Abnormalities involving the prefrontal cortex (PFC) have long been postulated to underpin the pathophysiology of schizophrenia. Investigations of PFC integrity have focused mainly on the dorsolateral PFC (DLPFC) and abnormalities in this region have been extensively documented. However, defects in schizophrenia may extend to other prefrontal regions, including the ventromedial PFC (VMPFC), and evidence of VMPFC abnormalities comes from neuropathological, structural and functional studies. Patients with acquired brain injury to the VMPFC display profound disruption of social behaviour and poor judgment in their personal lives. The Iowa Gambling Task (IGT) was developed to assess decision-making in these neurological cases : it presents a series of 100 choices from four card decks that differ in the distribution of rewarding and punishing outcomes. Whilst healthy volunteers gradually develop a preference for the two "safe" decks over the course of the task, patients with VMPFC lesions maintain a preference for the two "risky" decks which are associated with high reinforcement in the short term, but significant long-term debt. Interestingly, damage to VMPFC may cause both poor performance on the IGT and lack of insight concerning the acquired personality modification. Recently, our group reported a trait-related decisionmaking impairment in the three phases of bipolar disorder. In a PET study, VMPFC dysfunction was shown in bipolar manic patients impaired on a decision-making task and an association between decision-making cognition and lack of insight was described in mania. A quantitative association between grey matter volume of VMPFC and memory impairment was previously reported in schizophrenia. Research suggests that lack of insight is a prevalent feature in schizophrenia patients, like auditory hallucinations, paranoid or bizarre delusions, and disorganized speech and thinking. Because schizophrenia is associated with significant social or occupational dysfunction, previous research assessed decision-making function but indicates conflicting results. Thirteen studies have reported impaired IGT performance in patients with schizophrenia and, in seven reports, no significant differences in IGT performance between patient and healthy control groups were found. Those discrepancies may relate to multiple factors. First, most of the studies included small sample size and negative findings may be due to the large variance of net scores. Second, as suggested by Rodríguez-Sánchez et al., there is a wide disparity in performance by control subjects across studies. Third, intelligence quotient (IQ) score and level of education may be correlated with IGT performance, which may explain IGT performance differences in studies that did not control for educational or IQ score. Fourth, only two studies have systematically controlled for substance use disorder, a potential confounder. Fifth, only two studies assessed the impact of antipsychotic (AP) class on performance. Sixth, to our knowledge, no study assessed the impact of AP dosage on decision-making ability, while AP dose-reduction and dopamine increase, might lead to improvements, in cognitive functions in schizophrenia and in IGT performance in bipolar disorder, respectively. Finally, discrepancies between studies may be related to the heterogeneity of diagnostic groups. Two of the negative studies included schizophrenia and schizoaffective disorder while positive studies have generally included only patients with schizophrenia. Nevertheless, some studies that included only patients with schizophrenia failed to find differences between groups. Thus, further research should assess decision-making in schizophrenia by testing a large group of patients with homogeneity of diagnostic, in comparison with a large group of control subjects. Authors should control for IQ or level of education, substance use disorder and smoking status. While it is now accepted that DLPFC defects in schizophrenia may extend to VMPFC, future investigations should test for an association between memory, insight ability and IGT performance and assess the impact of antipsychotic dosage upon performance.
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Oct 1, 2012
M Spangaro + 7
Open Access