1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration

Abstract

The mechanism of action of lithium is still largely unknown. However, recent animal and human studies suggested the possible neuroprotective effects of this medication. In particular, a recent magnetic resonance spectroscopy (MRS) study showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity/functioning, in both bipolar patients and normal controls after 4 weeks of lithium administration. We investigated the effects of lithium on NAA levels in a sample of healthy individuals using in vivo 1 H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time 1 H-MRS measurements of 8 cm 3 single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals (mean age7SD ¼ 25.079.8 years; six males). After lithium administration, no significant differences in NAA, phosphocreatine plus creatine, glycerophosphocholine plus phosphocholine (or choline-containing molecules), and myo-inositol absolute levels or ratios were found in DLPFC (paired t-tests, p40.05). Contrary to prior MRS reports in bipolar patients, we found that lithium administration did not significantly increase NAA levels in the DLPFC of healthy individuals. Future longitudinal studies will be needed to further investigate whether chronic lithium treatment increases NAA levels in other brain regions in healthy individuals, and whether it promotes changes in these levels in specific brain regions in bipolar patients.

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

“…The difference in our study vs the Chang study is that the increase in our cohort was only identified in those subjects with low levels at baseline. The baseline NAA by remit status interaction is as well consistent with the hypothesis originally proposed by Brambilla et al, (2004) whereby treatment-associated increases in NAA may only be identified in NAA deficient disease states. In their study, lithium administration to healthy controls was not associated with an increase in NAA.…”

Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder

“…10 However, a recent clinical study on control subjects taking chronic lithium showed no changes in NAA. 77 It remains unclear whether the NAA increase after lithium treatment is a diseasespecific effect, or an effect on baseline brain chemistry. In our study, neither chronic lithium nor chronic valproate treatment increased NAA levels in the rat brain.…”

Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis

“…[8][9][10][11][12][13] Smaller hippocampal volumes are among the most replicated neuroimaging findings in patients with major depressive disorder compared with healthy controls.…”