1. ¹Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
2. ²Section of Psychiatry, Department of Pathology and Experimental and Clinical Medicine, University of Udine School of Medicine, Udine, Italy
3. ³Advanced Biotechnology Center, University of Genova, Genova, Italy
4. ⁴Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
5. ⁵Department of Psychiatry, University of Sao Paulo School of Medicine, Brazil
6. ⁶Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
7. ⁷Department of Radiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
8. ⁸South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX, USA

Correspondence: Dr JC Soares, Division of Mood and Anxiety Disorders, Department of Psychiatry (MC 7792), The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Tel: +1 210 567 5492; Fax: +1 210 567 3759; E-mail: soares@uthscsa.edu

Received 13 November 2003; Revised 3 June 2004; Accepted 3 June 2004; Published online 14 July 2004.

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 ¹H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time ¹H-MRS measurements of 8 cm³ single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals (mean ageSD=25.09.8 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, p>0.05). 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.