Hippocampal 1 H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy F.G. Gilliam, MD, MPH; B.M. Maton, MD; R.C. Martin, PhD; S.M. Sawrie, PhD; R.E. Faught, MD; J.W. Hugg, PhD; M. Viikinsalo, BS; and R.I. Kuzniecky, MD Abstract—Objective: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. Methods: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated 1 H magnetic resonance spectroscopic imaging ( 1 H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. Results: The extent of hippocampal 1 H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value  0.001), but other clinical factors did not. Conclusion: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability. NEUROLOGY 2007;68:364–368 Depression is a common comorbid condition in many neurologic disorders and appears to have an in- creased prevalence in community 1 and tertiary 2 sam- ples of persons with epilepsy. Depression contributes to poor health outcomes 2-5 and increased health care costs in epilepsy. 6,7 Although few studies have evalu- ated the association of depression with specific epi- lepsy syndromes, temporal lobe epilepsy is frequently implicated. 3 Involvement of the limbic 8-10 or ventral prefrontal 11,12 structures is a possible ex- planation of the increased prevalence of depression in temporal lobe epilepsy, but the influence of re- gional brain dysfunction as opposed to social and psychological factors is not known. 13 To evaluate the contribution of potential neuronal and psychosocial factors to depression in temporal lobe epilepsy, we determined the association of severity of depression symptoms with the extent of 1 H magnetic resonance spectroscopic imaging ( 1 H-MRSI) hippocampal ab- normalities, clinical variables, and self-perceived disability. Methods. Patients. We studied a sample of adult patients who met the following criteria: 1) having had a diagnosis of temporal lobe epilepsy confirmed by recorded seizures during video/EEG monitoring, 2) capable of completing self-report questionnaires, 3) agreeing with and signing an informed consent document ap- proved by our institutional review board (IRB), and 6) age 17 years or older. This lower age limit was used because the mood and health outcome variables had not been tested for reliability and validity in children and adolescents. Study questionnaires were administered by the study coordinator (M.V.) and were com- pleted by patients in a private setting, usually in the outpatient neurology clinic. Magnetic resonance spectroscopic imaging acquisition and analysis. All adult patients undergoing presurgical evaluation for refractory temporal lobe epilepsy at the University of Alabama at Birmingham during the study period were offered 1 H-MRSI through a National Institute of Neurologic Disorders and Stroke– supported protocol (NS033919). 14 Details of the imaging protocol and examples of subject 1 H-MRSI maps can be found in earlier publications. 14-17 The subjects in the current study were a conve- nience sample who agreed to undergo 1 H-MRSI and were able to obtain transportation at a time when the MR scanner was avail- able. Briefly, all studies were performed in the interictal state, using a 4.1-T whole-body imaging/spectroscopy system and a quadrature-driven, tunable, matchable head coil. Sagittal and transverse scout images were acquired using inversion recovery gradient echo sequence (TR [repetition time]/inversion recovery time [TIR]/echo time [TE] 2,500/1,000/15). The transverse im- ages were angulated to be parallel to the long axis of the hip- pocampi and used to select a rectangular region of interest (ROI) in the temporal lobes that included both hippocampal regions. Water- and lipid-suppressed spectroscopic images were acquired using a TR of 2,000, TE of 50 msec, a field of view of 240  240 mm, and 32  32 phase encodes with a slice thick- ness of 1 cm. Nominal voxed size was 0.5 cc. Scanning was not performed in the immediate postictal state. Data from the subjects’ 1 H-MRSI were analyzed by a MR phys- icist (J.H.) without knowledge of the clinical, mood, or EEG data. The creatine (Cr)/N-acetylaspartate (NAA) metabolite ratio maps were produced by automated NMR1 (Tripos, Syracuse, NY) fitting of spectra. The normal hippocampal Cr/NAA value acquired in 20 normal healthy volunteers was 0.72  0.14. Approximately five to six pixels were placed along the length of the hippocampus and two to three across the width. We compared the Cr/NAA ratio in From the Department of Neurology (F.G.G.), Columbia University, New York, NY; Department of Neurology (R.C.M., S.M.S., R.E.F., M.V.), University of Alabama at Birmingham; Department of Neurology (R.I.K.), New York University, New York, NY; GE Global Research Center (J.W.H.), Niskayuna, NY; The Brain Institute (B.M.M.), Miami Children’s Hospital, Miami, FL. Supported by National Institutes of Health grants NS01794, NS033919, NS40808, NS047551, and a grant from the Epilepsy Foundation of America. Disclosure: The authors report no conflicts of interest. Received December 12, 2005. Accepted in final form October 9, 2006. Address correspondence and reprint requests to Dr. Frank G. Gilliam, The Neurological Institute, Columbia University, New York, NY 10032; e-mail: fgilliam@neruo.columbia.edu 364 Copyright © 2007 by AAN Enterprises, Inc.