- Publisher Description
- The genetics of addiction—a translational perspective | Translational Psychiatry
- Scope and Format
- Substance dependence
Dysregulated and negative mood play a key role in the development of addictive disorders. Negative reinforcement models of substance use posit that the use of drugs serves to regulate emotion by removing the stimulus responsible for the experience of negative affect and symptoms of withdrawal with increasingly severe SUDs , thus further reinforcing subsequent use of drugs over time [ 73 , 74 , 75 ].
The dual systems model highlights how emotion regulation difficulties, reward-seeking, sensation-seeking, and impulsivity increase during adolescence, placing youths at further risk for engaging in drug use and other risk behaviors [e. The underlying mechanism reflects a hyperactive subcortical system and an underdeveloped PFC.
This model describes how drug craving leads to increased activation in subcortical regions specifically the ventral striatum and amygdala , and opportunities for regulation of the experience of craving and associated negative affect can come either from the PFC or from the direct effects of drug use. In cases where the PFC is less effectively able to regulate, as is the case for those with SUDs, drug use may be the selected way to cope with and regulate distress. Further, substance abusers are more likely to have greater sensitization and dysfunctional limbic system responses to negative affect and also exhibit greater connectivity between the limbic and PFC regions during emotional processing, but lower levels of connectivity during cognitive reappraisal and regulation tasks, indicative of poorer regulation of negative emotional experiences and less effective cognitive control [ 70 ].
Indeed, elevated limbic system response and activity in the amygdala and ventral striatum, combined with decreased regulatory response of the PFC, define the emotion regulation difficulties [e. Although core to both pathways, the manifestation of such emotion regulation deficits may be different e.
The externalizing pathway to SUDs is a well-known developmental theory which posits that behavioral disinhibition , undercontrol, and poor regulation in early childhood underlie risk across development, manifesting as comorbid externalizing and SUDs over time [ 80 , 81 ]. In this developmental trajectory, childhood impulsivity and behavioral disinhibition predict disruptive behavior disorders and increased externalizing symptoms in adolescence, which is further exacerbated by environmental risk, ultimately leading to comorbid externalizing and SUDs into adulthood [ 80 ].
The externalizing pathway highlights the underlying neurological systems of increased reward sensitivity and reactivity combined with decreased effortful control and regulation that are imbalanced and competing during adolescence i. This hyperactive affective response to reward cues combined with poor regulation and compromised executive functioning is associated with risk for comorbid SUDs and externalizing symptoms, including conduct disorder [e. Findings show that PFC functioning is impaired among youths with disruptive behavior disorders and SUDs, particularly leading to impairment of decision making in the context of tempting rewards [ 84 ].
Compared to healthy controls, youths with externalizing disorders also exhibit smaller PFC and amygdala volumes, indicating more disinhibited behavior and poorer regulation [ 84 , 85 , 86 ]. Although patterns of increased reward sensitivity and poor regulation of affective responses to rewards are evidenced in many studies, there have been mixed findings among youths with disruptive behavior disorders, with results showing either more or less reactive amygdala responses among these youths [ 84 ].
Part of what might explain these differences comes from work suggesting that youths with disruptive behavior disorders may actually show lower neural sensitivity to rewards, leading them to engage in more sensation-seeking and reward-seeking behavior to compensate for this lack of sensitivity see [ 84 ] for a review. Indeed, compared to a community control group of boys, adolescent boys diagnosed with comorbid conduct and substance use disorders exhibited hypoactivation in a number of brain regions comprising the limbic—striatal system including the amygdala and PFC regions during a risky decision making task with the possibility of gaining rewards [ 87 ].
The boys with comorbid psychopathology also showed hypoactivation in response to rewards, consistent with reward insensitivity. Smaller amygdala volumes have been found among youths with disruptive behavior disorders which could also contribute to findings showing diminished reward sensitivity among these youths [ 84 , 85 , 86 ].
Differences in reactivity across these brain regions may depend on several factors, including the particular neurological system and circuit of study, the specific lab-based task, and the specific externalizing disorder, a clear direction for future research efforts. A behaviorally inhibited temperamental style can be conceptualized as a form of emotional dysregulation.
Behavioral inhibition is characterized by a heightened startle and stress response, elevated response to novelty, negative emotionality, physiological dysregulation, attentional bias toward threat, misinterpretation of neutral cues as threatening, social reticence, and social skill deficits [e. The biological and behavioral correlates of behavioral inhibition are relatively stable and predict increased risk for internalizing disorders [ 90 ] and substance use over time [ 89 ].
Furthermore, behavioral inhibition interacts with risk-taking propensity, such that increased behavioral inhibition is associated with substance-related problems specifically among youths with high levels of risk-taking propensity [ 89 ]. Behavioral inhibition is also implicated in the underlying mechanisms linking emotion regulation to comorbid psychopathology via social skill impairment in childhood.
For children with highly inhibited temperamental styles, behavioral inhibition at ages 2—3 predicts more compromised emotion regulation abilities at age 5, which subsequently predicts more impaired social skills at age 7 [ 91 ]. Early social skill deficits are implicated as a continued risk factor propelling youths along the internalizing pathway to comorbid affective disorders and SUDs [ 82 ], and thus behavioral inhibition and corresponding difficulty with emotion regulation deficits in childhood serve as an early embedded risk underlying the internalizing pathway.
