Anterior cingulate cortex neuro-metabolic changes underlying lithium-induced euthymia in bipolar depression: A longitudinal 1H-MRS study

Eur Neuropsychopharmacol. 2021 Aug:49:93-100. doi: 10.1016/j.euroneuro.2021.03.020. Epub 2021 Apr 18.

Abstract

The diagnosis and treatment of bipolar depression (BDep) poses complex clinical challenges for psychiatry. Proton magnetic resonance spectroscopy (1H-MRS) is a useful imaging tool for investigating in vivo levels of brain neuro-metabolites, critical to understanding the process of mood dysregulation in Bipolar Disorder. Few studies have evaluated longitudinal clinical outcomes in BDep associated with 1H-MRS metabolic changes. This study aimed to longitudinally assess brain 1H-MRS metabolites in the anterior cingulate cortex (ACC) correlated with improvement in depression (from BDep to euthymia) after lithium treatment in BDep patients versus matched healthy controls (HC). Twenty-eight medication-free BDep patients and 28 HC, matched for age and gender, were included in this study. All subjects were submitted to a 3-Tesla brain 1H-MRS scan in the ACC using a single-voxel (8cm3) PRESS sequence at baseline. At follow-up (6 weeks), 14 BDep patients repeated the exam in euthymia. Patients with current BDep had higher baseline Myo-inositol/Cr (mI/Cr) and Choline/Cr (Cho/Cr) compared to HC. After six weeks, mI/Cr or Cho/Cr levels in subjects that achieved euthymia no longer differed to levels in HC, while high Cho/Cr levels persisted in non-responders . Elevated ACC mI/Cr and Cho/Cr in BDep might indicate increased abnormal membrane phospholipid metabolism and phosphatidylinositol (PI) cycle activity. Return of mI/Cr and Cho/Cr to normal levels after lithium-induced euthymia suggests a critical regulatory effect of lithium targeting the PI cycle involved in mood regulation.

Keywords: Anterior cingulate; Bipolar disorder; Choline; Depression; Myo-inositol; Proton spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / metabolism
  • Bipolar Disorder* / diagnostic imaging
  • Bipolar Disorder* / drug therapy
  • Brain / metabolism
  • Choline / metabolism
  • Choline / pharmacology
  • Choline / therapeutic use
  • Creatine / metabolism
  • Gyrus Cinguli / metabolism
  • Humans
  • Inositol / metabolism
  • Lithium / therapeutic use
  • Proton Magnetic Resonance Spectroscopy / methods

Substances

  • Aspartic Acid
  • Inositol
  • Lithium
  • Creatine
  • Choline