Michael Vanyukov

Etiology of early age onset substance use disorder: A maturational perspective

The etiology of early age onset substance use disorder (SUD), an Axis I psychiatric illness, is examined from the perspective of the multifactorial model of complex disorders. Beginning at conception, genetic and environment interactions produce a sequence of biobehavioral phenotypes during development which bias the ontogenetic pathway toward SUD. One pathway to SUD is theorized to emanate from a deviation in somatic and neurological maturation, which, in the context of adverse environments, predisposes to affective and behavioral dysregulation as the cardinal SUD liability-contributing phenotype. Dysregulation progresses via epigenesis from difficult temperament in infancy to conduct problems in childhood to substance use by early adolescence and to severe SUD by young adulthood.

Dopamine system genes and attention deficit hyperactivity disorder: A meta-analysis

The dopamine system may play a major role in the development of attention deficit hyperactivity disorder (ADHD). We applied a random-effects model meta-analysis to family-based studies of association between ADHD and the dopamine system genes DRD4, DRD5 and DAT1. A statistical test of heterogeneity was conducted for each group of studies. The meta-analysis of DRD4 included data from 13 studies, with a total of 571 informative meioses. The pooled odds ratio estimate was 1.41 (95% CI 1.20–1.64, P=1.57×10−5), demonstrating positive association. For DRD5, data from five studies, with a total of 340 informative meioses, were combined yielding a pooled odds ratio of 1.57 (95% CI 1.25–1.96, P=8.28×10−5). Eleven studies examining DAT1, with a total of 824 informative meioses, yielded a non-significant pooled odds ratio estimate of 1.27 (95% CI 0.99–1.63, P=0.06). There was no support of heterogeneity between the studies. Overall, the meta-analyses support the involvement of the dopamine system genes in ADHD liability variation and suggest the need for studies examining interactions between these genes.

Alcoholism: a developmental disorder.

Alcoholism etiology is discussed from a developmental behavior genetic perspective. At the outset point, temperament characteristics, by means of ongoing and reciprocal interaction with the social environment, shape the course of behavioral development. The behavioral characteristics successively acquired during development are vectors that determine the ontogenetic trajectory that culminates ultimately in the clinical disorder of alcoholism. The temperament features that appear to be associated with a heightened risk for alcoholism are examined. Their interactions with the environment during the course of development are considered within an epigenetic framework and, as discussed, have important ramification for improving the prevention and treatment of alcoholism.

Origins and consequences of child neglect in substance abuse families.

The empirical literature pertaining to the prevalence, origins, and consequences of neglectful parenting as it relates to substance abuse is critically reviewed. Available evidence indicates that children who experience parental neglect, with or without parental alcohol or drug abuse, are at high risk for substance use disorder (SUD). The effects of parental substance abuse on substance abuse outcome of their children appear to be partly mediated by their neglectful parenting. The discussion concludes with presentation of a developmental multifactorial model in which neglect, in conjunction with other individual and environmental factors, can be integratively investigated to quantify the childs overall liability across successive stages of development as well as to map the trajectory toward good and poor outcomes.

Liability to substance use disorders: 1. Common mechanisms and manifestations

Variation in the risk for and severity of substance use disorders (SUD) in the population is caused by multiple organismic (genetic, biochemical, psychological) and environmental factors. Whereas drug- or drug-class-specific liability mechanisms exist, a substantial proportion of variance in the risk is shared between specific liabilities, reflecting mechanisms that determine common liability to SUD. Data from epidemiologic, clinical, psychological, physiological, biochemical, and family and genetic studies reviewed in this paper indicate the existence of mechanisms and characteristics shared in common by liabilities to SUD related to different drugs. These mechanisms can be conceptualized as common liability to SUD, a latent trait accounting for a substantial portion of variation in SUD risk and severity and determined by all factors influencing the probability of SUD development. An accompanying paper describes an approach to the quantitative estimation of this trait.

Aggressivity, inattention, hyperactivity, and impulsivity in boys at high and low risk for substance abuse.

