Whereas acts with impulsive or compulsive features may contribute specifically to creativity and endurance and generally to adaptive human behavior, disordered regulation of impulsive or compulsive behavior may be associated with adverse consequences and have a function in the development of mental disorder. Impulsivity may be defined as ‘a predisposition toward rapid, unplanned reactions to internal or external stimuli with diminished regard to the negative consequences of these reactions to the impulsive individual or to others' (Chamberlain and Sahakian, 2007
; Potenza, 2007b
). In contrast, compulsivity represents a tendency to perform unpleasantly repetitive acts in a habitual or stereotyped manner to prevent perceived negative consequences, leading to functional impairment (WHO, 1992
; Hollander and Cohen, 1996
; Chamberlain et al, 2006b
). These two constructs may be viewed as diametrically opposed, or alternatively, as similar, in that each implies a dysfunction of impulse control (Stein and Hollander, 1995
). Each potentially involves alteration within a wide range of neural processes, including attention, perception, and coordination of motor or cognitive responses.
Neuroanatomical models posit the existence of separate but intercommunicating ‘compulsive' and ‘impulsive' cortico-striatal circuits, differentially modulated by neurotransmitters (Robbins, 2007
; Brewer and Potenza, 2008
). In the compulsive circuit, a striatal component (caudate nucleus) may drive compulsive behaviors and a prefrontal component (orbitofrontal cortex, OFC) may exert inhibitory control over them. Similarly, in the impulsive circuit, a striatal component (ventral striatum/nucleus accumbens shell) may drive impulsive behaviors and a prefrontal component (anterior cingulate/ventromedial prefrontal cortex, VMPFC) may exert inhibitory control. Thus, in this model, there exist at least two striatal neural circuitries (one compulsive and one impulsive) that drive these behaviors, and two corresponding prefrontal circuitries that restrain these behaviors. Hyperactivity within the striatal components or abnormalities (presumably hypoactivity) in the prefrontal components may thus result in an increased automatic tendency for executing impulsive or compulsive behaviors, depending on the sub-component afflicted. Other possible abnormalities within cortico-striatal circuits (eg related to diminished striatal activation to rewards) may also contribute to seemingly impulsive or compulsive behaviors during engagement in reward-related behaviors. These pathologies can be explored using tasks of cognitive performance that tap into these specific functions and/or by functional imaging studies that measure activity within these neural systems. Overlap between these functional systems, so that what starts out as a problem in the impulsive circuit may end up as a problem in the compulsive circuit and vice versa, may contribute toward the impulsive–compulsive diathesis model proposed by Hollander and Wong (1995)
(Brewer and Potenza, 2008
There exist certain mental disorders for which impulsive and compulsive behaviors seem, at least on phenotypic grounds, to be the core and most damaging ingredient. These often highly heritable disorders, currently classified across several DSM-IV-TR (APA) diagnostic categories, include obsessive–compulsive disorder (OCD), body dysmorphic disorder, Tourette's syndrome, trichotillomania, attention deficit hyperactivity disorder (ADHD), pathological gambling, and substance addictions (SAs). Of interest, autism is characterized by both compulsive behavior (as one of the three core symptom domains) as well as impulsive behavior (as one of the associated symptom domains).
Traditionally, compulsive and impulsive disorders have been viewed at opposite ends of a single dimension; the former driven by a desire to avoid harm and the latter by reward-seeking behavior. However, convergent evidence from translational studies suggests that a shared tendency toward behavioral disinhibition, presumably resulting from failures in ‘top–down' cortical control of fronto-striatal circuits, or alternatively from overactivity within striatal circuitry, may crucially underpin both impulsive and compulsive disorders. Thus, rather than polar opposites, compulsivity and impulsivity may represent key orthogonal factors that each contribute to varying degrees across these disorders.
Many of these disorders tend to occur together, either within the same individual or clustering within families, implying the possibility of shared pathophysiological mechanisms (Hollander et al, 2007b
). Moreover, there is evidence of overlap in the treatment-response across some disorders. OCD typically responds to serotonin reuptake inhibitors (SRIs; clomipramine and selective SRIs, SSRIs) and to SSRIs combined with antipsychotic agents (Fineberg et al, 2005
). Antipsychotics represent first-line treatment for Tourette's syndrome, and it is, therefore, interesting that their combination with SSRIs shows greater efficacy in tic-related OCD (Bloch et al, 2006
). Compulsions associated with autistic disorders may also respond to low-dose SSRI and to antipsychotics (Kolevzon et al, 2006
). Trichotillomania may respond to SRIs and to antipsychotics, though confirmation in controlled studies is required (Chamberlain et al, 2007d
). ADHD, on the other hand, responds to noradrenergic reuptake inhibitors as well as dopaminergic agents (eg amphetamine), pathological gambling, and substance abuse disorders may also share a therapeutic response to opiate antagonists (Brewer et al, 2008
Attribution of cause and effect, using clinical data alone, may be confounded by the multiplicity of associated symptom domains that occur within complex mental disorders. Indeed, this group of disorders is characterized by considerable phenotypic heterogeneity and overlap. For example, some cases with autism show no symptoms of ADHD or compulsive behavior, others show ADHD, others OCD, and yet others show repetitive motor behaviors that do not resemble OCD. Translational research investigates from the perspective of underlying mechanisms, and may thus be capable of pinpointing neural contributions driving specific aspects of mental disorder. Endophenotypes are measurable, heritable traits, theoretically situated in an intermediate position between the clinical phenotype and the disease-susceptibility genotype. Such ‘intermediate phenotypes' are hypothesized to be more directly related to genetic risk for polygenic mental disorders than clinically expressed behaviors (Gottesman and Gould, 2003
; Chamberlain and Menzies, 2009
). Endophenotypic models of disease may be helpful for clarifying our understanding of the genetic basis of complex brain disorders and thus for informing diagnostic classification. Currently, impulsive and compulsive disorders are classified within disparate DSM-IV categories. As the American Psychiatric Association considers the re-classification of OCD, anxiety disorders and impulse-control disorders (ICDs) for the forthcoming DSM-V revision (Fineberg et al, 2007a
), it is timely to review the underpinning mechanisms of these disorders.
In this narrative review, we consider the neural and neuropsychological mechanisms associated with impulsive and compulsive acts and their contribution toward examples of impulsive and compulsive disorders. We assemble relevant findings from a broad range of complementary data, comprising recently published and as yet unpublished translational studies, human endophenotypic research, and clinical treatment trials, including ongoing work from our own units in the United Kingdom and the United States. Our analysis focusses on probing the parallel, functionally segregated, cortico-striatal neural projections from OFC to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/VMPFC to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the cross-talk between them (Robbins, 2007
; Brewer and Potenza, 2008
Figure 1 Compulsivity and impulsivity: candidate neural processes contributing to mental disorders. Although impulsive and compulsive disorders can be thought of as polar opposites, failures in cortical control of fronto-striatal neural circuits may underpin both (more ...)
Using these data, we attempt to address key questions including: (i) how much do compulsivity and impulsivity contribute to these disorders, (ii) to what extent do they depend on shared or separate neural circuitry, (iii) what are the mediating monoaminergic mechanisms, (iv) do impulsive or compulsive behavioral components have any prognostic value related to clinical treatment, and (v) is there a unifying-dimensional model that fully accommodates these data? We also draw attention to prospects for future research we believe may most fruitfully advance the field.