Comparison of impulsivity and working memory in cocaine addiction and pathological gambling: Implications for cocaine-induced neurotoxicity

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Abstract

Background

The aim of this study was to compare the cognitive performance of cocaine dependent individuals (CDI) with that of pathological gamblers (PG). Cocaine dependence and pathological gambling share neurobiological vulnerabilities related to addiction, but PG are relatively free of the toxic consequences, such that any additional deficits observed in CDI may be interpreted as pertaining to specific drug effects.

Methods

We used a case–control observational design contrasting multiple measures of impulsivity (UPPS-P trait impulsivity, delay discounting) and executive measures of response inhibition (Stroop) and working memory performance (N-back) between groups of CDI (n = 29), PG (n = 23), and healthy controls (n = 20). We conducted one-way ANOVAs, followed by planned pairwise tests and calculations of Cohen's d to estimate significant differences between the groups.

Results

CDI, as compared to PG, had elevated scores on UPPS-P Negative Urgency and poorer performance on working memory (2-back). PG had steeper delay-discounting rates. Both groups had elevated Positive Urgency and poorer Stroop inhibition compared to controls. Peak amount of cocaine use was negatively correlated with working memory and response inhibition performance.

Conclusion

We found cocaine-related specific elevations in Negative Urgency and working memory deficits, putatively identified as cocaine neurotoxicity effects. Other aspects of impulsivity (Positive Urgency, Stroop inhibition) were increased across CDI and PG groups and may reflect vulnerability factors for addiction.

Introduction

Cocaine use is, after cannabis, the second most widely used illegal drug in Europe and the US, with one of the highest rates of substance dependence and treatment demand in the past year (EMCDDA, 2011, Substance Abuse and Mental Health Services Administration, 2011). Cocaine addiction is characterized by rapid and intense hedonic effects and binging patterns of administration, followed by strong cravings, stress and negative affect during abstinence (Goldstein and Volkow, 2002). Chronic cocaine use is also associated with robust cognitive deficits, especially in the domains of working memory, response inhibition, and impulsive decision-making (see review in Fernández-Serrano et al., 2011a). These cognitive-executive deficits have relevance for the etiology and treatment of cocaine use disorders: they may confer risk for drug use initiation, and facilitate transitions between recreational use and substance dependence (George and Koob, 2010, Verdejo-García et al., 2008); and they may also hinder cocaine use behavior change by buffering the beneficial effects of treatment interventions, or favoring poor compliance and relapse (Aharonovich et al., 2008, Streeter et al., 2008, Turner et al., 2009). To further understand these processes, it is important to dissociate the specific harmful effects of cocaine use on cognition, from the cognitive traits that predispose the initiation and escalation of drug-taking (Kreek et al., 2005).

The purpose of this study was to compare the cognitive performance of cocaine dependent individuals (CDI) with that of pathological gamblers (PG). Pathological gambling is increasingly viewed as a behavioral addiction, which shares core features with other substance addictions, including vulnerability mechanisms (e.g., genetics, impulsive personality), clinical features (e.g., craving, frequent relapses), and neurobiological alterations in frontostriatal systems (Bowden-Jones and Clark, 2011, Potenza, 2009). The direct comparison of CDI and PG may be informative for at least two reasons. First, these two disorders have some notable similarities in terms of subjective effects, reinforcing schedules, and temporal patterns of consumption (characterized by intense episodes of repeated administration [“binges”] followed by periods of abstinence). In fact, the possibility to play a game of chance is an effective competitive option to decrease cocaine self-administration in humans (Vosburg et al., 2010). In these respects, cocaine addiction is arguably more similar to pathological gambling than other forms of drug dependence. Second, this comparison may increase our understanding about the extent of cognitive impairment occurring as a consequence of cocaine use. Cocaine dependence and pathological gambling share the neurobiological vulnerability that may confer higher risk for addictions, but one assumes that PG (without drug comorbidities) are spared from the toxic consequences, such that the additional deficits observed in cocaine addiction may be interpreted as pertaining to specific drug effects.