The core neurobiological regulation system we have highlighted throughout this review is implicated in the risk for internalizing and SUDs as well, and maps onto the temperamental features of behavioral inhibition over time [ 92 ]. Highly inhibited children at age 5 show greater right orbitofrontal cortex and amygdala volume at age 15, consistent with models of over-regulation and inhibition [ 85 ]. Robust findings also show that behaviorally inhibited children and those with anxiety disorders show a hyperactive amygdala response to threat [ 90 , 93 ], and adolescents with internalizing disorders generally show greater activity in both the amygdala and PFC regions in response to emotionally-salient stimuli [ 94 ].
The link between this heightened emotional response to threat and poor emotion regulation further increases risk for comorbid internalizing and substance use disorders. In contexts of heightened emotional stress and dysregulated states, individuals with comorbid internalizing and substance use disorders may be more likely drawn to drugs as a means to cope, which not only limits learning of effective emotion regulation and coping strategies, but also further reinforces addictive behaviors.
The genetics of addiction—a translational perspective | Translational Psychiatry
Support for this has been found among individuals diagnosed with comorbid PTSD and cocaine dependence who demonstrate an attentional bias toward drug cues specifically when prompted with an emotionally threatening stimulus involving a personal trauma script exposure [ 96 ]. Collectively, this pattern of results maps on to the risk trajectory outlined in the internalizing pathway [ 82 ]. Indeed, for youths with a history of early behavioral inhibition, emotion regulation difficulties, social skill deficits, and poor coping strategies, drug use may serve as a source of regulation and means to cope particularly in contexts of elevated threat and stress, ultimately leading to comorbid affective and substance use disorders later in development.
More advanced mapping of the neurobiological risk factors underlying this developmental pathway is an area for future research efforts. Although the scope of this report allows only a targeted review of the link between emotion regulation deficits and risk for comorbid psychopathology in adolescence, the extant literature indicates that emotion regulation is indeed a core transdiagnostic risk factor that represents early embedded risk for the development of substance use, addiction, and comorbid psychopathology.
Deficits in emotion regulation emerge during adolescence in part due to the dual systems model of imbalanced neurological development between the response and regulation systems, a risk process which is then exacerbated in contexts where the same response and regulation system malfunctions in various ways that can lead to multiple forms of psychopathology.
Collectively, this area of research indicates that emotion regulation is a key treatment target for intervention and prevention efforts focused on minimizing psychopathology risk. In addition to supporting individual emotion regulation development and strategies, this work also suggests that minimizing contextual stressors and environmental risk will be critical as well—stressors that we know further compromise emotion regulation abilities e.
We note that this review was intentionally limited in scope, leaving many other considerations that must be addressed in the discussion of a topic as large as the risk and development of comorbid psychopathology. Additional factors that must be considered include, but are not limited to, genetic risk, environmental risk, contextual stressors and trauma, parental psychopathology and substance use, and peer influences, with all of these factors interacting with emotion regulation to predict outcomes.
Consistent with the frameworks of developmental psychopathology and developmental science [ 16 , 98 , 99 ], we recognize that these complex developmental risk mechanisms must consider transactional processes across multiple levels of analysis e. This leaves significant work for future research efforts to continue identifying transdiagnostic risk processes, such as emotion regulation, and examining how these transdiagnostic processes interact with each other over time. These efforts will require a focus on developmental pathways themselves as the outcomes of interest, moving away from a simpler variable-focused approach.
A clear next step for future research on the topic of addiction and comorbid psychopathology will be to examine how these early developmental risk processes relate to the intergenerational transmission of emotion regulation deficits, addiction, and psychopathology risk. An extensive review of the unique and interactive functions across neurobiological regions is beyond the scope of this brief report, and thus we highlight several specific and robust examples in which emotion regulation difficulties manifest as neurobiological differences and help explain risk for comorbid disorders among youths.
We refer the reader elsewhere for more extensive and detailed accounts of neural circuits and functions related to psychopathology [e. However, we note that patterns of developmental trajectories of risky decision making may depend on the methodology employed, with a recent meta-analysis [ 44 ] showing that when completing behavioral lab-based tasks, adolescents take more risks than adults as expected , but are comparable, or in some cases, less risky than children contrary to the expected curvilinear trajectory over time , whereas real-world behavioral measures show that adolescents take more risks than both children and adults.
Determining why we observe curvilinear versus linear trajectories in risky decision making across development as a function of methodology is an area for future research. In either case, however, regulation and self-control are not fully developed until adulthood, and adolescence—as compared to childhood—is a period of heightened risk due to increased opportunities and exposure to contexts of drug use and other risky behaviors e.
Julia M. Shadur and Carl W. Lejuez declare that they have no conflict of interest.
Scope and Format
This article does not contain any studies with animal subjects performed by any of the authors. Skip to main content Skip to sections. Advertisement Hide. Download PDF. Part of the following topical collections: Topical Collection on Transgenerational Considerations in Addictions. Adolescence as a Critical Developmental Period Adolescents are particularly vulnerable to emotion regulation difficulties.
Neurobiology of Emotion Regulation Deficits underlying Risk for Addiction The dual systems model highlights how emotion regulation difficulties, reward-seeking, sensation-seeking, and impulsivity increase during adolescence, placing youths at further risk for engaging in drug use and other risk behaviors [e. The Externalizing Pathway to Substance Use Disorders The externalizing pathway to SUDs is a well-known developmental theory which posits that behavioral disinhibition , undercontrol, and poor regulation in early childhood underlie risk across development, manifesting as comorbid externalizing and SUDs over time [ 80 , 81 ].
Conflict of Interest Julia M. Adolescent substance use disorders: epidemiology, neurobiology, and screening. The American Psychiatric Publishing textbook of substance abuse treatment. Arlington: American Psychiatric Publishing, Inc. Google Scholar. Monitoring the future national results on drug use: — overview, key findings on adolescent drug use.
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