Abnormal reward functioning across substance use disorders and major depressive disorder: Considering reward as a transdiagnostic mechanism
Introduction
Substance use disorders (SUD) and major depressive disorder (MDD) rank among the most widespread illnesses nationwide, with 12-month prevalence rates of 6.6% and 9.0%, respectively (Aldworth, 2009, Kessler and Wang, 2009). In the United States, they are also among the leading causes of disability (Mathers et al., 2008), with an estimated annual economic burden of $83.1 billion for MDD and $428.1 billion for SUD (Greenberg et al., 2003, Rice, 1999). Importantly, there exists significant psychiatric comorbidity between MDD and SUD, such that the presence of one disorder increases the risk of onset of the other. Among individuals with lifetime MDD, a history of comorbid SUD is common: 40.3% also have a history of an alcohol use disorder, 17.2% have a history of a drug use disorder, and 30.0% have a history of nicotine dependence (Hasin et al., 2005). Compared to individuals without any SUD, the odds of having current MDD are 2.5 times higher among individuals with a current SUD, 3.7 times higher with current alcohol dependence, and 9.0 times higher with current drug dependence (Grant et al., 2004). These epidemiological data indicate that MDD and SUD are closely related illnesses, with reciprocal impacts on the development of each disorder.
In addition to this well-documented comorbidity, both SUD and MDD are characterized by marked dysfunction in reward-seeking behavior (American Psychiatric Association, 2013). A cardinal symptom of MDD is anhedonia, a pervasive lack of interest or pleasure in activities that are normally enjoyable. A defining feature of SUD, meanwhile, is excessive pursuit and use of a substance that is disproportionate to the hedonic impact derived from it. For each disorder, there is considerable interest in integrating findings from the basic affective neuroscience literature on reward, with the ultimate goal of clarifying how dysfunction in neural circuits known to be involved in reward processing may give rise to these clinical phenomena (Forbes and Dahl, 2012, Pizzagalli et al., 2011, Volkow et al., 2009, Volkow et al., 2011). Not only is functioning in the reward circuity important for the etiopathogenesis of these disorders, but it has also been shown to change in response to treatment of these disorders, suggesting potentially novel targets for treatment (Heller et al., 2013, Kreek et al., 2002, Schlaepfer et al., 2008).
Despite this growing interest in utilizing a translational approach to understand reward processing abnormalities within SUD and MDD, the extant literatures are limited by the fact that these disorders have not been systematically contrasted with one another; that is, the nature of reward dysfunction across SUD and MDD remains largely unexplored. A broader research scope is warranted to substantiate the clinical utility of neurobiological indicators of reward dysfunction, one that: (a) contrasts SUD directly with MDD, and (b) considers the impact of comorbid SUD/MDD. Such an approach would address whether observed neurobiological abnormalities have diagnostic specificity, clarifying whether effects are unique to either MDD or SUD, or instead span both disorders, indicating possible transdiagnostic mechanisms of illness.
A second limitation of research that has been conducted to date is the tendency for individual studies to focus on a single outcome related to reward processing, rather than considering reward as a multi-faceted process. Human (e.g., neuroimaging, psychophysiological studies) and basic animal (e.g., conditioning and drug administration studies) neuroscience literatures indicate that reward is not a unitary construct, but instead is composed of three primary components with distinct neural circuitry: ‘liking’, which refers to the hedonic impact of reward consumption; ‘wanting’ or incentive salience, which refers to the motivation to pursue a reward; and learning, or the acquisition of reward–outcome contingencies (Berridge et al., 2009). Thus, rather than conceptualizing abnormal reward processing in SUD or MDD as a relatively global dysfunction (i.e., decreased vs. increased reactivity to rewards overall), the existing evidence indicates that a more nuanced pattern is likely (Treadway & Zald, 2011).
In order for progress to be made in linking abnormalities in reward processing to clinical phenomena in SUD and MDD, a multi-dimensional approach is required both in procedures for diagnosing these conditions and in the manner in which reward is assessed. Indeed, such an approach is highly consistent with the aims of the National Institute of Mental Health's Research Domain Criteria (RDoC) project (Cuthbert and Insel, 2013, Insel et al., 2010), an initiative which seeks to reclassify psychiatric illness based on quantifiable dysfunction in biologically-based constructs—irrespective of traditional diagnostic boundaries. A primary domain of functioning within RDoC is that of Positive Valence Systems, which delineates reward into constituent constructs of Initial/Sustained Responsiveness to Reward (i.e., ‘liking’), Approach Motivation (i.e., ‘wanting’), and Reward Learning/Habit. In addition to adopting a transdiagnostic perspective, a significant advantage of RDoC is the integration of multiple units of analysis, incorporating information from genetic, psychophysiological, behavioral, and self-report measures. RDoC provides a highly promising framework, yet there is little work to date aimed at developing a comprehensive understanding of reward function across multiple units of analysis and across multiple disorders.
