Introduction

Relations between cognition and substance abuse in adolescence

A number of studies have indicated that specific aspects of cognitive function may play a role in risk of substance abuse in young people1. For example, studies have reported that children at high risk for substance abuse, who have not yet started using substances (for example, children of substance dependent parents) may have specific cognitive deficits, including lower academic achievement, lower verbal and visuospatial ability, and reduced attention span and executive function. These findings have been extended in adoption studies, in which cognitive impairments were found in children of substance abusing parents, even though these children were adopted at birth and raised in an environment without substance abuse. These findings suggest that potential cognitive impairments that may predispose to later substance abuse may have a biological component and can not be entirely explained by rearing circumstances. Tarter et al. (2004) have hypothesized that cognitive tasks tapping into prefrontal cortex (PFC) dysfunction in particular may contribute to the liability to substance dependence2. However, there is a lack of studies that examine the relationships between cognitive functioning and the development of substance involvement over time, and take account of the influences of other potentially important factors, such as a youngster's personality, behavioural problems and family-related factors.

Personality, behavioural problems and family-related factors

Certain aspects of personality, including impulsivity, sensation-seeking motivation and low locus of control, have been related to increased risk of substance abuse in adolescence. However, few studies have examined how personality and cognition may work in conjunction to increase adolescents' risk of substance abuse. One cross-sectional study, which was limited to girls, reported that personality (i.e., temperament) acted as a mediator in the relation between executive function and substance use in adolescence3. It is however, also conceivable that cognition can act as a mediator in the relationship between personality and risk of substance abuse. In further disentangling these relationships, a longitudinal study design would provide major advantages in resolving the temporal relationships between cognition, personality and the development of substance abuse. Another study found that specific combinations of cognitive impairment and personality (i.e., disinhibition) posed the greatest risk for the development of substance abuse4. It would be important to replicate these findings and extend them by also examining other personality traits, such as sensation seeking and low locus of control. Relationships could first be explored for each trait individually and subsequently for combinations of personality traits. Furthermore, it would be important to take into account other aspects of a youngster's behaviour such as symptoms of conduct disorder and attention-deficit-hyperactivity disorder.

Family-related factors can also play an important role in adolescent substance abuse. For example, it is relatively well-established that young people who have a poor relationship with their parents or are poorly monitored by their parents have increased risk of substance abuse5. Young people's family background can also influence cognitive function. For example, Silveri et al. (2004) reported that parental substance abuse has a pronounced impact on young people's emotional and cognitive development6. Yet, few studies have examined to what extent the relationship between substance abuse and cognitive function in adolescence is influenced by family factors.

Genetic influences

A large literature of family, adoption and twin studies has indicated that genetic influences play a role in substance use and abuse as well as in cognition. Specific genetic variants have been studied in relation to cognitive function and substance abuse. A considerable literature indicates that the neurotransmitter dopamine plays a role in many if not all addictive phenotypes7 as well as in cognitive processes mediated by the PFC8. There has been a flurry of studies examining the role of the COMT gene in executive function. COMT encodes the enzyme catechol-o-methyltransferase (COMT) and is critical for dopamine metabolism in the PFC. For example, a study based on children participating in the ALSPAC study found that the COMT Val158Met polymorphism was associated with IQ as well as executive function (particularly cognitive tasks tapping into PFC function)9, although the effects may be stronger for IQ than for certain specific cognitive tasks10. Studies to date, however, have not tended to take into account potential differences between tasks tapping into affective (or 'hot') versus non-emotional (or 'cold') cognitive processes11. Furthermore, findings to date have largely been limited to the COMT Val158Met polymorphism, while there is evidence that the study of COMT haplotypes may be more promising in accounting for phenotypic variability12;13.

COMT has also been associated with substance abuse, although there are negative findings as well14. Some of the discrepancy may be related to personality, for example, in a sample of polysubstance abusers, the Val158Met polymorphism was found to be associated with addiction through impulsivity or dyscontrol15. When explaining the relations between cognition and substance abuse it will be important to include genetic information. This will contribute towards clarification of these relations and may also provide some insight into the reasons for the underlying discrepancies in genetic studies of substance abuse.

