White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances

Kaag, Anne Marije; Wingen, Guido van; Caan, Matthan W.A.; Homberg, Judith R.; Brink, Wim van den; Reneman, Liesbeth

doi:10.1111/adb.12375

Cited by 37 publications

(28 citation statements)

References 45 publications

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“…Several of the prior studies that found cocaine effects on white matter integrity permitted other drug use, including opiate and sedative use disorders, in their cocaine-using groups (Lane et al , 2010; Lim et al , 2002; Lim et al , 2008; Ma et al , 2009; Moeller et al , 2005; Moeller et al , 2007). A recent study found that FA reduction correlated negatively with number of substances used (Kaag et al , 2016). Thus, it is possible that prior findings reflected the broader effects of poly-substance use on white matter, rather than the specific effects of cocaine.…”

Section: Discussionmentioning

confidence: 99%

Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection

et al. 2017

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This study investigated the association of HIV infection and cocaine dependence with cerebral white matter integrity using diffusion tensor imaging (DTI). 135 participants stratified by HIV and cocaine status (26 HIV+/COC+, 37 HIV+/COC−, 37 HIV−/COC+, and 35 HIV−/COC−) completed a comprehensive substance abuse assessment, neuropsychological testing, and MRI with DTI. Among HIV+ participants, all were receiving HIV care and 46% had an AIDS diagnosis. All COC+ participants were current users and met criteria for cocaine use disorder. We used tract-based spatial statistics (TBSS) to assess the relation of HIV and cocaine to fractional anisotropy (FA) and mean diffusivity (MD). In whole-brain analyses, HIV+ participants had significantly reduced FA and increased MD compared to HIV− participants. The relation of HIV and FA was widespread throughout the brain, whereas the HIV-related MD effects were restricted to the corpus callosum and thalamus. There were no significant cocaine or HIV-by-cocaine effects. These DTI metrics correlated significantly with duration of HIV disease, nadir CD4+ cell count, and AIDS diagnosis, as well as some measures of neuropsychological functioning. These results suggest that HIV is related to white matter integrity throughout the brain, and that HIV-related effects are more pronounced with increasing duration of infection and greater immune compromise. We found no evidence for independent effects of cocaine dependence on white matter integrity, and cocaine dependence did not appear to exacerbate the effects of HIV.

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Section: Discussionmentioning

confidence: 99%

Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection

et al. 2017

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“…Due to incidental finding of a brain abnormality (N=1), and scanner maintenance interruption (N=1), only 18 subjects were scanned at both pre- and post-treatment (10 = PLC, 8 = PIO). ROI analyses of FA focused on WM ROI based on several previous studies of WM integrity in cocaine dependence: (1) commissural fibers: the genu and splenium of corpus callosum (CC); (2) projection fibers: the anterior and posterior thalamic radiations; and (3) association fibers: the cingulum and the external capsule (18, 19, 22, 23, 35, 36). …”

Section: Methodsmentioning

confidence: 99%

PPAR‐gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double‐blind randomized controlled pilot trial

et al. 2017

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Background and aims Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance, and tolerability were evaluated. Design Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). Setting Single-site outpatient treatment research clinic in Houston, Texas, USA. Participants Thirty treatment-seeking adults with CUD. Mean [standard deviation (SD)] age was 47.8 (7.45), education was 12.7 (1.5), with 19.3 (7.8) years of reported cocaine use. Eighteen of the 30 participants (8=PIO; 10=PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre/post-treatment. Intervention Study medication was dispensed at thrice weekly visits along with once weekly cognitive behavioral therapy for 12 weeks. Measurements Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS), and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection), and tolerability (side effects, serious adverse events). Findings Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO. Conclusions Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.

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“…Accordingly, one might cautiously presuppose that the present results are related to chronic cocaine use plus the additional burden of alcohol abuse (although alcohol use provided no independent predictive utility), plus the influence of unmeasured factors. Such factors are likely to include variables known to alter neurobehavioral trajectories, e.g., trauma exposure, traumatic brain injury, genotypic variation, and prenatal exposure to abused substances and environmental toxicants [12,16,65-68].…”

Section: Discussionmentioning

confidence: 99%

“…Duration of cocaine use and telomere length can be considered indicators of chronicity. Previous studies have shown that severity and/or extent of cocaine use (with polysubstance use) was related to decreased WM integrity [12,71], while abstinence from cocaine was related to specific fiber tract improvements in FA value [35,72]. Associations between CUD and reductions in white matter integrity suggest allostatic shifts and possible neurotoxicity to white matter neurons [11,73,74].…”

Section: Discussionmentioning

confidence: 99%

Measures of Possible Allostatic Load in Comorbid Cocaine and Alcohol Use Disorder: Brain White Matter Integrity, Telomere Length, and Anti-Saccade Performance

Lane

Tannous

Mwangi

et al. 2018

Preprint

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34 Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, 35 resulting in changes consistent with an allostatic load model of neurocognitive impairment.36 The present study measured potential markers of allostatic load in individuals with comorbid 37 cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white 38 matter (WM) integrity, telomere length, and impulsivity/attentional bias were obtained. WM 39 integrity (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial 40 diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by T/S ratio.41 Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also 42 modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and 43 FA were associated with years of cocaine use (R 2 = 0.56 and 0.51, both p < .005) but not years 44 of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater 45 attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials 46 (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in 47 CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, 48 exploratory regression using an elastic-net model determined that more years of cocaine use, , 49 older age, larger HDDM drift rate differences and shorter telomere length were all predictive 50 of white matter integrity as measured by RD (model R 2 = 0.79). Collectively, the results 51 provide modest support linking CUD/AUD to putative markers of allostatic load. 52 Cocaine and Allostasis -3 53 54 Introduction 55Allostasis implies a shift in homeostatic systems in response to acute or chronic 56 stressors (e.g., allostatic load), described by McEwen as "the price the body pays for being 57 forced to adapt to adverse psychosocial or physical situations" [1]. Exposure to extreme or 58 pervasive stressors can result in pathophysiological change. Examination of allostatic load has 59 commonly focused on changes in the regulation of stress hormones and the sequelae of such 60 changes [2,3], but the concept can apply broadly to effects on many homeostatic systems.61 Nearly two decades ago, Koob and colleagues proposed allostatic models of chronic cocaine 62 and alcohol intake based on preclinical work [4-6], but only modest attention has focused on 63 the allostasic framework in studying human substance use disorders (SUD). Here, we focus on 64 the effects of chronic SUD in adults with co-morbid cocaine and alcohol use disorders [7][8][9]. 65Cocaine use disorder (CUD) with co-occurring abuse of other substances, e.g., 66 marijuana and alcohol use disorder (AUD), is the norm rather than the exception [10].67 Individuals who use only cocaine are of putative scientific importance with regard to isolating 68 individual drug effects. However, such investigations are more precisely understood using 69 preclinical models that can isolate dose-respon...

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White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances

Cited by 37 publications

References 45 publications

Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection

Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection

PPAR‐gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double‐blind randomized controlled pilot trial

Measures of Possible Allostatic Load in Comorbid Cocaine and Alcohol Use Disorder: Brain White Matter Integrity, Telomere Length, and Anti-Saccade Performance

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