Here, we seek to integrate the literatures on reward dysfunction in SUD and MDD with specific reference to the RDoC framework. While pertinent evidence remains incomplete, the goals of our review are to synthesize findings that currently exist, identify promising psychophysiological indicators of reward dysfunction using candidate analytic methods in relation to SUD/MDD, and outline how future studies may address critical gaps in our knowledge. We focus primarily on psychophysiological evidence (e.g., electroencephalography, or EEG; event-related potentials, or ERPs; functional magnetic resonance imaging, or fMRI), while also linking these with other units of analysis wherever possible (e.g., animal studies). First, we provide a brief overview of the basic neuroscience literature on reward. Next, we review the specific abnormalities in reward processing that have been identified to date within SUD and MDD. Finally, we suggest a framework for integrating these disparate literatures and discuss the utility of shifting investigative focus from individual clinical disorders to processes relevant to understanding broad liability and diagnostic co-morbidity. An integrative focus on abnormal reward functioning across the full clinical continuum, rather than solely within circumscribed diagnostic categories, may contribute to the refinement of clinical phenotypes such as SUD and MDD, and better predict the onset of and recovery from these disorders.
Section snippets
The neurobiology of reward
Recently, significant progress been made not only in parsing the psychological components of reward, but also in identifying the underlying neural mechanisms associated with each component. Overall, reward processes are represented in the brain by a complex network involving many cortical structures, including the orbitofrontal cortex (OFC) and anterior cingulate (ACC), as well as subcortical structures such as the nucleus accumbens (NAc), ventral tegmentum, ventral pallidum, amygdala, and
Reward dysfunction in substance use disorders
SUDs are defined by uncontrollable and compulsive seeking and use of drugs/alcohol, which persists in spite of negative health and social consequences. Different types of substances have different pharmacological and pharmacokinetic properties; however, their habit-forming effects involve a common denominator, namely, a dysfunction in reward circuitry. Increasingly, evidence demonstrates that substance abuse “hijacks” the neural circuitry of reward (Berridge & Robinson, 2003). More
Reward dysfunction in major depression
MDD is marked by persistent, debilitating low mood in conjunction with other characteristic cognitive and physical symptoms. Many of the commonly observed symptoms in MDD entail disturbances in functions regulated by reward circuitry, including disruptions in appetite, sleep, energy level, and pleasure, suggesting that reward dysfunction plays a fundamental role in the pathophysiology of MDD (Nestler et al., 2002, Nestler and Carlezon, 2006, Russo and Nestler, 2013). Of note, the primary
A multidimensional, transdiagnostic perspective on reward dysfunction
A substantial body of evidence indicates that both MDD and SUD are associated with dysfunctional reward processing across multiple units of analysis. These two literatures have grown in parallel with one another, but with a focus on one disorder or the other and limited consideration of their co-occurrence, despite the fact that SUD and MDD are commonly observed together and reciprocally impact the course of one another. To draw this research closer in line with the clinical reality of complex
Understanding the comorbidity between SUD and MDD
Rates of lifetime comorbidity between MDD and SUD are high (Kendler et al., 2003, Vaidyanathan et al., 2012, Watson, 2005). One possible explanation for these high rates may relate to dysfunction in reward circuitry. While dissociable deficits in reward ‘liking,’ ‘wanting,’ and learning are associated with SUD and MDD, changes within the reward system associated with one disorder may actually increase risk for alteration in additional reward-related processes. Though very little work has
Future directions & conclusions
Drawing from the already substantial basic science literature on reward, clarifying the nature of reward-related symptoms in SUD and MDD represents a great opportunity for translational neuroscience. In the short term, it is expected that a multidimensional approach to assessing reward dysfunction will help to account for variability within the existing diagnostic categories of MDD and SUD (i.e., differentiate individuals with the same diagnosis who have distinct profiles of reward
Authorship statement
Arielle Baskin-Sommers and Dan Foti contributed equally to this review. Both authors approved the final version of the paper for submission.
Acknowledgements
None.
References (210)
Frontal P300 decrement, childhood conduct disorder, family history, and predisposition of relapse among abstinent cocaine abusers
Drug Alcohol Depend.
(1997)CNS recovery from cocaine, cocaine and alcohol, or opioid dependence: a P300 study
Clin. Neurophysiol.
(2001)- et al.
P300 differences between nonalcoholic young men at average and above average risk for alcoholism: effects of distraction and task modality
Prog. Neuropsychopharmacol. Biol. Psychiatry
(1994) - et al.
