Pathological Gamblers Demonstrate Frontal Lobe Impairment Consistent With That of Methamphetamine-Dependent Individuals

Participants included nine nontreatment-seeking pathological gamblers, 29 nontreatment-seeking methamphetamine-dependent individuals, and 19 comparison subjects. Demographics, substance use, and gambling profiles are detailed in Table 1 . All subjects were recruited from the community through advertisements in local newspapers and flyers at local casinos. Potential participants were excluded for a history of stroke, traumatic brain injury (loss of consciousness greater than 20 minutes), epilepsy, or attention deficit disorder or for testing HIV seropositive. We used the Structured Clinical Interview for DSM-IV 10 to rule out the presence of axis I or axis II disorders. We collected urine toxicology screens from each participant to verify either the presence of methamphetamine for the methamphetamine group or the absence of illicit drugs in the comparison and pathological gambling group. Participants gave written informed consent after being apprised of the study risks and were reimbursed for participation.

The pathological gamblers met DSM-IV criteria for pathological gambling. They were required to have gambled within 2 weeks of the assessment and could not be actively involved in any formalized treatment other than Gambler’s Anonymous. Moreover, they were excluded if they met DSM-IV criteria for abuse of or dependence on any drug and/or if they had a positive urine toxicology screen.

The methamphetamine-dependent sample met DSM-IV criteria for methamphetamine dependence based on the SCID. Subjects may have used other illicit substances but did not meet DSM-IV criteria for dependence on them at the time or previously. They reported using at least 0.5 g of methamphetamine per week for the 6 months prior to the study. The route of methamphetamine administration for each of the drug users was inhalation (snorting) and smoking.

Comparison subjects did not meet DSM-IV criteria for pathological gambling. They also did not meet DSM-IV criteria for abuse of or dependence on any drug at the time or in the past and had a negative urine toxicology screen.

Once enrolled in the study, methamphetamine users were asked to discontinue use of methamphetamine. Participants were included in the study only if 1) on the date of the screening examination that was conducted within 2 weeks of the assessment, their urine tested positive for methamphetamine and tested negative for other drugs, such as cocaine, marijuana, opiates, PCP, and alcohol; 2) they produced a urine sample that was negative for methamphetamine and other drugs on the day in which the neurocognitive measures were administered; and 3) they were not experiencing clinically significant levels of withdrawal, such as insomnia, reduced appetite, or a mood disorder. The negative urine test indicated that all subjects had ceased using methamphetamine at least 5 days prior to the neurocognitive assessment, based on the elimination half-life of methamphetamine of approximately 12 hours. 19 This was considered to be a sufficient length of time for the “crash” phase, consisting of symptoms such as dysphoria, slowing, and agitation, to resolve.

Table 1 shows that pathological gamblers, methamphetamine-dependent volunteers, and healthy comparison subjects did not differ in terms of gender, education, estimated premorbid intellectual functioning, or severity of self-reported depressive symptomatology. Although the groups differed with respect to age, covariate analyses revealed that age did not correlate with performance on the neurocognitive measures; thus, multivariate ANOVA was utilized to measure group differences in test performance. The multivariate ANOVA revealed that the gamblers, methamphetamine dependent volunteers, and nondrug-using comparison subjects differed significantly with respect to their performance on the frontal lobe measures (F=3.95, df=6,98; p≤0.01). Eta squared, which estimated the magnitude of the group differences, was 0.20, which is considered to be large.

Table 2 shows that the groups differed significantly on each of the three frontal lobe measures. The pathological gamblers performed significantly less well than the comparison subjects on each of the three measures (p<0.05). The performance of the pathological gamblers was similar to that of the methamphetamine users on the Ruff Figural Fluency Test and the Stroop Color Word Test but significantly worse than the methamphetamine users on Trail-Making Test, Part B (p<0.01). Eta squared, which estimated the magnitude of the group differences, ranged from 0.16 to 0.27, which is considered to be moderate to large.

