A Longitudinal (6-week) 3T 1H-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression

The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium׳s effects on ACC metabolites using 1H-MRS, as well as its association with clinical improvement in bipolar depression. This 1H-MRS (TE=35 ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium׳s therapeutic effects in BD.