The neuropsychological literature in cocaine dependence highlight deficits related to impulsivity and executive functions. However, important differences emerge as a function of severity of cocaine dependence. For example, recreational cocaine users have deficits in inhibitory control, but not in working memory or set-shifting (Colzato et al., 2007, Colzato et al., 2009). They also show relatively higher elevations of certain impulsivity dimensions, including Lack of Perseverance (akin to Barratt's attentional impulsivity) and Positive Urgency (the tendency to commit impulsive acts when under strong positive affect; Verdejo-García et al., 2010). Conversely, cocaine dependence is associated with robust impairments in working memory, delay-discounting and reinforcement-learning/perseveration (Fernández-Serrano et al., 2011b, Woicik et al., 2011). These findings are in agreement with animal studies, which demonstrate that chronic administration of cocaine induces deficits in working memory and cognitive flexibility, likely via neurotoxic effects on prefrontal cortex, hippocampus and basolateral amygdala (Porter et al., 2011, Stalnaker et al., 2007, Sudai et al., 2010). CDI also show prominent deficits in emotion regulation, which are associated with higher stress reactivity and diminished impulse control (Fox et al., 2011). Indeed, Negative Urgency – the tendency to commit impulsive acts when under intense negative affect, is the main predictor of the severity of addiction-related problems in stimulant-dependent individuals (Verdejo-García et al., 2007).

Previous neuropsychological studies in PG have also demonstrated robust deficits on several aspects of impulsivity – response inhibition, delay discounting and impulsive decision-making (Fuentes et al., 2006, Goudriaan et al., 2006, Kertzman et al., 2008, Lawrence et al., 2009a, Lawrence et al., 2009b, Michalczuk et al., 2011). As for trait impulsivity, the dimension of Positive Urgency is specifically associated with escalation of gambling behavior in community youths (Cyders and Smith, 2008), whereas PG show clinically significant increases both in Positive and in Negative Urgency (Michalczuk et al., 2011). Conversely, the degree of executive dysfunction in PG is far from clear – studies reporting positive findings have been frequently conducted in small, unrepresentative samples (see review in van Holst et al., 2010), and at least three studies have demonstrated a dissociation between cognitive impulsivity deficits, in the context of intact working memory or cognitive flexibility (Cavedini et al., 2002, Goudriaan et al., 2006, Lawrence et al., 2009a, Lawrence et al., 2009b).

With these issues in mind, we compared the neuropsychological performance of CDI, PG, and healthy controls (HC) on probes of working memory and response inhibition/flexibility. We also employed the UPPS-P scale of impulsive behavior to quantify the five dimensions pertaining to trait impulsivity, and the delay discounting questionnaire to assess relative preference for immediate vs. delayed rewards. We hypothesized that CDI and PG would have similar cognitive deficits in domains associated with addiction liability, namely delay discounting and response inhibition. On the other hand, we predicted that CDI would have poorer performance than PG in domains associated with cocaine-induced neurotoxicity – working memory and flexibility. With regard to trait impulsivity, in accordance with previous evidence, we hypothesized that CDI and PG would share significant elevations in positive and Negative Urgency, with more robust effects of Negative Urgency on cocaine patients, due to the impact of the drug on emotion regulation systems.

Section snippets

Participants

Twenty-nine CDI, 23 PG, and 20 non-drug using, non-gambling healthy controls (HC) participated in this study. CDI were recruited as they commenced treatment in the clinic “Centro Provincial de Drogodependencias (CPD)” in Granada (Spain). This public facility provides CBT-based treatment for substance use related disorders in an outpatient basis. PG were recruited as they commenced treatment in the outpatient center “Asociación Granadina de Jugadores en Rehabilitación (AGRAJER)” in Granada

Differences between CDI, PG and HC on Impulsivity measures

UPPS: We found significant differences between the groups in the dimensions of Positive Urgency, F(2,64) = 10.92, p < 0.001, and Negative Urgency, F(2,64) = 19.48, p < 0.001. Pairwise tests showed that in the case of Positive Urgency both CDI and PG scored higher than HC (p < 0.001, and p = 0.004, respectively), but the CDI and PG groups did not differ significantly (p = 0.108). In the case of Negative Urgency, CDI scored significantly higher than both PG (p = 0.01) and HC (p < 0.001); PG also scored higher than

Discussion

We found that CDI, as compared to PG, had elevated scores on Negative Urgency and poorer performance on working memory (2-back). Conversely, compared to the cocaine group, pathological gamblers had steeper delay-discounting rates. Both cocaine dependent individuals and pathological gamblers, when compared to healthy controls, had elevated Positive Urgency and poorer response inhibition. Correlation analyses showed significant negative associations between the peak amount of cocaine use and

Role of funding source

Nothing declared.

