Evaluation of GABAergic and Glutamatergic Levels in the Dorsal Anterior Cingulate Cortex of Patients With Bipolar Disorder: A Cross-Sectional ¹H-MRS Study

Background: Imbalances between excitatory and inhibitory (E/I) neurotransmitters in the brain may contribute to the pathophysiology of bipolar disorder (BD). Proton magnetic resonance spectroscopy (¹H-MRS) measures glutamatergic neurometabolites and gamma-aminobutyric acid (GABA) as indices of E/I neurotransmission. Previous meta-analyses reported higher glutamatergic neurometabolite levels in the medial prefrontal cortex of BD, but findings on GABA levels in the anterior cingulate cortex (ACC) of BD patients remain inconsistent. Methods: We conducted a cross-sectional study using ¹H-MRS to compare GABA and glutamate plus glutamine (Glx) levels in the dorsal ACC (dACC) of 27 patients with BD and 27 age- and sex-matched healthy controls (HCs). We used the ¹H-MRS (3 T MRI, MEGAPRESS, 256 averages, TR = 1500 ms, TE = 68 ms). Clinical symptoms were evaluated using standardized rating scales. Statistical analyses were conducted to assess group differences in neurometabolite levels and to explore the associations between these neurometabolite levels and clinical symptom severity within the BD group. Results: No significant differences in dACC GABA levels, Glx levels, or Glx/GABA ratio were observed between the BD and HC groups. There were no significant differences within the BD group based on BD subtype (I or II) or clinical phase (depression or euthymic). Patients with lithium treatment had higher GABA levels compared to those without. Discussion: Our results suggest that GABAergic function in the dACC may not play a pivotal role in the pathophysiology of BD. Given possible GABAergic dysregulation in BD, further research using alternative methodologies is warranted to elucidate the pathological basis.