Etiology and Pathophysiology - General Approaches to Substance and Polydrug Use Disorders

Etiology and Pathophysiology

The cause of substance addiction depends on a variety of biological, psychological and social factors. Biological factors can include genetic predisposition as well as neurobiological substrates for positive and negative reinforcement by abused substances (Nestler, 2000). Family genetic studies have found rates of substance dependence three to four times higher in iden-tical twins than in dizygotic twins (Cloninger, 1999). Although no single biological marker or specific genetic defect has been confirmed, work has suggested that some alleles associated with variations in the dopamine receptor may be more common in substance-dependent individuals than in those who are not de-pendent. Similarly, risk factor studies have found that the sons of individuals suffering from alcoholism have a general hypore-sponsiveness to alcohol and sedative drugs, when compared with the sons of individuals without alcoholism.

Psychological factors related to etiology include high rates of depressive disorders and sensation seeking, which are found in substance addiction. The association of sensation seeking with substance addiction suggests not only that drugs enhance pleasant sensations, such as a high, but also that abused drugs may provide potential control of aggressive impulses. Whether abused drugsserve as self-medication for individuals with these psychologi-cal disturbances (e.g., depression and impulsivity) has not been resolved clearly because the age at onset for major psychiatric disorders, such as depression, is older than the age at onset for substance abuse and dependence (Khantzian, 1985). Childhood precursors of substance abuse and dependence, including shy and aggressive behaviors, can also be precursors of later depressive disorders as well as of antisocial personality disorder – the adult expression of aggressive impulsivity.

Finally, social factors, including peer and family influences, which are not dependent on genetic inheritance, are important in leading to initial drug exposure. Kandel (1975) has conducted longitudinal studies of “gateway drug” usage by adolescents, and these original concepts have been expanded over the last 25 years to recognize their treatment implications. These gateway drugs are tobacco, alcohol and marijuana. Adolescents who be-gin using gateway drugs in their early teens are more likely to have substance dependence in their twenties than are adolescents who begin use in their late teens. Delaying the initiation of these gateway drugs and their associated intoxication by 1 to 2 years substantially decreases the later risk of the development of sub-stance dependence. This association between early gateway drug use and later dependence may be related to the relatively higher rates of conduct disorder and failure to complete school in those who acquire a substance-related disorder in early adolescence. Life stressors related to peers and family are also possible causa-tive factors in substance dependence and their associated comor-bid psychiatric disorders.