Contributors

A. Verdejo-García, J.M. González-Martínez, Óscar Lozano and L. Clark designed the study. N. Albein-Urios performed clinical and neuropsychological assessments and wrote-up a first draft of the Manuscript. All authors contributed to the final version of the manuscript.

Conflict of interest

No conflict declared.

Acknowledgment

This study was funded by the Grant COPERNICO from the Plan Nacional sobre Drogas – Ministerio de Sanidad y Consumo (Convocatoria 2009).

References (63)

  • A. Verdejo-García et al.

    Impulsivity as a vulnerability maker for substance use disorders: review of findings from high-risk research, problem gamblers and genetic association studies

    Neurosci. Biobehav. Rev.

    (2008)
  • S.K. Vosburg et al.

    Using a novel alternative to drug choice in a human laboratory model of a cocaine binge: a game of chance

    Drug Alcohol Depend.

    (2010)
  • S.P. Whiteside et al.

    The five factor model and impulsivity: using a structural model of personality to understand impulsivity

    Pers. Individ. Dif.

    (2001)
  • P.A. Woicik et al.

    A pattern of perseveration in cocaine addiction may reveal neurocognitive processes implicit in the Wisconsin Card Sorting Test

    Neuropsychologia

    (2011)
  • E. Aharonovich et al.

    Cognition, commitment language, and behavioral change among cocaine-dependent patients

    Psychol. Addict. Behav.

    (2008)
  • A. Bechara

    Risky business: emotion, decision-making, and addiction

    J. Gambl. Stud.

    (2003)
  • K. Bolla et al.

    Prefrontal cortical dysfunction in abstinent cocaine abusers

    J. Neuropsychiatry Clin. Neurosci.

    (2004)
  • H. Bowden-Jones et al.

    Pathological gambling: a neurobiological and clinical update

    Br. J. Psychiatry

    (2011)
  • J.J. Canales

    Comparative neuroscience of stimulant-induced memory dysfunction: role for neurogenesis in the adult hippocampus

    Behav. Pharmacol.

    (2010)
  • R.N. Cardinal et al.

    ANOVA for the Behavioural Sciences Researcher

    (2006)
  • S. Carlson et al.

    Distribution of cortical activation during visuospatial n-back tasks as revealed by functional magnetic resonance imaging

    Cereb. Cortex

    (1998)
  • L.S. Colzato et al.

    Recreational cocaine polydrug use impairs cognitive flexibility but not working memory

    Psychopharmacology

    (2009)
  • L.S. Colzato et al.

    Impaired inhibitory control in recreational cocaine users

    PLoS One

    (2007)
  • M.A. Cyders et al.

    Emotion-based dispositions to rash action: positive and negative urgency

    Psychol. Bull.

    (2008)
  • D.C. Delis et al.

    Delis-Kaplan Executive Function System (D-KEFS)

    (2001)
  • Diagnostic and Statistical Manual of Mental Disorders-Revised (DSM-IV), 1994. American Psychiatric Association,...
  • European Monitoring Centre on Drugs and Drug Addiction, 2011. Statistical Bulletin, 2011. Retrieved from:...
  • M.J. Fernández-Serrano et al.

    Neuropsychological profiling of impulsivity and compulsivity in cocaine dependent individuals

    Psychopharmacology

    (2011)
  • M. Field et al.

    The smoking Stroop and delay discounting in smokers: effects of environmental smoking cues

    J. Psychopharmacol.

    (2006)
  • M. Field et al.

    Delay discounting and the behavioural economics of cigarette purchases in smokers: the effects of nicotine deprivation

    Psychopharmacology

    (2006)
  • M.B. First et al.

    Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I)

    (1997)
  • Cited by (0)

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