Anterior Cingulate Cortex Glutamatergic Metabolites and Mood Stabilizers in Euthymic Bipolar I Disorder Patients: A Proton Magnetic Resonance Spectroscopy Study

Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Dec;3(12):985-991. doi: 10.1016/j.bpsc.2018.02.007. Epub 2018 Mar 31.

Abstract

Background: Bipolar disorder is a chronic and recurrent illness characterized by depressive and manic episodes. Proton magnetic resonance spectroscopy (1H-MRS) studies have demonstrated glutamate (Glu) system abnormalities in BD, but it is unclear how Glu varies among mood states and how medications modulate it. The objective of this study was to investigate the influence of mood stabilizers on anterior cingulate cortex Glu levels using 1H-MRS during euthymia.

Methods: One hundred twenty-eight bipolar I disorder (BDI) euthymic subjects and 80 healthy control subjects underwent 3T brain 1H-MRS imaging examination including acquisition of an anterior cingulate cortex single voxel (8 cm3) 1H-MRS, based on a point resolved spectroscopy (PRESS) sequence with an echo time of 80 ms and a repetition time of 1500 ms (BIPUSP MRS study). The Glu system was described by measuring Glu and the sum of Glu and glutamine (Glx) using creatine (Cre) as a reference.

Results: Euthymic BDI subjects presented with higher ratios of Glu/Cre and Glx/Cre compared to healthy control subjects. Glu/Cre ratios were lower among patients using anticonvulsants, while Glx/Cre did not differ between the two groups. Lithium, antipsychotics, and antidepressants did not influence Glu/Cre or Glx/Cre.

Conclusions: We reported Glu/Cre and Glx abnormalities in the largest sample of euthymic BDI patients studied by 1H-MRS to date. Our data indicate that both Glu/Cre and Glx/Cre are elevated in BDI during euthymia regardless of medication effects, reinforcing the hypothesis of glutamatergic abnormalities in BD. Furthermore, we found an effect of anticonvulsants on Glu/Cre during euthymia, which might indicate a mechanism of mood stabilization in BD.

Keywords: Anticonvulsants; Bipolar disorder; Euthymia; Glutamate; Glx; Magnetic resonance spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects*
  • Anticonvulsants / metabolism
  • Anticonvulsants / pharmacology
  • Antidepressive Agents / metabolism
  • Antidepressive Agents / pharmacology
  • Antimanic Agents / metabolism
  • Antimanic Agents / pharmacology
  • Antipsychotic Agents / metabolism
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Brain / drug effects
  • Brain / metabolism
  • Cyclothymic Disorder / drug therapy
  • Female
  • Glutamic Acid / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Proton Magnetic Resonance Spectroscopy* / methods
  • Young Adult

Substances

  • Anticonvulsants
  • Antidepressive Agents
  • Antimanic Agents
  • Antipsychotic Agents
  • Glutamic Acid