Differential impact of severity of drug use on frontal behavioral symptoms
Introduction
The human prefrontal cortex (PFC) plays a major role in the formulation and monitoring of goal directed actions, and it is also involved in high-order emotional regulation (Stuss & Knight, 2002). Regional specialization within the human PFC is as diverse as its functions, and three PFC-striato-thalamic circuits have been associated with different clinically observable behavioral syndromes: the anterior cingulate circuit (i.e., associated with apathy behavior), the orbitofrontal circuit (i.e., associated with disinhibition disorders), and the dorsolateral circuit (i.e., associated with executive dysfunction) (Cummings, 1993, Tekin and Cummings, 2002). A growing body of evidence from pre-clinical, neuropsychological, and brain imaging studies indicates that substance abuse is associated with damage to different functional circuits converging in the PFC (for review, see Garavan and Stout, 2005, Robinson and Kolb, 2004, Verdejo-García et al., 2004). However, the critical question that remains unanswered is whether these alterations preceded the substance abuse condition, or whether these abnormalities were the consequences of the abuse of these drugs.
One possible approach to addressing this question is to examine the extent to which dose-related or severity measures of substance abuse can predict the neurobehavioral alterations of substance abusers. A number of studies using this approach have demonstrated dose-related effects of drugs of abuse on a variety of cognitive domains related to the operations of the PFC. Cannabis dose-related measures have been moderately associated with poorer performance on tests of visual and verbal memory, psychomotor speed, executive function and decision-making (Bolla et al., 2002, Bolla et al., 2005, Verdejo-García et al., 2005). Cocaine use severity has been consistently associated with impaired performance on tests of inhibitory control and executive function (Bolla et al., 2000, Bolla et al., 1999, Fillmore and Rush, 2002, Roselli and Ardila, 1996, Verdejo-García et al., 2005). Recent studies have also supported dose-related effects of opiate and amphetamine use on executive control measures (Lyvers and Yakimoff, 2003, Rogers et al., 1999). In the case of MDMA (ecstasy), although several studies have shown dose-related detrimental effects of ecstasy on memory and executive functioning (Bolla et al., 1998, Fox et al., 2001, Verdejo-García et al., 2005), one must use caution in interpreting the effects of ecstasy on cognition, since the drug is almost always co-abused with marijuana or cocaine, thus rendering it difficult to determine whether the deficits are linked to ecstasy or other drug use (Croft et al., 2001, Dafters et al., 2004, Gonzalez et al., 2004). In contrast, severity of alcohol abuse has been consistently associated with impaired performance on tests of executive functioning and with damage to different regions of the PFC (Adams et al., 1995).
Although extensive evidence supports the relationship between drug use severity and poorer performance on cognitive tests sensitive to PFC alterations, few studies have examined the effects of drug use-related measures on behavioral problems associated with the functioning of different PFC circuits. To our knowledge, only one previous study (Spinella, 2003) analysed the relationship between severity of drug use and PFC-associated behavior in a non-clinical sample of community adults, in which drug use was present to some degree. The results of this study showed that tobacco use severity was positively correlated with higher scores on the three subscales of the Frontal Systems Behavior Scale (FrSBe): apathy, disinhibition, and executive dysfunction. However, no significant correlations were found between frequency of use of cannabis, stimulants, opioids or ecstasy and FrSBe scores. Subsequent group analyses in this sample showed that poly-substance users presented higher disinhibition scores than non-users.
The aim of this study is to examine the extent to which severity of use of several drugs (including alcohol, cannabis, cocaine, heroin, and MDMA) correctly predicts PFC related behavioral problems in a clinical sample of poly-substance abusers. We will examine the relationship between severity of drug use and neurobehavioral deficits attributed to abnormal functioning of PFC systems: apathy, disinhibition, and executive dysfunction. According to previous results indicating a significant relationship between severity of drug use and cognitive-executive deficits in clinical samples of substance abusers, we hypothesize that drug use severity will be associated with greater frontal behavioral problems across different domains.
Section snippets
Participants
Thirty-two abstinent poly-substance abusers (26 males) were recruited as they joined an addiction rehabilitation program. All of them had gone through a withdrawal period from the diverse drugs. None of them was following methadone maintenance treatment or any other pharmacological substitution treatment during the course of the neuropsychological testing. Potential participants who had previously been diagnosed with any other disorder or showed signs of any disorder from DSM-IV Axes 1 and 2
Results
A descriptive summary of participants' scores on the three FrSBe subscales (apathy, disinhibition and executive dysfunction) and FrSBe total score, and descriptive normative values for the FrSBe are presented in Table 2. As shown in Table 2, substance abusers (both males and females) in this sample showed a mild increase (approximately 0.5 standard deviations above the mean) in their scores on the FrSBe subscales and FrSBe total score with regard to published normative values (Grace & Malloy,
Discussion
In poly-substance abusers, there is a consistent relationship between severity of drug use and several PFC associated behavioral symptoms, including apathy, disinhibition, and executive dysfunction. This relationship was not uniform across the various substances abused in this sample. Higher severity of alcohol, cannabis and heroin use was associated with higher apathy scores. Severity of use of cannabis, cocaine and ecstasy correctly predicted higher disinhibition scores. Finally, higher
Acknowledgements
This study was supported with funds from Project BSO2003-07169 from the Spanish Ministerio de Ciencia y Tecnología (MCYT) and INT/2012/2002 from the Spanish Ministerio del Interior.
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