These findings are the first, to our knowledge, to demonstrate that pathological gambling is associated with impairments across a range of timed measures that are frequently used by neuropsychologists for the purpose of documenting frontal lobe dysfunction. This finding implicates abnormalities in frontal-subcortical pathways, which mediate performance on these measures. 25 Future studies, such as those using simple and complex measures of reaction time, will assist in determining whether poor performance on these measures is the result of slowed information processing and/or a frontal lobe defect, per se. For example, slowed information processing may interfere with the ability of pathological gamblers to process all of the information presented to them; as a result, they will be at risk to make decisions without considering information that potentially is salient to those decisions.

Based on the findings from related studies, we can speculate regarding the specific mechanism(s) of the frontal impairments in pathological gambling. For example, neuroimaging studies have shown that pathological gamblers demonstrated decreased blood oxygenation levels in left ventromedial cortex using fMRI. 7 Moreover, Reuter et al. 26 replicated and expanded upon this finding by showing that hypoactivation of ventral striatal and ventromedial prefrontal regions was associated with disease severity.

Though these findings preliminarily show that pathological gambling is associated with frontal impairment, several limitations should be noted with respect to the current study. For example, the pathological gamblers were older than the volunteers in other groups. Although this issue was addressed using covariate analysis and by determining that age was not associated with test performance in this sample, it would be helpful to include an age-matched sample in future studies. Additionally, the sample size was not large enough to identify risk or protective factors distinguishing between impaired and nonimpaired gamblers. Likely risk factors for frontal lobe impairment that should be considered in future studies might include frequency or duration of pathological gambling, or demographic factors, such as age, education, and socioeconomic status, and other comorbid disorders, such as attention deficit hyperactivity disorder, which affects a disproportionate number of pathological gamblers relative to the general population. 27 – 29 In addition, it may be useful to conduct collateral interviews and/or obtain collateral data sources (e.g., previous treatment records) in order to verify the self-reports of study participants. Moreover, the sample size limits the degree to which these findings may be generalized to gamblers with different demographic profiles, such as younger or older pathological gamblers with higher levels of education. Furthermore, serial assessments in abstinent individuals with pathological gambling will clarify the durability of these findings.

At present, the etiology of the frontal lobe deficits remains unclear. Because the study design was cross-sectional, it was not feasible to address this issue in a conclusive manner; however, by recruiting gamblers with limited comorbid psychopathology, these findings tentatively suggest that pathological gambling is a risk factor per se for frontal lobe dysfunction. Serial assessments of gamblers without comorbid disorders who are not abstinent or who are abstinent for various lengths of time will assist in providing additional insight into the manner in which pathological gambling affects frontal lobe function. Moreover, serial assessments might also clarify the particular association between potential changes in frontal lobe function and changes in gambling strategies. For example, if serial assessments reveal deterioration in frontal lobe functioning, it will be interesting to determine whether the gamblers are more likely to utilize poor strategies and/or behave more impulsively.

Findings from this study carry several implications for future work. First, future studies need to address how these neurocognitive impairments relate to pathological gambling behaviors. It is possible that these deficits are responsible for persistent gambling through a failure to inhibit behaviors or perhaps through an inability to adapt to continual losing. In addition, future studies need to determine how these measures of frontal lobe functioning can assist clinicians with regard to providing focused care for their patients. Additionally, if the impairments persist following the cessation of pathological gambling, then future studies might consider the use of reconceptualizing psychotherapeutic interventions as a means of circumventing them 30 – 32 as well as identifying medications that can ameliorate them.

This study was supported by grants from the National Institute on Drug Abuse (K24 DA17754, R25DA014593, R03DA020591) and a gift from the Annenberg Foundation.

Received April 26, 2006; revised September 28, 2006; accepted October 2, 2006. Drs. Kalechstein, Fong, Rosenthal, Davis, Vanto, and Newton are affiliated with the Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California. Address correspondence to Dr. Kalechstein, David Geffen School of Medicine at UCLA, 760 Westwood Boulevard, Room C8-887, Los Angeles, CA 90024; [email protected] (e-mail).