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

Abstract

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.

Major Depressive Disorder and Heroin-dependent Patients Share Decreased Frontal Gray Matter Volumes: A Voxel-Based Morphometry Study

“…These support our hypothesis that heroin-dependent and major depression subjects have shared frontal GMV alterations compared to health controls. The present findings also are consistent with other structural and functional neuroimaging studies which found disruptions of the frontal cortex in individuals with repeated drug abuse including heroin-dependence (Upadhyay et al, 2010;Vasic, Walter, Hose & Wolf, 2008;Verdejo-Garcia, Rivas-Perez, Lopez-Torrecillas & Perez-Garcia, 2006). …”

Identification of a Dopamine Receptor-Mediated Opiate Reward Memory Switch in the Basolateral Amygdala–Nucleus Accumbens Circuit

“…Emerging evidence implicates the importance of the BLA3 NAc circuit in the opiate addiction process (Frenois et al, 2005;Upadhyay et al, 2010;Xie et al, 2011). Opiate dependence and withdrawal are associated with structural and functional abnormalities in the amygdala of abstinent opiate-dependent patients and disturbed functional connectivity between the amygdala and associated pathways, including the PFC and NAc (Upadhyay et al, 2010).…”

“…Opiate dependence and withdrawal are associated with structural and functional abnormalities in the amygdala of abstinent opiate-dependent patients and disturbed functional connectivity between the amygdala and associated pathways, including the PFC and NAc (Upadhyay et al, 2010). Previous reports demonstrate an important role for intra-BLA DA transmission during the processing of drug-related reward learning and relapse-related phenomena.…”

Fentanyl dependence associated with the use of transdermal fentanyl in a cancer patient: a case report

“…Loss of volume in the amygdala, white matter anisotropy in the afferent and efferent pathways of the amygdala and a decrease in functional connections in the amygdala have been determined in individuals prescribed long-term opioid for therapeutic reasons (14). These findings are clinically important in terms of showing functional changes in regions of the brain associated with motivation and reward functions, impulse control and affect regulation in individuals prescribed long-term opioid.…”