Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia Bernardo M. Pardo a, b, ⁎, Maite Garolera c, d , Mar Ariza a, e , Deborah Pareto f , Manel Salamero g , Vicenç Valles d , Luis Delgado d , Joan Alberni d a Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain b Department of Mental Health, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Spain c Neuropsychological Unit, Hospital de Terrassa-Consorci Sanitari de Terrassa, Terrassa, Spain d Department of Mental Health, Hospital de Terrassa-Consorci Sanitari de Terrassa, Terrassa, Spain e Institute for Brain, Cognition and Behaviour (IR3C), Barcelona, Spain f Networking Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain g Department of Clinical Psychology, Hospital Clinic of Barcelona, Barcelona, Spain abstract article info Article history: Received 12 December 2010 Received in revised form 2 June 2011 Accepted 3 June 2011 Keywords: Cognition Functional neuroimaging Cerebral blood flow Second-generation antipsychotics The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction It has been observed that many persons suffering from schizo- phrenia are poorly adjusted socially even when they are free of psychotic symptoms (Bobes et al., 2009; Lipkovich et al., 2009). Several studies (Prouteau and Doron, 2008; Williams et al., 2008; Aubin et al., 2009; Rocca et al., 2009; Lysaker et al., 2010) have shown that the adaptive function of these patients correlates with cognitive performance in several areas, especially executive functions, verbal learning, memory, sustained attention, instrumental skills and the ability to solve problems. These functions are commonly affected in patients with schizophrenic disorder. Therefore, the ability of new treatments to improve overall neuropsychological performance is critical. The beneficial effects of second-generation neuroleptics on cognitive flexibility function are controversial. There are studies supporting these effects (Keefe et al., 2006; Gurpegui et al., 2007; O'Grada and Dinan, 2007; Davidson et al., 2009), and other studies that report a lack of evidence in this regard (Akdede et al., 2006; Goldberg et al., 2007; Gonzalez-Blanch et al., 2008; Houthoofd et al., 2008). Numerous studies have examined the relationships between the above-mentioned cognitive deficits in patients with schizophrenic disorder and certain dysfunctional patterns of brain activation, especially in the prefrontal areas (Salgado-Pineda et al., 2004; de la Torre et al., 2005; Salgado-Pineda et al., 2007; Minzenberg et al., 2009; Camchong et al., 2011). It is likely that the beneficial effects of new drugs on these cognitive functions would be accompanied by an improvement of these dysfunctional patterns. However, we again found a lack of consistency in the results of studies that have examined this hypothesis (Zavitsanou and Huang, 2002; Jones et al., 2004; Snitz et al., 2005; Brewer et al., 2007; Tislerova et al., 2008; Keedy et al., 2009; Lahti et al., 2009; Schlagenhauf et al., 2010). To study the changes in cognitive function in patients with schizophrenic disorder that are induced by neuroleptic treatment, along with the correlations with brain activity, the ideal methodological conditions require the use of longitudinal designs and neuroactivation conditions. The ideal group of experimental subjects would be suffering Psychiatry Research: Neuroimaging 194 (2011) 205–211 ⁎ Corresponding author at: Parc Sanitari Sant Joan de Deu. Hospital de Sant Boi - Area de Salut Mental, Antoni Pujadas 42, 08830 Sant Boi de Llobregat, Barcelona, Spain. Tel.: +34 93 6406350x2267; fax: +34 93 6002653. E-mail address: bmpardo@pssjd.org (B.M. Pardo). 0925-4927/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2011.06.001 Contents lists available at ScienceDirect Psychiatry Research: Neuroimaging journal homepage: www.elsevier.com/locate/psychresns