Proton magnetic resonance spectroscopy of prefrontal white matter in psychotropic naïve children and adolescents with obsessive–compulsive disorder Alexander Mark Weber a , Noam Soreni a,b,c,j,n , Jeffrey A. Stanley i , Alessia Greco b,c , Sandra Mendlowitz h , Peter Szatmari b,c , Russell Schachar h , Katharina Mannasis h , Paulo Pires b,c , Richard Swinson b,c,j , Michael D. Noseworthy a,d,e,f,g a School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada b Department of Psychiatry and Behavioural Neuroscience, Hamilton, ON, Canada c Offord Centre for Child Studies, McMaster University, McMaster Children's Hospital, Hamilton, ON, Canada d Electrical & Computer Engineering, McMaster University, Hamilton, ON, Canada e Medical Physics & Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada f Diagnostic Imaging, St. Joseph's Healthcare, Hamilton, ON, Canada g Department of Radiology, McMaster University, Hamilton, ON, Canada h Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada i Department of Psychiatry and Behavioral Neurosciences, Wayne State University, School of Medicine, Detroit, MI, USA j Anxiety Treatment and Research Center, St. Joseph's Healthcare, Hamilton, ON, Canada article info Article history: Received 12 December 2012 Received in revised form 13 December 2013 Accepted 7 February 2014 Available online 17 February 2014 Keywords: 1 H-MRS OCD Pediatric White matter Psychotropic-naïve Brain abstract Obsessive–compulsive disorder (OCD) has a typical onset during childhood or adolescence. Although recent in-vivo proton magnetic resonance spectroscopy ( 1 H-MRS) studies report gray matter metabolite abnormalities in children and adolescents with OCD, there are no existing 1 H-MRS studies that measure white matter (WM) metabolite levels in this population. In the present study, we measured metabolite levels in the left and right prefrontal WM (LPFWM and RPFWM, respectively) of psychotropic-naïve children and adolescents with OCD (LPFWM: N¼15, mean age 13.3 72.4 years; right RPFWM: N ¼14, mean age 13.0 72.3 years) and healthy controls (LPFWM: N¼17, mean age 11.8 72.7 years; RPFWM: N¼18, mean age 12.2 72.8 years). Spectra were acquired using a 3T single voxel PRESS sequence (1.5 Â 2.0 Â 2.0 cm 3 ). When age and sex effects were controlled, OCD patients had higher levels of RPFWM choline and N-acetyl-aspartate (NAA). In addition, RPFWM levels of NAA, creatine and myo- inositol were positively and significantly correlated with severity of OCD symptoms. In summary, this is the first published study of WM metabolite levels in children and adolescents with OCD. Our preliminary findings lend further support to the previous findings of WM abnormalities in OCD. & 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Obsessive–compulsive disorder (OCD) is a common and severe neuropsychiatric disorder, with a lifetime prevalence of 1–2.5% (Bebbington, 1998; Horwath and Weissman, 2000; Ruscio et al., 2010). The onset of OCD is usually during youth (i.e., childhood and adolescence) (Angst et al., 2004), resulting in functional impairment in home, school and social settings (Valderhaug and Ivarsson, 2005). Structural and functional neuroimaging studies of youth and adults with OCD suggest an impairment of the cortico-striatal- thalamic-cortical (CSTC) circuits (Saxena et al., 1998, 2001; Graybiel and Rauch, 2000), which include cortical and sub- cortical gray matter structures, connected through glutamatergic downstream cortico-striatal and upstream thalamo-cortical white matter (WM) projections (Carlsson, 2001; Greenamyre, 2001). A recent meta-analysis (Menzies et al., 2008) supported the association of CSTC circuitries with OCD and also implicated several other brain regions, including the limbic and paralimbic structures, connected to the CSTC circuitries by way of the anterior Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/psychresns Psychiatry Research: Neuroimaging http://dx.doi.org/10.1016/j.pscychresns.2014.02.004 0925-4927 & 2014 Elsevier Ireland Ltd. All rights reserved. n Corresponding author at: Anxiety Treatment and Research Center, St. Joseph's Healthcare, 50 Charlton Ave. East, Hamilton, Ontario, Canada. L8N 4A6. Tel.: þ1 905 522 1155x35379. E-mail address: nsoreni@sjtoes.ca (N. Soreni). Psychiatry Research: Neuroimaging 222 (2014) 67–74