Aggressivity, inattention, hyperactivity, and impulsivity are cardinal dimensions of externalizing behavior problems of childhood. They are diagnostic and clinical features of childhood disorders, and are thought to be linked to the subsequent development of adult disorders such as substance abuse (SA). Little is known, however, about the convergent and discriminant validity of these four constructs. We used multiple measures to develop indices of aggressivity, inattention, hyperactivity, and impulsivity in a sample of 10- to 12-year-old boys (N=183) with and without a family history of SA. Data were taken from mother reports, child reports, teacher reports, and laboratory tasks. The study aims were (1) to test the convergent and discriminant validity of aggressivity, inattention, hyperactivity, and impulsivity; (2) to examine whether the data were consistent with a model specifying the four constructs as indicators of one superordinate factor; and (3) to differentiate boys with and without a family history of SA in construct scores. The results supported the convergent and discriminant validity of the four constructs. Although discriminable, the constructs covaried strongly and were consistent with a model specifying them as indicators of a single superordinate factor. Boys with a family history of substance abuse scored higher than control boys on aggressivity, inattention, and impulsivity scores, but the groups did not differ on hyperactivity scores. The results are discussed in terms of the role of childhood behavior problems in vulnerability to SA.

Genetic studies of substance abuse

Genetic studies of substance abuse indicate that variation in the risk for the disorder in the population is contributed by differences in both individual genotypes and environment. Recent developments in genetics raise the possibility of disentangling the complex system of genotype-environment interaction that determines the development of the individual behavioral phenotype. This paper reviews the concepts, methods and results pertaining to genetic investigation of substance abuse.

Developmental sources of variation in liability to adolescent substance use disorders

This review provides a synthesis of the literature on the complex sequence of maturational, psychosocial, and neuroadaptive processes that lead to substance use disorders (SUD) in adolescence. A brief overview introduces the concepts of liability to SUD and epigenesis. A theory is presented explaining how affective, cognitive, and behavioral dysregulation in late childhood is exacerbated during early and middle adolescence by family and peer factors, as well as puberty, leading to substance use. Continued exacerbation of the three components of dysregulation by drug and non-drug stressors during late adolescence is posited to result in neuroadaptations that increase the likelihood of developing SUD, particularly in high-risk individuals. Implications for etiologic research as well as clinical and preventive interventions are discussed.

Salivary cortisol responses in prepubertal boys: the effects of parental substance abuse and association with drug use behavior during adolescence

BACKGROUND The purpose of this investigation was three-fold. First, we extended our original observation of decreased cortisol reactivity to an anticipated stressor in sons of fathers with a substance use disorder (SUD). Second, we examined the hypothesis that salivary cortisol underresponsivity in these high-risk prepubertal boys is an adaptation to the stress associated with having a father with a current, rather than remitted, SUD. Third, we tested the hypothesis that prepubertal cortisol underreactivity might be associated with subsequent drug use behavior during adolescence. METHODS Preadolescent salivary cortisol responses were examined in the context of risk-group status, paternal substance abuse offsets, and subsequent adolescent drug use behavior. RESULTS The results confirmed a decreased salivary cortisol response to an anticipated stressor among sons of SUD fathers in our expanded sample. In addition, sons of fathers with a current SUD and boys whose fathers had a SUD offset from their 3rd to 6th birthdays had lower anticipatory stress cortisol levels compared with sons of control fathers. Finally, lower preadolescent anticipatory cortisol responses were associated with regular monthly cigarette smoking and regular monthly marijuana use during adolescence. CONCLUSIONS Hyporeactivity as an adaptation to chronic stress may be salient to the intergenerational transmission of substance abuse liability.

Mating assortment and the liability to substance abuse

Assortative mating can exert a profound influence on the phenotypic composition of the population since it may result in an increase in the frequency of the genotypes associated with extreme phenotypes. Applied to the risk for a disorder such as substance abuse, this would mean a possibility for an increase in the risk and severity of the disorder in consecutive generations. This paper reviews the theoretical and empirical literature on mechanisms related to mate resemblance for the liability to substance abuse, sources and consequences of such resemblance, and suggests directions for further research.