Iowa Gambling Task in schizophrenia: A review and new data in patients with schizophrenia and co-occurring cannabis use disorders

Abstract

Background

We reviewed previous studies comparing schizophrenia patients and healthy subjects for performance on the Iowa Gambling Task (IGT) (a laboratory task designed to measure emotion-based decision-making), and found mixed results. We hypothesize that deficits in IGT performance in schizophrenia may be more specifically related to concurrent substance use disorders. To test this hypothesis, we compared schizophrenia patients with (SCZ⁽⁺⁾) or without (SCZ⁽⁻⁾) cannabis use disorders, to healthy subjects, on measures of cognition and IGT performance.

Methods

A comprehensive battery of cognitive tests and the IGT were administered to three groups of subjects: (1) 13 subjects with DSM-IV diagnosis of schizophrenia and no concurrent substance use disorders (mean age: 28 ± 12 (SD); 54% males); (2) 14 subjects with schizophrenia and concurrent cannabis use disorders (mean age: 29 ± 9 (SD); 71% males); and (3) 20 healthy subjects (mean age 33 ± 10 (SD); 60% males).

Results

Compared to the healthy group, both schizophrenia groups were cognitively more impaired, and did worse on IGT performance. There were no differences between SCZ⁽⁺⁾ and SCZ⁽⁻⁾ patients on most of the cognitive tests, and IGT performance.

Conclusions

Schizophrenia patients show widespread impairments in several cognitive domains and emotion-based decision-making. These results are consistent with the evidence that schizophrenia reflects a dorsolateral and orbitofrontal/ventromedial prefrontal cortex dysfunction. More intriguing, it appears that the concurrent abuse of cannabis has no compounding effects on cognition, as well as emotion/affect-based decision-making.

Introduction

Schizophrenia is a chronic illness with deficits in emotional processing (for a review, see e.g., Tremeau, 2006). It has been proposed that emotions play a key role in decision-making (Bechara et al., 1997; Bechara, 2005). Several studies have looked at emotion-based decision-making in schizophrenia using the Iowa Gambling Task (IGT), a laboratory task specifically developed to measure decision-making in patients with lesions of the orbito-/ventromedial prefrontal cortex and with compromised emotions (Bechara et al., 1994).

Table 1 summarizes the studies comparing IGT performance between patients with schizophrenia and healthy subjects.

In several studies, patients with schizophrenia showed poor IGT performance compared to healthy subjects. Beninger et al. (2003) compared 36 patients with schizophrenia and 18 healthy controls and found that patients on atypical, but not typical, antipsychotics performed worse on the IGT compared to healthy controls. Ritter et al. (2004) compared 20 patients with schizophrenia or schizoaffective disorder with 15 healthy subjects, and found that patients chose more cards from the disadvantageous decks than the advantageous deck compared to healthy subjects. Shurman et al. (2005) compared 39 patients with schizophrenia and 10 healthy controls and found worse performance on the IGT in schizophrenia patients. In a recent study of our group, Kester et al. (2006) found worse IGT performance in 15 adolescents with schizophrenia compared to 25 normal controls. In contrast, several other studies did not find poor IGT performance in schizophrenia patients compared to healthy subjects. Wilder et al. (1998) compared 11 patients with schizophrenia and 20 healthy controls and found no significant differences between groups for IGT performance. Cavallaro et al. (2003) found no differences in IGT performance between 110 patients and 56 normal controls. Evans et al. (2005) did not find differences in IGT performance between 19 patients and 19 age- and level of education-matched normal controls. Rodríguez-Sánchez et al. (2005) compared 80 first-episode patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder and schizophreniform disorder) with 22 healthy subjects. There were no differences between groups in IGT performance although healthy subjects had a preference for “low frequency–high punishment” decks compared to patients. Thus, IGT performance is impaired in some (Beninger et al., 2003, Ritter et al., 2004, Shurman et al., 2005, Kester et al., 2006), but not all (Wilder et al., 1998, Rodríguez-Sánchez et al., 2005, Evans et al., 2005) studies.

Deficits in IGT performance in schizophrenia may be related to deficits of other areas of the prefrontal cortex. In contrast to the orbitofrontal region, which has been associated with the emotional aspects of behavior and inhibition of inappropriate behavior, the dorsolateral region is involved in working memory, language production, and executive functioning. Previous studies in schizophrenia have found cognitive deficits associated with the dorsolateral region including attention, working and declarative memory, verbal fluency, and executive function (for a review, see Williamson, 2006). The IGT may involve several dorsolateral cognitive functions such as working memory, attention, and executive function that may explain the observed deficits in schizophrenia. Some of the reviewed studies examined correlations between the IGT and tests that index parcellated aspects of dorsolateral prefrontal function. Compared to patients on typical antipsychotics, Beninger et al. (2003) found that patients on atypical antipsychotics had worse performance at the IGT but better performance on the Wisconsin Card Sorting Test (WCST — a test involving attention, working memory, and executive function). Ritter et al. (2004) found decreased performances on the IGT and WCST in schizophrenia but did not find a correlation between the two tests. Similarly, Shurman et al. (2005) reported worse performance on the IGT, WCST, and Delayed Match to Sample Task (a test assessing spatial working memory) in schizophrenia patients compared to healthy subjects but did not report a correlation between the two tests. Kester et al. (2006) reported deficits on the IGT and WCST in adolescents with schizophrenia compared to healthy adolescents, but did not find a correlation between the two tests. Thus, these studies suggest widespread deficits of prefrontal cortical functions in schizophrenia but no direct relationship between deficits of the orbitofrontal and dorsolateral prefrontal cortex.

