ReviewDevelopmental sources of variation in liability to adolescent substance use disorders
Introduction
Behavior during adolescence sets the stage for patterns of substance use and developmental trajectories toward substance use disorders (SUD). Prior to adolescence, few individuals have significant substance use, even within high-risk populations (Clark et al., 1998a). Among high-school seniors in the United States, 62% experience alcohol intoxication, and 49% try marijuana (Johnston et al., 1999). For adolescents who continue to use drugs, consumption generally progresses from legal compounds (e.g. tobacco and alcohol), to marijuana, and then to other illicit agents (Kandel et al., 1992, Anthony and Petronis, 1995, Martin et al., 1996). Unfortunately, very little is known regarding the timing and patterning of factors modulating escalation from substance use to SUD. The associated impairment resulting from progression of drug consumption underscores the importance of understanding the etiology of SUD from a biopsychosocial developmental perspective.
Many pathways to SUD are possible. This review examines the trajectories of a subgroup of youths at very high risk. These individuals are often characterized by early or late puberty compared to same age peers; affective, cognitive, and behavioral dysregulation; and possibly neuroadaptive changes. A theory is presented wherein the three components of dysregulation interact with family and peer factors as well as pubertal timing, leading to substance use. Continued exacerbation of affective, cognitive, and behavioral dysregulation by accumulating drug and non-drug stressors during late adolescence is posited to lead to neuroadaptations that increase the likelihood of developing SUD, particularly in high-risk individuals.
A central thesis is that when maturational dyssynchrony (e.g. incongruity in timing and sequencing among hormonal, physical, psychological, and social processes) occurs during late childhood and early adolescence, homeostatic activity of the hypothalamic–pituitary–adrenocortical (HPA) axis, the hypothalamic–gonadal (HPG) axis, and the mesotelencephalic dopaminergic pathways is perturbed. These changes are posited to influence both the timing of puberty and brain reward mechanisms, thereby increasing the risk for substance use. Said differently, incongruity of timing and sequencing among the above developmental processes produces ‘stress,’ which is a state of threatened homeostasis requiring psychological, physiological, and behavioral adaptation, including coping responses (see reviews in Johnson et al., 1992, Kreek and Koob, 1998). These accumulating pharmacological and non-pharmacological stressors occurring in late adolescence are thought to further increase the risk for SUD by young adulthood.
Section snippets
Definition of liability
Falconer defined liability as “…intended to express not only the individual innate tendency to develop or contract the disease, i.e. his or her susceptibility in the usual sense, but also the whole combination of external circumstances that make him more or less likely to develop the disease” (Falconer, 1965; p. 52). Phenotypic values above a diagnostic threshold on a normal distribution of liability phenotypes meet criteria for SUD (DSM-IV, American Psychiatric Association, 1994).
Liability to
A proposed phenotype: affective, cognitive, and behavioral dysregulation
A core disorder of self-regulation parsimoniously captures many of the traits increasing the risk for adolescent substance use in sons of SUD fathers (Martin et al., 1994, Dawes et al., 1997) and in twins with early onset SUD (Iacono et al., 1999). Dysregulation, with affective, cognitive, and behavioral components, is defined as a deficiency in the degree to which an individual can modulate his or her reactivity to environmental challenges. The prefrontal cortex is regarded as the primary
Stress-induced neuroadaptation and dysregulation of brain reward mechanisms
Adolescents who develop SUD, compared to adults with SUD, typically report a shorter time from first drug use to physical dependence (Clark et al., 1998b). Very little is known, however, regarding the progression of neuroadaptive changes underlying the transition from substance use to SUD in adolescence. Tolerance, craving, and withdrawal are thought to be less common and in most instances less severe in adolescence than in adulthood (Kaminer, 1994). A wealth of animal and limited clinical
Research implications
The available data on the sources of variation leading to adolescent SUD have implications for etiologic research. Future longitudinal studies should include assessment using multiple measures of the following factors: affective, cognitive, and behavioral dysregulation; the relationship of the three components of dysregulation to psychiatric comorbidity and current substance use; the severity, timing, and chronicity of environmental context and stressors; and somatic and pubertal maturation.
Acknowledgements
The Center for Education and Drug Abuse Research (CEDAR), University of Pittsburgh is a consortium between University of Pittsburgh and Saint Francis Medical Center. This work was supported in part by a Mentored Clinical Scientist Development Award (1K08 DA-299) to Dr Dawes, an Independent Scientist Award to Dr Clark (K02 AA00291), and by a Center grant (DA-05605) from the National Institute on Drug Abuse.
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