Date Published: October 24, 2013
Publisher: Public Library of Science
Author(s): Jaeuk Hwang, Jieun E. Kim, Marc J. Kaufman, Perry F. Renshaw, Sujung Yoon, Deborah A. Yurgelun-Todd, Yera Choi, Chansoo Jun, In Kyoon Lyoo, Grainne M. McAlonan.
Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP), a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.
The overall length of the CSP and the prevalence of abnormal enlargement of the CSP were assessed and compared in 65 opiate-dependent subjects (41 adolescent-onset opiate users and 24 adult-onset opiate users) and 67 healthy subjects.
Opiate-dependent subjects showed a greater prevalence of abnormal CSP enlargement relative to healthy subjects (odds ratio [OR]=3.64, p=0.034). The overall CSP length of adolescent-onset opiate-dependent subjects was greater, as compared not only with healthy subjects (F1,104=11.03, p=0.001) but also with those who began opiate use during adulthood (F1,61=4.43, p=0.039).
The current findings provide the first evidence that abnormal CSP enlargement, which reflects limbic system dysgenesis of neurodevelopmental origin, may be linked to later development of opiate dependence. In addition, a greater CSP length, which indicates more severe limbic abnormalities, appears to confer higher risk for earlier onset of opiate use.
An earlier onset of substance abuse particularly during adolescence has been suggested to be related to chronic relapsing medical course in adulthood [1,2]. As the long-lasting implications of adolescent-onset substance abuse draw more attention, researchers also seek potential neurobiological markers that may identify adolescent subgroups with high vulnerability to experimental use of illicit drugs and subsequent development of dependence on these drugs.
The present study provides the first in vivo human evidence that neurodevelopmental abnormalities of the limbic structures may be associated with subsequent and earlier development of opiate dependence. We found a greater prevalence of CSP enlargement in opiate-dependent subjects, which potentially represents limbic dysgenesis at early stages of development. As suggested by previous findings, the abundant expression of opioid receptors in the limbic system  may also account for the increased likelihood of opiate dependence in individuals with enlarged CSPs. Since other conditions that might elicit CSP abnormality, such as major comorbid psychiatric disorders with neurodevelopmental origin [13,16], were excluded from the study, it is unlikely that these potential confounding conditions had contributed to the present results.