Decision-making and addiction (part I): impaired activation of somatic states in substance dependent individuals when pondering decisions with negative future consequences
Neuropsychologia
(2002) - et al.
Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward?
Neuropsychologia
(2002) - et al.
Cocaine seeking habits depend upon dopamine dependent serial connectivity linking the ventral with the dorsal striatum
Neuron
(2008) - et al.
Violent offending predicts P300 amplitude
Int. J. Psychiatry
(2007) Food reward: brain substrates of “wanting” and “liking”
Neurosci. Biobehav. Rev.
(1996)- et al.
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Brain Res. Rev.
(1998) - et al.
Parsing reward
Trends Neurosci.
(2003)
Dissecting components of reward: ‘liking’, ‘wanting’, and learning
Curr. Opin. Pharmacol.
Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression
Biol. Psychiatry
Neural response to reward and depressive symptoms from late childhood to early adolescence
Biol. Psychol.
P300 amplitude in adolescent twins discordant and concordant for alcohol use disorders
Biol. Psychol.
Ventral striatal and medial prefrontal BOLD activation is correlated with reward-related electrocortical activity: a combined ERP and fMRI study
NeuroImage
Behavioral therapies for co-occurring substance use and mood disorders
Biol. Psychiatry
Can induced moods trigger drug-related responses in opiate patients
J. Subst. Abus. Treat.
Frontal P300 decrements, alcohol dependence, and antisocial personality disorder
Biol. Psychiatry
Distributed network actions by nicotine increase the threshold for spike-timing-dependent plasticity in prefrontal cortex
Neuron
Anterior cerebral asymmetry and the nature of emotion
Brain Cogn.
Neural mechanisms of risky decision-making and reward response in adolescent onset cannabis use disorder
Drug Alcohol Depend.
Nucleus accumbens shell and core dopamine: differential role in behavior and addiction
Behav. Brain Res.
Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes
J. Affect. Disord.
Cannabinoid receptor 1 (CNR1) gene: impact on antidepressant treatment response and emotion processing in Major Depression
Eur. Neuropsychopharmacol.
Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria
Biol. Psychiatry
Alcohol consumption impairs stimulus- and error-related processing during a Go/No-Go Task
Cogn. Brain Res.
Anger expression, coping, and substance use in adolescent offenders
Addict. Behav.
Depression and reduced sensitivity to non-rewards versus rewards: evidence from event-related potentials
Biol. Psychol.
Reward dysfunction in major depression: multimodal neuroimaging evidence for refining the melancholic phenotype
NeuroImage
Error-related negativity predicts reinforcement learning and conflict biases
Neuron
Error-processing deficits in patients with cocaine dependence
Biol. Psychol.
P3 event-related potential impairments in antisocial and psychopathic individuals: a meta-analysis
Biol. Psychol.
The effect of graded monetary reward on cognitive event-related potentials and behavior in young healthy adults
Int. J. Psychophysiol.
Neurometabolic effects of psilocybin, 4 methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers A double-blind, placebo-controlled PET study with [18F] FDG
Neuropsychopharmacology
The feedback-related negativity reflects the binary evaluation of good versus bad outcomes
Biol. Psychol.
Substance use disorders, externalizing psychopathology, and P300 event-related potential amplitude
Int. J. Psychophysiol.
Abnormal cerebral perfusion in chronic methamphetamine abusers: a study using 99MTc-HMPAO and SPECT
Prog. Neuropsychopharmacol. Biol. Psychiatry
Results from the 2007 National Survey on Drug Use and Health: National Findings
Quantitative EEG correlates of crack cocaine dependence
Psychiatry Res.
Diagnostic and Statistical Manual of Mental Disorders
The impact of cognitive control, incentives, and working memory load on the P3 responses of externalizing prisoners
Biol. Psychol.
Frontal P300 decrements in antisocial personality disorder
Alcohol. Clin. Exp. Res.
Individual differences in reward drive predict neural responses to images of food
J. Neurosci.
Risky business: emotion, decision-making, and addiction
J. Gambl. Stud.
Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions
Brain
A single-trial estimation of the feedback-related negativity and its relation to BOLD responses in a time-estimation task
J. Neurosci.
The debate over dopamine's role in reward: the case for incentive salience
Psychopharmacologia
Cooperative opioid and serotonergic mechanisms generate superior antidepressant-like effects in a mice model of depression
Int. J. Neuropsychopharmacol.
Active behaviours produced by antidepressants and opioids in the mouse tail suspension test
Int. J. Neuropsychopharmacol.
Self-report and behavioral measures of reward sensitivity predict the feedback negativity
Psychophysiology
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Both authors contributed equally to this work.