Volume reductions in frontopolar and left perisylvian cortices in methamphetamine induced psychosis Yuta Aoki a, b , Lina Orikabe a , Yoichiro Takayanagi b , Noriaki Yahata a , Yuriko Mozue b , Yasuhiko Sudo b , Tatsuji Ishii c , Masanari Itokawa d , Michio Suzuki e , Masayoshi Kurachi e , Yuji Okazaki b , Kiyoto Kasai a , Hidenori Yamasue a, ⁎ a Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan b Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, 2-1-1 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan c Department of Radiology, Tokyo Metropolitan Matsuzawa Hospital, 2-1-1 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan d Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan e Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, 2630 Sugitani, Toyama 930-0194, Japan abstract article info Article history: Received 28 November 2012 Received in revised form 21 April 2013 Accepted 22 April 2013 Available online xxxx Keywords: Brain Brodmann area (BA) 10 Frontal pole Human Stimulant Substance use Consumption of methamphetamine disturbs dopaminergic transmission and sometimes provokes schizophrenia- like-psychosis, named methamphetamine-associated psychosis (MAP). While previous studies have repeatedly reported regional volume reductions in the frontal and temporal areas as neuroanatomical substrates for psychotic symptoms, no study has examined whether such neuroanatomical substrates exist or not in patients with MAP. Magnetic resonance images obtained from twenty patients with MAP and 20 demographically-matched healthy controls (HC) were processed for voxel-based morphometry (VBM) using Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra. An analysis of covariance model was adopted to identify volume differences be- tween subjects with MAP and HC, treating intracranial volume as a confounding covariate. The VBM analyses showed significant gray matter volume reductions in the left perisylvian structures, such as the posterior inferior frontal gyrus and the anterior superior temporal gyrus, and the frontopolar cortices, including its dorsomedial, ven- tromedial, dorsolateral, and ventrolateral portions, and white matter volume reduction in the orbitofrontal area in the patients with MAP compared with the HC subjects. The smaller regional gray matter volume in the medial por- tion of the frontopolar cortex was significantly correlated with the severe positive symptoms in the individuals with MAP. The volume reductions in the left perisylvian structure suggest that patients with MAP have a similar patho- physiology to schizophrenia, whereas those in the frontopolar cortices and orbitofrontal area suggest an association with antisocial traits or vulnerability to substance dependence. © 2013 Elsevier B.V. All rights reserved. 1. Introduction In Japan, it has been recognized in years that administration of methamphetamine (METH) can cause persistent psychosis, including visual and auditory hallucinations and delusions, in healthy subjects without preexisting psychiatric problems. This process was termed METH associated psychosis (MAP) (Ellinwood, 1968; Rylander, 1972; Ellinwood et al., 1973; Iwanami et al., 1991; Sato et al., 1992; McKetin et al., 2006; Matsuzawa et al., 2007; Kishimoto et al., 2008). In the USA, it has been recognized that stimulants can cause initiation and maintenance of schizophrenia-like psychosis (Flaum and Schultz, 1996). A recently published population-based cohort study in California demonstrated that consumption of METH signifi- cantly increased the risk of developing schizophrenia-like psychosis (Callaghan et al., 2012). Because of the recent rapid expansion of illegal usage of METH in the USA (Substance Abuse and Mental Health Services Administration office of applied studies., 2012), MAP is now of particular interest in the clinical (Grelotti et al., 2010) and research settings (Rounsaville, 2007). Neuroimaging studies have repeatedly reported that enhanced do- paminergic transmission is the potential underlying pathophysiology of MAP (Sekine et al., 2001, 2003; Grant et al., 2012), and dopamine an- tagonists effectively attenuate MAP (reviewed in Grant et al., 2012). In addition, genetic studies have also provided evidence that MAP and schizophrenia have many genetic vulnerabilities in common (reviewed in Grant et al., 2012). These clinical and genetic similarities between MAP and schizophrenia have implied that MAP may be a human phar- maceutical model of schizophrenia (Grant et al., 2012). Moreover, they have provoked debate as to whether persistent MAP is distinct from schizophrenia, and hence requires a separate diagnostic classification (Rounsaville, 2007; Callaghan et al., 2012). Although both patients with MAP and those with schizophrenia experience delusions and hallucinations, patients with MAP tend to Schizophrenia Research xxx (2013) xxx–xxx ⁎ Corresponding author. Tel.: +81 3 5800 9263; fax: +81 3 5800 6894. E-mail address: yamasue-tky@umin.ac.jp (H. Yamasue). SCHRES-05405; No of Pages 7 0920-9964/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.schres.2013.04.029 Contents lists available at SciVerse ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Please cite this article as: Aoki, Y., et al., Volume reductions in frontopolar and left perisylvian cortices in methamphetamine induced psychosis, Schizophr. Res. (2013), http://dx.doi.org/10.1016/j.schres.2013.04.029