1H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients

Brambilla, Paolo; Stanley, Jeffrey A.; Nicoletti, Mark A.; Sassi, Roberto B.; Mallinger, Alan G.; Frank, Ellen; Kupfer, David; Keshavan, Matcheri S.; Soares, Jair C.

doi:10.1016/j.jad.2004.12.008

« Previous Next »Journal of Affective Disorders
Volume 86, Issue 1 , Pages 61-67, May 2005

¹H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients

Paolo Brambilla
- Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine School of Medicine, Udine, Italy
- Advanced Biotechnology Center, University of Genova, Genova, Italy
Jeffrey A. Stanley
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Mark A. Nicoletti
- Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Roberto B. Sassi
- Advanced Biotechnology Center, University of Genova, Genova, Italy
- Department of Psychiatry, Institute of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
- Department of Psychiatry, Harvard Medical School, Boston, USA
Alan G. Mallinger
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Ellen Frank
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
David Kupfer
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Matcheri S. Keshavan
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Jair C. Soares
- Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Department of Radiology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA
- South Texas Veterans Health Care System, San Antonio, TX, USA
- Corresponding author. Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Tel.: +1 210 5675492; fax: +1 210 5673759.

Received 6 October 2004; accepted 10 December 2004.

Abstract

Background

Magnetic resonance spectroscopy studies (MRS) reported abnormally low levels of N-acetylaspartate (NAA, a marker of neuronal integrity) in dorsolateral prefrontal cortex (DLPFC) of adult bipolar patients, suggesting possible neuronal dysfunction. Furthermore, recent MRS reports suggested possible lithium-induced increase in NAA levels in bipolar patients. We examined with in vivo ¹H MRS NAA levels in the DLPFC of adult bipolar patients.

Methods

Ten DSM-IV bipolar disorder patients (6 lithium-treated, 4 drug-free) and 32 healthy controls underwent a short echo-time ¹H MRS session, which localized an 8 cm³ single-voxel in the left DLPFC using a STEAM sequence.

Results

No significant differences between the two groups were found for NAA, choline-containing molecules (GPC+PC), or phosphocreatine plus creatine (PCr+Cr) (Student t-test, p>0.05). Nonetheless, NAA/PCr+Cr ratios were significantly increased in lithium-treated bipolar subjects compared to unmedicated patients and healthy controls (Mann–Whitney U-test, p<0.05).

Limitations

Relatively small sample size may have reduced the statistical power of our analyses and the utilization of a single-voxel approach did not allow for the examination of other cortical brain areas.

Conclusions

This study did not find abnormally reduced levels of NAA in left DLPFC of adult bipolar patients, in a sample of patients who were mostly on medications. However, elevated NAA/PCr+Cr ratios were shown in lithium-treated bipolar patients. Longitudinal ¹H MRS studies should further examine NAA levels in prefrontal cortex regions in untreated bipolar patients before and after mood stabilizing treatment.

Keywords: Neuroimaging, Affective disorder, Mood disorder, NAA, Lithium