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.