Impulsivity has been recognized as a multi-dimensional construct associated with an array of psychiatric disorders . It results in a tendency to engage in inappropriate, maladaptive or poorly conceived behaviors characterized by absence of forethought or consideration of outcomes, delayed gratification, novelty-seeking, impatience, short attention span, difficulty to persiste at a particular activity .
Behavioral, neurobiological, and imaging techniques have evidenced the association of impulsive behaviors with alcohol and drug abuse, both as a vulnerability markers and as a consequences [2, 3]. In fact, substance users are known to be highly impulsive and present a variety of well identified symptoms: impaired control, social impairment, risky use, and pharmacological tolerance and withdrawal . On the other hand, impulsivity may be understood as an imbalance of bottom-up and top-down neural systems suppressed by automatic or reward-driven responses with diminished cognitive control to demands .
Clinical evidence shows that impulsivity and substance use disorders (SUD) can coexist and can be related to the same environmental factors . This complex relationship shall be analyzed considering three main factors: i) impulsivity as a trait with focus on decreased cognitive and response inhibition; ii) the effect of acute or chronic substance use on brain structure and function; and iii) genetic and environmental factors [3, 4].
From a neurobiological perspective, both impulsivity and drug abuse have been associated with changes in dopaminergic processes . It has been evidenced that, in individuals with SUD, increased brain dopamine concentrations, in limbic brain regions, are responsible for reinforcing effects . However, the mechanisms involved in drug dependence are far more complex and rely also on structural changes of the prefrontal cortex (PFC) with reduction of the activity of this region, through a mechanism of downregulation of dopamine receptors type 2 (DRD2), in the striatum, resulting in impaired self-control and impulsive behaviours . On the other hand, research indicates that impulsivity is also modulated by the levels of dopamine in the PFC .
Dopamine metabolism in the PFC and limbic brain depends mostly on catechol-O-methyltransferase (COMT) . In fact, COMT is the primary mechanism for dopaminergic inactivation in the PFC  and is widely distributed in human brain. Still, research evidenced that, COMT is directly involved in the regulation of synaptic dopamine concentration in prefrontal neurons . In the striatum, this mechanism is regulated through neuronal uptake of dopamine by abundant specific transporters. In this context, low COMT activity would result in increased concentration of dopamine at the synapse and, therefore, in higher action at the dopamine receptors of the receiving neuron. However, several studies evidenced an inverted-U-shaped relationship between extracellular dopamine concentration and global PFC network activity [10, 11], so that both excessive and insufficient levels may impair cognitive performance. This could suggest the existence of a COMT mediated mechanism through which optimal levels of dopamine can modulate signal gain to support cognitive functioning.
Soluble COMT (s-COMT) activity has been assessed in the setting of impulsivity and SUDs with the objective of clarifying the physiological mechanisms underlying these disorders [3, 12]. We postulate that, considering all the aspects of dopamine brain metabolism, it is possible that individuals with excessively high but also those with low COMT activity could display high impulsivity and, perhaps, more severe dependence due to impaired self-control.
Despite all this and considering that addictive behaviors may also have a genetic component, the presence of one or more variant genes might act as risk factor for drug addiction. Since dopamine is the main neurotransmitter involved in the reward pathway, genes related with dopamine synthesis, degradation, receptors, and transporters are possible research topics . In this context, the COMT Val158Met (rs4680) polymorphism has been studied in the scope of drug addiction with evidence of a significant correlation in drug addicted patients [14, 15]. The COMT Val158Met polymorphism determines the dopamine concentration in the prefrontal cortex (PFC), but not in the striatum . In fact, we can find only a few DRD2 receptors in the PFC . However, they are abundant in the striatum, meaning that, to evaluate the dopaminergic component of addiction, dopamine receptors shall also be investigated. In this setting, several studies have shown that Taq I A1 allele of the DRD2 gene is associated with alcoholism, drug abuse, and other impulsive behaviors and personality traits so that it became a topic of research during the characterization of individuals with SUD [13, 18].
In incarcerated populations, drug abuse and psychiatric and psychological disorders, like impulsivity, are expressive and, as such, prisons are an adequate environment to collect data that can clarify the neurobiology of this association and improve the search for novel therapeutic approaches . Even though the dopaminergic pathways of SUD have already been studied, as far as we know, this kind of evaluation has never been performed in combination with impulsivity assessment in incarcerated individuals.
In this study, we intended to evaluate the dopaminergic function in imprisoned SUD offenders through of the correlation between s-COMT activity, impulsivity and dependence severity.