Aims of the proposed study:

We propose to study the relations between cognition and substance use/abuse in a large and representative UK-based sample of adolescents. The specific aims are to:

1. Examine the relations between aspects of cognition, specifically IQ and PFC functioning, and the development of substance involvement over time;

2. Examine the influences of personality, problem behaviour and family-related factors (including relations with parents, parental monitoring and parental substance abuse) on these relationships;

3. Investigate whether genes that have been related to both cognition and substance abuse (e.g., COMT) moderate the association between both phenotypes.

Sample and statistical analysis

The Avon Longitudinal Study of Parents and Children (ALSPAC) is an ongoing UK-based longitudinal study, comprising 14,541 mothers recruited in 1991 who have been followed with their offspring from before birth up to age 16 (www.alspac.ac.uk). DNA samples are available for ~10,000 children and COMT has already been typed in this cohort. Typing of other genes that may play a role in the relationship between cognition and substance abuse is currently taking place.

We would be interested in studying the following variables:

Concept Person Source Timepoints

Substances

Alcohol use Child Child/ parent Childhood/ adolescence

Cigarette use Child Child/ parent Childhood/ adolescence

Cannabis use Child Child/ parent Childhood/ adolescence

Cognition

IQ Child Child Childhood/ adolescence

Verbal ability Child Child Childhood/ adolescence

Working memory Child Child Childhood

Attention Child Clinic Childhood/ adolescence

Executive function Child Clinic Childhood/ adolescence

Inhibition/ impulsivity Child Clinic Childhood/ adolescence

Mediating/ moderating factors

Personality

Temperament Child Parent Childhood

Sensation seeking Child Child Adolescence

Locus of control Child Child Childhood/ adolescence

Family-related variables

Parental substance abuse Parent Parent Childhood/ adolescence

Parent-child relations Child/ Parent Parent/ child Childhood/ adolescence

Parental monitoring Parent Parent/ child Childhood/ adolescence

Child problem behaviour

Conduct problems Child Parent/ child Childhood/ adolescence

Attention-Deficit- Child Parent/ child Childhood/ adolescence

Hyparactivity Problems

Genetic influences

COMT Child

Relations between variables will be evaluated using linear/ logistic regression analysis and path analysis. Latent class analyses will be used to define clusters of cognitive and other variables with different predictive relationships with substance abuse. Latent growth curve modelling will allow the study of predictors of change and individual trajectories over time.

References

1. N. Z. Weinberg, J Am Acad Child Adolesc Psychiatry 36, 1177-86 (1997).

2. R. E. Tarter, L. Kirisci, M. Habeych, M. Reynolds, M. Vanyukov, Drug Alcohol Depend 73, 121-32 (2004).

3. P. R. Giancola and A. C. Mezzich, J Child Psychol Psychiatry 44, 857-66 (2003).

4. L. Kirisci, R. E. Tarter, M. Vanyukov, M. Reynolds, M. Habeych, Drug Alcohol Depend 76, 125-33 (2004).

5. K. H. Shelton et al., (In Press (J Youth Adolesc)).

6. M. M. Silveri , G. K. Tzilos, P. J. Pimentel, D. A. Yurgelun-Todd, Ann N Y Acad Sci 1021, 363-70 (2004).

7. A. I. Leshner and G. F. Koob, Proc Assoc Am Physicians 111, 99-108 (1999).

8. E. M. Tunbridge, P. J. Harrison, D. R. Weinberger, Biol Psychiatry 60, 141-51 (2006).

9. J. H. Barnett et al., Am J Psychiatry 164, 142-9 (2007).

10. J. H. Barnett, L. Scoriels, M. R. Munafo, Biol Psychiatry 64, 137-44 (2008).

11. A. Kerr and P. D. Zelazo, Brain Cogn 55, 148-57 (2004).

12. S. Shifman et al., Am J Hum Genet 71, (2002).

13. A. G. Nackley et al., Science 314, 1930-3 (2006).

14. M. B. van den Bree, Curr Psychiatry Rep 7, 125-32 (2005).

15. D. J. Vandenbergh, L. A. Rodriguez, I. T. Miller, G. R. Uhl, H. M. Lachman, Am J Med Genet 74, 439-42 (1997).