Progressive White Matter Microstructure Damage in Male Chronic Heroin Dependent Individuals: A DTI and TBSS Study

Abstract

BackgroundTo investigate the WM microstructure deficits in heroin dependent individuals (HDIs) with different length of heroin dependence, and to investigate whether these WM deficits can be related to the duration of heroin use and to decision-making deficits in HDIs.Methodology/Principal FindingsThirty-six HDIs [including eighteen sHDIs (duration of heroin dependent is less than 10 years) and eighteen lHDIs (duration of dependent is between 10∼20 years)] and sixteen healthy controls participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) were performed by tract-based spatial statistics (TBSS) to localize abnormal WM regions among groups. TBSS demonstrated that sHDIs had significantly lower FA than controls in right orbito-frontal WM, bilateral temporal WM and right parietal WM. The lHDIs had significantly lower FA throughout the brain compared with the controls and sHDIs. The lHDIs had significantly lower Da than controls in bilateral inferior frontaloccipital fasciculus, bilateral splenium of corpus callosum, left inferior longitudinal fasciculus, and had significantly higher Dr than controls in bilateral uncinatus fasciculus, bilateral inferior frontaloccipital fasciculus and bilateral cortical spinal fasciculus. Volume-of-interest (VOI) analyses detect the changes of diffusivity indices in the regions with FA abnormalities revealed by control vs sHDIs. In most VOIs, FA reductions were caused by the increase in Dr as well as the decrease in Da. Correlation analysis was used to assess the relationship between FA and behavioral measures in HDIs and controls available. Significantly positively correlations were found between the FA values in the right orbital-frontal WM, right parietal WM and IGT performance.ConclusionsThe extent and severity of WM integrity deficits in HDIs was associated with the length of heroin dependent. Furthermore, abnormal WM microstructure may correlate with decision-making impairments in HDIs.

Structural brain markers are differentially associated with neurocognitive profiles in socially marginalized people with multimorbid illness.

“…Nevertheless, it is noteworthy that the pattern of differential diffusivities (more prominent increases in RD) has been frequently observed in clinical samples including substance use (Qiu et al, 2013;Willi et al, 2016), HIV infection (Leite et al, 2013), and related comorbid conditions (Tang et al, 2015). Collectively, this pattern is thought to be characteristic of chronic white matter degeneration (Burzynska et al, 2010).…”

“…For example, in schizophrenia patients, FA correlates with measures of verbal memory, attention, and executive functions in tracts specifically known to mediate these respective functions (Lim et al, 2006). Likewise, lower FA and higher diffusivity in frontal and parietal tracts has been linked with poorer performance on an affective decision-making task in cocaine-dependent (Lane et al, 2010) and heroin-dependent subjects (Qiu et al, 2013). On the other hand, when age and motor function were controlled for in cognitively normal adults, associations were identified between executive functioning, memory, and information processing, and white matter tract integrity in the corresponding functional regions (Sasson, Doniger, Pasternak, Tarrasch, & Assaf, 2012).…”

Structural imaging for addiction medicine

“…These studies find diminished white matter integrity in frontal, temporal, and parietal regions (Bora et al, 2012; Liu et al, 2008; Qiu et al, 2013), as well as specific tracts connecting neuronal regions (Upadhyay et al, 2010). Associations between duration of use and FA in these white matter regions have been observed such that the longer the duration of opioid abuse the more damage to the tissue.…”

“…Additionally, examination of white matter tracts has implicated a number of pathways where decreased FA in opiate abusers have been observed including the stria terminalis, ventral amygdalofugal fibers, and uncinuate fasciculus that connect the amygdala with other subcortical and cortical structures, including the nucleus accumbens and insula (Upadhyay et al, 2010). Some researchers have explained these white matter changes as damage to only myelin (Bora et al, 2012), whereas others have found evidence for both myelin pathology and axonal injury (Qiu et al, 2013), possibly due to opioid-induced leukoencephaly (Liu et al, 2008). There is also evidence for increased ischemic lesions in heroin abusers (Andersen and Skullerud, 1999), which may result from perfusion deficits and/or ischemia related to respiratory suppression, overdoses, disturbance of consciousness, vasculitis, and rhabdomyolosis in heroin abusers (Qiu et al, 2013).…”

“…Some researchers have explained these white matter changes as damage to only myelin (Bora et al, 2012), whereas others have found evidence for both myelin pathology and axonal injury (Qiu et al, 2013), possibly due to opioid-induced leukoencephaly (Liu et al, 2008). There is also evidence for increased ischemic lesions in heroin abusers (Andersen and Skullerud, 1999), which may result from perfusion deficits and/or ischemia related to respiratory suppression, overdoses, disturbance of consciousness, vasculitis, and rhabdomyolosis in heroin abusers (Qiu et al, 2013). White matter damage is not surprising given that cell types such as oligodendrocytes express opioid receptors and blocking opioid receptor activity alters myelin production.…”