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

Abstract

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...

Assessing attentional bias and inhibitory control in cannabis use disorder using an eye-tracking paradigm with personalized stimuli.

“…The current study focused on individuals with cannabis use disorder (CUD); however, this measurement platform is likely to be relevant to other classes of abused drugs. We have previously demonstrated eye tracking measures to be highly sensitive in individuals with cocaine dependence (Dias et al, 2015;Tannous et al, 2018), as have other investigators (Marks et al, 2014;Marks, Pike, Stoops, & Rush, 2015). Eye-tracking metrics also appear sensitive in the measurement of differential attention toward cigarette cues (Domaradzka & Bielecki, 2017;Marks, Alcorn, Stoops, & Rush, 2016), alcohol cues (Christiansen et al, 2015;Jones et al, 2012;McAteer, Hanna, & Curran, 2018;Monem & Fillmore, 2017), food cues in groups with eating disorders (Ruddock, Field, Jones, & Hardman, 2018;Stojek et al, 2018), and threat detection in PTSD (Bardeen & Daniel, 2017;Lazarov et al, 2018).…”