Evidence-Based Reviews

Emerging clues: Is this teen at risk for substance abuse?

Current Psychiatry. 2009 January;8(1):19-27

Childhood characteristics may be predictive and suggest early interventions

References

1. Vanyukov MM, Tarter RE, Kirisci L, et al. Liability to substance use disorders: 1. Common mechanisms and manifestations. Neurosci Biobehav Rev. 2003;27(6):507-515.

2. Karpyak VM, Hall-Flavin DK, Mrazek DA. Can genetics predict risk for alcohol dependence? Current Psychiatry. 2008;7(3):57-73.

3. Kuo PH, Kalsi G, Prescott CA, et al. Association of ADH and ALDH genes with alcohol dependence in the Irish Affected Sib Pair Study of alcohol dependence (IASPSAD) sample. Alcohol Clin Exp Res. 2008;32(5):785-795.

4. Vanyukov MM, Maher BS, Devlin B, et al. The MAOA promoter polymorphism, disruptive behavior disorders, and early onset substance use disorder: gene-environment interaction. Psychiatr Genet. 2007;17(6):323-332.

5. Clark DB, Thatcher DL, Tapert S. Alcohol, psychological dysregulation and adolescent brain development. Alcohol Clin Exp Res. 2008;32(3):375-385.

6. Kendler KS, Schmitt E, Aggen SH, et al. Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry. 2008;65(6):674-682.

7. Sher KJ, Gershuny BS, Peterson L, et al. The role of childhood stressors in the intergenerational transmission of alcohol use disorders. J Stud Alcohol. 1997;58:414-427.

8. Clark DB, De Bellis MD, Lynch KG, et al. Physical and sexual abuse, depression and alcohol use disorders in adolescents. Drug Alcohol Depend. 2003;69(1):51-60.

9. Clark DB, Thatcher DL, Maisto S. Adolescent neglect and alcohol use disorders in two-parent families. Child Maltreat. 2004;9(4):357-370.

10. Clark DB, Kirisci L, Mezzich A, et al. Parental supervision and alcohol use in early adolescence: developmentally specific interactions. J Dev Behav Pediatr. 2008;29(4):285-292.

11. Clark DB, Kirisci L, Moss HB. Early adolescent gateway drug use in sons of fathers with substance use disorders. Addict Behav. 1998;23:561-566.

12. Clark DB, Winters KC. Measuring risks and outcomes in substance use disorders prevention research. J Consult Clin Psychol. 2002;70(6):1207-1223.

13. Clark DB, Cornelius JR, Wood DS, et al. Psychopathology risk transmission in children of parents with substance use disorders. Am J Psychiatry. 2004;161(4):685-691.

14. Guy SC, Isquith PK, Gioia GA. Behavior rating inventory of executive function—self-report version professional manual. Lutz, FL: Psychological Assessment Resources; 2004.

15. Clark DB, Cornelius JR, Kirisci L, et al. Childhood risk categories for adolescent substance involvement: a general liability typology. Drug Alcohol Depend. 2005;77(1):13-21.

16. Clark DB. The natural history of adolescent alcohol use disorders. Addiction. 2004;99(suppl 2):5-22.

17. Donovan JE, Molina BS. Children’s introduction to alcohol use: sips and tastes. Alcohol Clin Exp Res. 2008;32(1):108-119.

18. Clark DB, Chung T, Martin CS. Alcohol use frequency as a screen for alcohol use disorders in adolescents. Int J Adolesc Med Health. 2006;18(1):181-187.

19. Tarter RE, Kirisci L, Mezzich A, et al. Neurobehavioral disinhibition in childhood predicts early age onset substance use disorder. Am J Psychiatry. 2003;160(6):1078-1085.

20. Tarter RE, Vanyukov M, Kirisci L, et al. Predictors of marijuana use in adolescents before and after licit drug use: examination of the gateway hypothesis. Am J Psychiatry. 2006;163(12):2134-2140.

21. Clark DB, Bukstein OG, Smith MG, et al. Identifying anxiety disorders in adolescents hospitalized for alcohol abuse or dependence. Psychiatr Serv. 1995;46:618-620.

22. Spoth R, Greenberg M, Turrisi R. Preventive interventions addressing underage drinking: state of the evidence and steps toward public health impact. Pediatrics. 2008;121(suppl 4):S311-336.

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Traditionally, clinicians have identified children at high risk for substance abuse disorders (SUDs) by their family history—such as “children of alcoholics.” Advances in etiology research, however, have led to the identification of other risks for SUDs seen during childhood (Table). The clustering of these SUD risk factors—genetic influences, family characteristics, and predictive phenotypes—makes it feasible to identify children and adolescents who are very likely to develop problematic substance use.

