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Alterations in brain structure and functional connectivity in prescription opioid-dependent patients.

A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.

Pubmed ID: 20558415


  • Upadhyay J
  • Maleki N
  • Potter J
  • Elman I
  • Rudrauf D
  • Knudsen J
  • Wallin D
  • Pendse G
  • McDonald L
  • Griffin M
  • Anderson J
  • Nutile L
  • Renshaw P
  • Weiss R
  • Becerra L
  • Borsook D


Brain : a journal of neurology

Publication Data

July 29, 2010

Associated Grants

  • Agency: NIDA NIH HHS, Id: K24 DA022288
  • Agency: NIDA NIH HHS, Id: K24 DA022288
  • Agency: NINDS NIH HHS, Id: K24 NS064050
  • Agency: NIDA NIH HHS, Id: U10DA015831

Mesh Terms

  • Adolescent
  • Adult
  • Amygdala
  • Analgesics, Opioid
  • Brain
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Net
  • Neural Pathways
  • Opioid-Related Disorders
  • Young Adult