Measures of possible allostatic load in comorbid cocaine and alcohol use disorder: Brain white matter integrity, telomere length, and anti-saccade performance

Abstract

Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, resulting in changes consistent with an allostatic load model of neurocognitive impairment.The present study measured potential markers of allostatic load in individuals with comorbid cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white matter (WM), telomere length, and impulsivity/attentional bias were obtained. WM (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by the telomere to single copy gene (T/S) ratio. Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and FA were associated with years of cocaine use (R2 = 0.56 and 0.51, both p < .005) but not years of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, exploratory regression using an elastic-net model determined that more years of cocaine use, older age, larger HDDM drift rate differences and shorter telomere length were all predictive of WM as measured by RD (model R2 = 0.79). Collectively, the results provide modest support linking CUD/AUD to putative markers of allostatic load.

White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis

“…This idea is corroborated by findings showing that altered global FA, MD, and RD were associated with numerous additionally abused substances in patients with CUD 45 . Global FA and RD values were also associated with years of CU in patients with comorbid CUD and alcohol use disorder 18 . Given that the majority of cocaine users may use and abuse additional drugs 61 , including polysubstance drugs, the inclusion of patients with CUD should allow better generalization of the current findings to real-world settings.…”

“…Based on the effect of the cocaine consumption history on the prefrontal fibers, and concerning the evidence obtained from previous studies regarding the alterations in WM integrity in the prefrontal cortex 18 , 45 , proteomic analyses were performed in the BA9 postmortem brain tissue. We used two sets of criteria to define significantly differentially expressed proteins, based on the raw and the adjusted p value, respectively.…”

“…Another meta-analysis including only data from tract-based special statistics (TBSS) studies for CUD revealed a decreased FA in the genu of the corpus callosum and a tenuous effect of pre-imaging abstinence on FA values 17 . Regarding the clinical associations, a study has found that the decrease in FA values is correlated with the years of CU 18 . Other studies have shown a positive association between the FA values at treatment onset and the abstinence duration during cocaine addiction treatment 15 , 19 .…”

Telomere and Telomerase: Biological Markers of Organic Vital Force State and Homeopathic Treatment Effectiveness

“…51,52 Studies suggest that T-cell lymphopoiesis may be discontinued in individuals with short telomeres that have been infected. 53 The same telomere shortening is observed in other health disorders, addictions or intoxications, such as obesity, 54 metabolic syndrome, 55 inflammatory and oxidative processes, 56 smoking, 57 alcoholism 58 and drug addiction, 59 or exposure to pollutants and mineral particles. 60 In addition, traumatic social exposures or psycho-emotional disorders experienced throughout life, such as chronic stress 61,62 and childhood trauma (for example, abuse, violence, racism, bullying, low socio-economic status, maternal depression, family disturbance, institutionalization) [63][64][65][66] also cause a decrease in TL.…”

The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

“…The association remained significant after adjusting for smoking, body mass index, cholesterol, perceived fitness Tannous et al, 2019 [48] Relative TL was lower in patients with alcohol disorder than in controls, but this difference was not statistically significant NR Weischer et al, 2014 [49] No association between alcohol intake and TL…”