Deficits in IGT performance in schizophrenia may be more specifically related to the co-occurrence of substance use disorders. Rates of concurrent substance use disorders are high in schizophrenia, and several studies have associated poor IGT performance with alcohol (Mazas et al., 2000, Bechara et al., 2001), psychostimulants (Bechara et al., 2001, Bolla et al., 2003), opiates (Petry et al., 1998, Mintzer and Stitzer, 2002), and marijuana (Whitlow et al., 2004, Bolla et al., 2005) abuse, as well as polysubstance abuse (Grant et al., 2000). Most drugs of abuse increase dopaminergic activity, and converging evidence from animal and human studies suggests that addiction is associated with dopaminergic dysfunction (Kalivas and Volkow, 2005). It has been suggested that individuals with addictive behaviors have reduced dopamine (D2) receptor density and dopamine release resulting in a decreased sensitivity of reward circuits to stimulation by natural rewards (Volkow et al., 2004). Further, there is evidence that emotion-based decision-making is sensitive to changes in dopaminergic activity. Czernecki et al. (2002) reported that patients with Parkinson's disease have deficits on both a reversal task and the IGT, neither of which was sensitive to l-dopa. Recently, we found that the acute administration of a branched-chain amino acid mixture (BCAA) valine, leucine, and isoleucine in healthy subjects increases prolactin levels and impairs IGT performance (Sevy et al., 2006). The acute administration of a BCAA mixture has been demonstrated to lower the plasma ratio of tyrosine + phenylalanine to BCAA and to increase prolactin levels secondary to a decrease in dopaminergic activity (Harmer et al., 2001, Gijsman et al., 2002).

As described in Table 1, several studies excluded subjects with recent use of substances (Wilder et al., 1998, Beninger et al., 2003, Ritter et al., 2004), but it was not clear whether subjects with a lifetime history of substance use disorders were excluded. Some studies did not provide information regarding the inclusion of subjects with substance use disorders (Cavallaro et al., 2003, Evans et al., 2005, Thurnbull et al., 2006). One study included patients with cocaine and alcohol use disorders, but the “healthy” subject group also included individuals using cocaine and alcohol (Ritter et al., 2004). However, the authors reported that alcohol abuse/dependence as a covariate did not significantly change the results. To date, there have been no studies that directly compared IGT performance between schizophrenia patients with and without substance use disorders. In contrast, several studies have compared schizophrenia patients with and without substance use disorders with regard to cognitive functions dependent on the dorsolateral prefrontocortical region. Studies have reported some cognitive deficits in cocaine (Sevy et al., 1990, Serper et al., 2000) and alcohol (Allen et al., 1999, Bowie et al., 2005) abusers compared to non-substance users, but other studies did not find cognitive differences between substance abusers and non-substance users (Cleghorn et al., 1991, Nixon et al., 1996, Addington and Addington, 1997, Pencer and Addington, 2003). Discrepancies between studies in schizophrenia patients abusing alcohol may be age related, with cognitive deficits becoming more apparent in older patients abusing alcohol (Allen et al., 1999, Bowie et al., 2005).

Thus, we postulated that (1) schizophrenia patients have widespread cognitive deficits associated with the orbitofrontal prefrontal cortex (OFPFC) and dorsolateral prontal cortex (DLPFC) compared to healthy subjects; (2) deficits of the OFPFC are more specifically associated with a history of cannabis use disorders; and (3) deficits of the OFPFC are not associated with deficits of the DLPFC or other areas of the cortex. The latter hypothesis is also based on previous findings in individuals with substance use disorders showing no association between IGT deficits and cognitive deficits related to other areas of brain function (Grant et al., 2000).

To test the first hypothesis, we compared schizophrenia patients and healthy subjects on a battery of cognitive tests, which tap into DLPFC function, and with the IGT, which assays OFPFC function. We applied a computational model, the Expectancy-Valence model (Busemeyer and Stout, 2002, Yechiam et al., 2005) to identify the relative contributions of distinct components (attention to past outcomes, relative weight of wins and losses, choice strategies) to decisions made during performance of the IGT.

To examine the second hypothesis, we compared schizophrenia patients with and without cannabis use disorders on the same measures. We focused on cannabis because it is the most commonly used illicit drug in schizophrenia (Murray et al., 2003).

Finally, we tested the third hypothesis by examining correlations between performance on the IGT and performance on cognitive tests indexing parcellated aspects of the DLPFC.