1 H Magnetic resonance spectroscopy study of dorsolateral prefrontal cortex in unipolar mood disorder patients Paolo Brambilla a,b,c , Jeffrey A. Stanley d , Mark A. Nicoletti a , Roberto B. Sassi d,f , Alan G. Mallinger d,e , Ellen Frank d , David J. Kupfer d , Matcheri S. Keshavan d , Jair C. Soares a,g,T a Department of Psychiatry, Division of Mood and Anxiety Disorders, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA b Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine School of Medicine, Udine, Italy c Advanced Biotechnology Center, University of Genova, Genova, Italy d Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA e Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA f Department of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil g South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX, USA Received 1 June 2004; accepted 10 December 2004 Abstract Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1 H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1 H MRS examination localized to an 8-cm 3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline- containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the 0925-4927/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2004.12.001 T Corresponding author. Department of Psychiatry, Division of Mood and Anxiety Disorders, 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. E-mail address: soares@uthscsa.edu (J.C. Soares). Psychiatry Research: Neuroimaging 138 (2005) 131 – 139 www.elsevier.com/locate/psychresns