Table

Risk factors for substance abuse in children and adolescents

Genetic predisposition
Parental substance use
Maltreatment
Inadequate supervision
Impulsive behavior, inattention, irritability
Substance availability
Early substance use

Nature vs nurture

Genetic influences. Heritable risk accounts for a substantial proportion of the variation in SUDs, as multiple genes differentially influence substance initiation, metabolism, and reinforcing properties.¹ For example, well-characterized genetic variations determine individual differences in alcohol dehydrogenase and aldehyde dehydrogenase—the enzymes involved in alcohol metabolism—and influence liability to alcohol use disorders (AUDs).^2,3 Researchers are exploring ways in which genes might impact SUD risk (Box 1).^1,4,5

Genetic influences on substance use may be less important during adolescence than adulthood. In a study of 1,796 male twins’ alcohol, nicotine, and cannabis use from early adolescence to middle adulthood, genetic variations had little or no influence on substance use in early adolescence. The influence of genetic factors gradually increased with age.⁶

Familial environmental factors, by contrast, were important in early adolescence and gradually decreased in effect with increasing age. During adolescence, the family’s influence on substance use apparently operates more through environmental characteristics than through heritable factors.⁶

Familial influences. Parents with ongoing SUDs model problematic substance use and create environments of child maltreatment and inadequate supervision.

Child maltreatment. Children of parents with SUDs are more likely to suffer sexual abuse, physical abuse, or neglect.⁷ The effects of sexual abuse on the child may vary by abuse severity and the child’s gender, developmental stage, and relationship to the perpetrator. Maltreatment may cause the child difficulties in psychological regulation and social development, leading to related psychopathology; these characteristics may contribute to later SUDs.⁸

Inadequate supervision. Adolescents who report that their parents do not effectively monitor their activities have an increased likelihood of developing SUDs. However, children/adolescents who exhibit difficulties with psychological regulation—such as impulsive behavior and irritability—are difficult to parent, and adolescents with early substance involvement may subvert parental supervision efforts.^9,10

Box 1

Can genes predict substance abuse risk?

Recent investigations have examined genes that might confer risk across substance types. Promising research has focused on:

genes that influence functional variations in neurotransmitter systems
gene-environment interactions
the search for neurobiological endophenotypes—characteristics that cannot be observed by conventional means, such as brain development characteristics that are seen through neuroimaging.^1,4,5

Specific molecular-level genetic variations can be measured in individual patients but cannot yet validly quantify risk.

Predictive phenotypes

Predictive phenotypes—measurable individual characteristics that predict SUDs—may be considered risk factors but should not be viewed as causal influences akin to genetic and familial/environmental factors. Rather, predictive phenotypes may reflect propensities that are manifested by specific behaviors and other features according to developmental stage and environmental facilitation.

Clinical Point

Family factors that influence substance use include child maltreatment and inadequate supervision

In other words, predictive phenotypes are observable childhood characteristics with systematic patterns over the course of development that predict SUDs. Not coincidently, these predictive phenotypes are caused by many of the same genetic and environmental influences that cause SUDs. Phenotypes predicting SUDs include:

specific psychiatric disorders
specific personality traits that collectively are called psychological dysregulation
early substance use.¹¹

Psychopathology. Childhood psychopathologies that predict SUDs include conduct disorder (CD), attention-deficit/hyperactivity disorder (ADHD), mood disorders, and posttraumatic stress disorder (PTSD).¹² These disorders are transmitted from parent to child in a developmentally specific fashion¹³ and cluster in high-risk children and adolescents.

Recent studies have demonstrated that this clustering of problems—including impulsive behavior, inattention, and negative affect—represents a single continuous dimension termed psychological dysregulation.¹² The construct of psychological dysregulation has origins in neuropathology and provides a conceptual link between childhood psychopathological characteristics known to predict SUD and neurobiological deficits.⁵ Childhood indices of psychological dysregulation—such as the Behavior Rating Inventory of Executive Function (BRIEF)¹⁴—complement other risk factors, such as parental SUDs and early substance use, in predicting accelerated substance use and SUDs.¹⁵

Neurobiological characteristics. Recent investigations have focused on relationships between variations in normal brain development and differences in psychological regulation.⁵ Several brain structures thought relevant to the development of psychological regulation—including the prefrontal cortex, limbic structures, and reward circuits—develop during adolescence. Delays or deficits in the development of these structures are called neurodevelopmental dysmaturation.⁵

Variation in genes that influence these brain areas may interact with environmental influences—including child maltreatment and early substance use—to produce neurodevelopmental dysmaturation that manifests as psychological dysregulation. Thus, genetic and environmental causes are hypothesized to lead to an endophenotype (neurodevelopmental dysmaturation) and developmentally specific phenotypes, such as: