Dose-dependent frontal hypometabolism on FDG-PET in methamphetamine abusers Yang-Tae Kim a , Sang-Woo Lee b, * , Do-Hoon Kwon a , Ji-Hyoung Seo b , Byeong-Cheol Ahn b , Jaetae Lee b a Department of Psychiatry, Bugok National Hospital, Republic of Korea b Department of Nuclear Medicine, Kyungpook National University Hospital, Samduk 2-Ga 50, Daegu 700-721, Republic of Korea article info Article history: Received 26 June 2008 Received in revised form 23 March 2009 Accepted 23 March 2009 Keywords: Methamphetamine FDG-PET Wisconsin card sorting test abstract Objective: Although a lot of evidence from neuropsychological and neuroimaging studies supports the view that patients with substance dependence have abnormalities in the prefrontal cortex, functional deficits in the prefrontal cortex have not been fully investigated in methamphetamine (MA) dependent patients. This study was prepared to examine whether MA abusers have cerebral metabolic abnormalities and executive dysfunction. Method: Twenty-four abstinent MA dependent patients and 21 age-matched control subjects underwent resting brain FDG-PET and completed computerized versions of the Wisconsin card sorting test (WCST). Resting brain PET images were obtained 30 min after an intravenous injection of 370 MBq of 18 F-FDG. Sig- nificant differences in glucose metabolism were estimated for every voxel using t-statistics on SPM2 implemented in Matlab. Results: Resting brain FDG-PET revealed significant hypometabolism in the left inferior frontal white matter (Talairach coordinates (x, y, z): À34, 7, 31) in MA dependent patients compared to the control sub- jects (corrected p = 0.001, peak Z = 5.37, voxel number 201). The nearest gray matter region was the left inferior frontal cortex (Brodmann area 9). There were negative correlations between the relative regional cerebral metabolism for glucose (rCMRglc) in the left inferior frontal white matter and the total cumula- tive dose of MA (r = À0.57, p < 0.01). MA dependent patients completed significantly fewer categories (3.8 ± 2.2) and made more perseveration errors (21.3 ± 11.8) and total errors (43.5 ± 19.5) on the WCST when compared to the control subjects (p < 0.01). Conclusions: These data suggest that MA dependent patients have dose-dependent frontal hypometabo- lism and frontal executive dysfunction. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Drug addiction is a chronically relapsing disorder that is mani- fested by preoccupation–anticipation, binge-intoxication, and the withdrawal-negative affect (Koob and Le Moal, 2001). As the addic- tion cycle makes progress, drug abusers are characterized by com- pulsive use and loss of control over drug-taking, which become more reflexive and much less reflective consequently. This behav- ior could explain the dysfunction in attention and execution as well as impaired inhibitory control, which is related to reduced activity in the prefrontal cortex (Goldstein and Volkow, 2002; Baler and Volkow, 2006). Recently, there is mounting evidence from neuroimaging stud- ies to support the view that drug abusers have various kinds of abnormalities in frontal cortex. The frontal areas are vulnerable to the neurotoxic effects of addictive drugs, since the mesolimbic dopamine pathway projects to terminal fields in the prefrontal cor- tex as well as the nucleus accumbens. For instance, loss of frontal lobe volume has been demonstrated in patients with cocaine (Liu et al., 1998; Franklin et al., 2002), alcohol (Jernigan et al., 1991a, 1991b; Pfefferbaum et al., 1997), and heroin dependence (Liu et al., 1998). In drug abusers, the orbitofrontal cortex and the ante- rior cingulate gyrus are activated during preoccupation–anticipa- tion and binge-intoxication, whereas they are deactivated during the withdrawal-negative affect (Goldstein and Volkow, 2002). There is also a growing body of evidence suggesting that the frontal cortex is also dysfunctional in methamphetamine (MA) abusers. Using magnetic resonance spectroscopy, several studies demonstrated reduced concentration of N-acetylaspartate in the basal ganglia and frontal white matter (Ernst et al., 2000) and low- er N-acetyl-aspartate/creatine in the anterior cingulum (Nordahl et al., 2002) in MA abusers. Decreased dopamine transporter den- sity in the orbitofrontal cortex and the dorsolateral prefrontal cor- tex has been previously reported in MA abusers (Sekine et al., 2003). Paulus et al. (2002, 2003) demonstrated less activation of both the orbitofrontal and dorsolateral prefrontal cortices during decision-making tasks in MA abusers using functional magnetic resonance imaging. Recent neuroimaging studies revealed lower regional cerebral glucose metabolism in the right superior frontal 0022-3956/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2009.03.011 * Corresponding author. Tel.: +82 53 420 5585; fax: +82 53 422 0864. E-mail address: swleenm@knu.ac.kr (S.-W. Lee). Journal of Psychiatric Research 43 (2009) 1166–1170 Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/jpsychires