Lithium-associated anterior cingulate neurometabolic profile in euthymic Bipolar I disorder: A 1H-MRS study

J Affect Disord. 2018 Dec 1:241:192-199. doi: 10.1016/j.jad.2018.08.039. Epub 2018 Aug 10.

Abstract

Objective: In the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy (1H-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo. The objective of this study was to investigate the association of lithium use in BD type I and brain levels of NAA, mI and Cho in the (anterior cingulate cortex) ACC.

Methods: 129 BD type I subjects and 79 healthy controls (HC) were submitted to a 3-Tesla brain magnetic resonance imaging scan (1H-MRS) using a PRESS ACC single voxel (8cm3) sequence.

Results: BD patients exhibited higher NAA and Cho levels compared to HC. Lithium prescription was associated with lower mI (combination + monotherapy) and higher NAA levels (monotherapy).

Conclusion: The results observed add to the knowledge about the mechanisms of action of mood stabilizers on brain metabolites during euthymia. Additionally, the observed decrease in mI levels associated with lithium monotherapy is an in vivo finding that supports the inositol-depletion hypothesis of lithium pharmacodynamics.

Keywords: Bipolar Disorder; Choline; Lithium; Myo-Inositol; N-Acetylaspartate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimanic Agents / pharmacology*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / drug therapy*
  • Brain / enzymology
  • Brain Chemistry
  • Choline / analysis
  • Cyclothymic Disorder / diagnostic imaging
  • Cyclothymic Disorder / drug therapy*
  • Female
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism
  • Humans
  • Inositol / analysis
  • Lithium Compounds / pharmacology*
  • Male
  • Middle Aged
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Treatment Outcome

Substances

  • Antimanic Agents
  • Lithium Compounds
  • Aspartic Acid
  • Inositol
  • N-acetylaspartate
  • Choline