Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy

Biol Psychiatry. 2005 Dec 15;58(12):969-73. doi: 10.1016/j.biopsych.2005.05.017. Epub 2005 Jul 25.


Background: There is growing evidence that the brain gamma-aminobutyric acid (GABA) system is involved in depression. Lowered plasma GABA levels were identified as a traitlike abnormality found in patients with remitted unipolar depression and in healthy first-degree relatives of patients with unipolar depression. Major depressive disorder has been associated with neuroimaging and neuropathological abnormalities in the prefrontal cortex by various types of evidence. As a result, the current study investigates whether GABA levels in the prefrontal cortex differ between unmedicated subjects with remitted major depressive disorder (rMDD) and healthy control subjects.

Methods: Sixteen rMDD subjects and 15 healthy control subjects underwent magnetic resonance spectroscopy. We used a 3 Tesla GE whole body scanner with a homogeneous resonator coil providing a homogenous radiofrequency field and capability of obtaining measurement from the prefrontal cortex. Gamma-aminobutyric acid levels were measured in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex.

Results: There was no difference in GABA concentrations between rMDD subjects and healthy control subjects in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. Secondary analyses provided preliminary evidence for a negative relationship between the glutamate/glutamine (Glx)/GABA ratio and age of onset of major depression in the ventromedial prefrontal cortex.

Conclusions: This result suggests that GABA levels in the prefrontal cortex, if found to be reduced in symptomatic depression, do not represent a persistent characteristic of major depression. Further research is needed to determine brain GABA levels in different brain regions, in different stages of depressive illness, and in different depressive subtypes.

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Female
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Middle Aged
  • Prefrontal Cortex / metabolism*
  • Psychiatric Status Rating Scales
  • gamma-Aminobutyric Acid / metabolism*


  • Antidepressive Agents
  • Glutamine
  • Glutamic Acid
  • gamma-Aminobutyric Acid