Schizophrenia Research 160 (2014) 233–234
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Letter to the Editor Cortico-accumbens circuitry in schizophrenia: Merely a “reward system”? Keywords: Nucleus accumbens Schizophrenia Cannabis Reward Hallucinations Salience
Dear Editors In their recent report, Adina Fischer et al. found that the administration of either oral delta-9-tetrahydrocannabinol (THC) or smoked cannabis to patients with schizophrenia increased the resting-state functional connectivity (rs-fc) between the nucleus accumbens (NAc) and several anterior brain regions, including the ventral anterior cingulate cortex (vACC), orbitofrontal cortex (OFC), anterior prefrontal cortex (aPFC), parahippocampal cortex, and entorhinal cortex and insular cortex (Fischer et al., 2014). Based on these ﬁndings, the authors concluded that both THC and cannabis improved rs-fc in what they called the “reward system”. Connections between the NAc and anterior cortical areas are well-known to be involved in addiction and craving, most notably through mesolimbic dopaminergic projections (Koob and Volkow, 2010). However, these connections have also been implicated in many other functional (e.g., salience processing) and dysfunctional (e.g., psychosis) processes (Heinz and Schlagenhauf, 2010). According to current research, it appears that dopamine does not directly trigger positive symptoms; instead, it disrupts the processes of attention and salience, leading to a cascade of sensory integration abnormalities through false prediction errors, which characterize the erroneous beliefs and perceptions in schizophrenia (Fletcher and Frith, 2009; Howes et al., 2012). In this respect, we have recently explored differences in the rs-fc of the NAc of the following three groups of patients with schizophrenia: (1) those who experienced both visual and auditory hallucinations, (2) those who experienced only auditory hallucinations, and (3) those who did not experience hallucinations (Rolland et al., 2014). Our investigation found evidence indicating that the number of hallucinatory modalities experienced by schizophrenia patients was precisely linked to the rs-fc strength between the NAc and the midbrain ventral tegmental area (VTA), aPFC, OFC, vACC and parahippocampal cortex. The patients who were recruited for this study should not have smoked cannabis during the week prior to the MRI acquisition. Thus, Fischer et al. found that THC and smoked cannabis target the same network that involved in the occurrence of psychotic
http://dx.doi.org/10.1016/j.schres.2014.10.009 0920-9964/© 2014 Elsevier B.V. All rights reserved.
symptoms in schizophrenia. However, previous studies have also found that cannabis smoking strengthens the dopaminergic dysfunction of schizophrenia, thus increasing positive symptoms in these patients (Kuepper et al., 2010). Consequently, it is important for future investigations to fully understand if the cannabisand THC-induced increases in rs-fc between the NAc and the other aforementioned cerebral networks correspond to addiction processes (i.e., the “reward” function) or psychosis (i.e., the “salience” function). Though Fischer et al. found no global increase in the symptom severity following the cannabis or THC administration, the changes in the scores of each item of the Positive And Negative Syndrome Scale (Kay et al., 1987) were not detailed in the article, and it is thus impossible to exclude that the intensity or the diversity of some positive symptoms was not increased by cannabis or THC. Therefore, future reproductions or extensions of the investigation by Fischer et al. regarding the rs-fc of the NAc among patients with both schizophrenia and cannabis use should carefully evaluate the intensity and nature of patients' positive symptoms. Contribution Both authors have written the manuscript.
Conﬂict of interest None.
References Fischer, A.S., Whitﬁeld-Gabrieli, S., Roth, R.M., Brunette, M.F., Green, A.I., 2014. Impaired functional connectivity of brain reward circuitry in patients with schizophrenia and cannabis use disorder: effects of cannabis and THC. Schizophr. Res. http://dx.doi. org/10.1016/j.schres.2014.04.033. Fletcher, P.C., Frith, C.D., 2009. Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia. Nat. Rev. Neurosci. 10, 48–58. http://dx.doi. org/10.1038/nrn2536. Heinz, A., Schlagenhauf, F., 2010. Dopaminergic dysfunction in schizophrenia: salience attribution revisited. Schizophr. Bull. 36, 472–485. http://dx.doi.org/10.1093/schbul/ sbq031. Howes, O.D., Kambeitz, J., Kim, E., Stahl, D., Slifstein, M., Abi-Dargham, A., Kapur, S., 2012. The nature of dopamine dysfunction in schizophrenia and what this means for treatment: meta-analysis of imaging studies. Arch. Gen. Psychiatry http://dx.doi.org/10.1001/ archgenpsychiatry.2012.169. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 261–276. Koob, G.F., Volkow, N.D., 2010. Neurocircuitry of addiction. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 35, 217–238. http://dx.doi.org/10.1038/npp. 2009.110. Kuepper, R., Morrison, P.D., van Os, J., Murray, R.M., Kenis, G., Henquet, C., 2010. Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of ﬁndings across disciplines. Schizophr. Res. 121, 107–117. http://dx.doi.org/10. 1016/j.schres.2010.05.031. Rolland, B., Amad, A., Poulet, E., Bordet, R., Vignaud, A., Bation, R., Delmaire, C., Thomas, P., Cottencin, O., Jardri, R., 2014. Resting-state functional connectivity of the nucleus accumbens in auditory and visual hallucinations in schizophrenia. Schizophr. Bull. http://dx.doi.org/10.1093/schbul/sbu097.
Letter to the Editor
Benjamin Rolland Department of Addiction Medicine, CHRU Lille, Lille, France Department of Pharmacology, EA1046, Univ Lille 2, Lille, France Correspondent author at: Service d'Addictologie, Hôpital Fontan 2, CHRU de Lille, CS70001, 59037 Lille Cedex, France. Tel.: +33 320 445 838; fax: +33 320 445 447. E-mail address: [email protected]
Renaud Jardri Department of Child and Adolescent Psychiatry, CHRU Lille, Lille, France SCA-Lab, PSYChiC team, Lille University, Lille, France 2 September 2014