Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings Stéphane Potvin a,b, ⁎, Ovidiu Lungu b,c,d , Olivier Lipp b,e , Pierre Lalonde b,e , Vessela Zaharieva a , Emmanuel Stip b,f , Jean-Pierre Melun b,e , Adrianna Mendrek a,g a Centre de recherche de l'Institut Universitaire en Santé Mentale de Montréal, Montréal, Canada b Department of Psychiatry, University of Montreal, Montreal, Canada c Institut de Gériatrie de l'Université de Montréal, Montreal, Canada d Centre for Research in Aging, Donald Berman Maimonides Geriatric Centre, Montreal, Canada e Institut Universitaire en Santé Mentale de Montréal, Montreal, Canada f Centre Hospitalier de l'Université de Montréal, Montreal, Canada g Department of Psychology, Bishop's University, Lennoxville, Canada abstract article info Article history: Received 11 January 2016 Received in revised form 7 March 2016 Accepted 10 March 2016 Available online xxxx Background: Highly prevalent in schizophrenia, tobacco smoking substantially increases the risk of cardiac- related death. Compared to the general population, tobacco smoking cessation rates are lower in schizophrenia. Unfortunately, the reasons for these low cessation rates remain poorly understood. Recently, it has been shown that tobacco cravings are increased in schizophrenia smokers compared to smokers with no comorbid psychiatric disorder. In view of these results, we sought to examine – for the first time – the neurophysiologic responses elic- ited by cigarette cues in schizophrenia smokers. We hypothesized that cigarettes cues would elicit increased ac- tivations in brain regions involved in drug cravings in schizophrenia smokers relative to control smokers. Methods: Smokers with (n = 18) and without (n = 24) schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging (fMRI) while viewing appetitive cigarette images. Results: Schizophrenia smokers and smokers with no psychiatric comorbidity did not differ in subjective cravings in response to appetitive smoking cues. However, in schizophrenia smokers relative to control smokers, we found that appetitive cigarette cues triggered increased activations of the bilateral ventro-medial prefrontal cor- tex, a core region of the brain reward system. Moreover, a negative correlation was observed between cigarette cravings and activations of the right ventro-medial prefrontal cortex in schizophrenia smokers. Discussion: The current results highlight a key role of the brain reward system in cigarette craving in schizophre- nia, and suggest that the neurophysiologic mechanisms involved in the regulation of cue-induced cigarette crav- ing are impaired in this population. © 2016 Elsevier B.V. All rights reserved. Keywords: Schizophrenia Cigarette Cravings Brain reward system Functional magnetic resonance imaging 1. Introduction In relative numbers, a meta-analysis of worldwide studies has shown that there is a 3- to 6-fold increase of smoking prevalence (cur- rent, lifetime) in schizophrenia (de Leon and Diaz, 2005). In schizophre- nia, cigarette smoking has dramatic health consequences. For individuals aged between 35 and 54 years old, it has been estimated that the odds of cardiac-related death were increased by 12-fold in schizophrenia smokers relative to schizophrenia non-smokers (Kelly et al., 2011). Unfortunately, smoking cessation rates are significantly lower in persons with schizophrenia, compared to people with no co- morbid psychiatric disorders (Aubin et al., 2012). Despite that tobacco smoking is highly prevalent and has deleterious effects in schizophre- nia, the mechanisms motivating persons to smoke are insufficiently understood. Two major hypotheses have been advanced to explain smoking mo- tivation in schizophrenia. The self-medication hypothesis proposes that persons with schizophrenia smoke cigarettes in order to relieve their psychiatric symptoms (e.g. anxiety & dysphoria), to relieve their cogni- tive deficits, to attenuate antipsychotics' side effects and/or to handle nicotine withdrawal symptoms (DiFranza et al., 2012; Esterberg and Compton, 2005; Winterer, 2010). In support of this hypothesis, several controlled trials have shown that the acute administration of nicotine (the main psychoactive agent of tobacco) to persons with schizophrenia improves some of their frontal cognitive deficits, including attention and working memory deficits (Barr et al., 2008). However, some studies have failed to confirm these findings (Hahn et al., 2013; Krishnadas et al., 2012). In addition, the self-medication hypothesis has been Schizophrenia Research xxx (2016) xxx–xxx ⁎ Corresponding author at: Centre de recherche de l'Institut Universitaire en Santé Mentale de Montréal, 7331 Hochelaga, Montreal H1N 3V2, Canada. E-mail address: stephane.potvin@umontreal.ca (S. Potvin). SCHRES-06757; No of Pages 7 http://dx.doi.org/10.1016/j.schres.2016.03.011 0920-9964/© 2016 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Please cite this article as: Potvin, S., et al., Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.03.011