from the PSQI did correlate with GABA levels.
Neurobiology of Insomnia
“The high inverse correlations between GABA levels and polysomnography-derived wake after sleep onset in primary insomnia provide further confidence in the value of our GABA measures,” Dr. Winkelman and his colleagues noted. “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.”
—Laura Sassano