Drug-induced neurotoxicity in addiction medicine

Ahmadi-Soleimani, S. Mohammad; Ekhtiari, Hamed; Cadet, Jean Lud

doi:10.1016/bs.pbr.2015.07.004

Cited by 43 publications

(20 citation statements)

References 146 publications

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“…Akt-FoxO that suppresses TLR4 signaling in Human Leukocytes is implicated in the development of T2DM [44]. There are increasing evidences that PI3K/AKT pathway are implicated in the development of T2DM [45,46].…”

Section: Shared Ttc3 Foxo Mapk and Pi3k-akt Pathways Between Ad Anmentioning

confidence: 99%

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Jiao

Wang

et al. 2020

Sci Rep

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Background: Although Alzheimer's disease (AD) is a central nervous system disease and type 2 diabetes mellitus (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach to uncovering the shared pathways between AD and T2DM involves association analysis; however, such analyses lack power to discover the mechanisms of the diseases. Methods:We develop novel statistical methods to shift the current paradigm of genetic analysis from association analysis to deep causal inference for uncovering the shared mechanisms between AD and T2DM, and develop pipelines to infer multilevel omics causal networks which lead to shifting the current paradigm of genetic analysis from genetic analysis alone to integrated causal genomic, epigenomic, transcriptional and phenotypic data analysis. To discover common causal paths from genetic variants to AD and T2DM, we also develop algorithms that can automatically search the causal paths from genetic variants to diseases and Results: The proposed methods and algorithms are applied to ROSMAP dataset with 432 individuals who simultaneously had genotype, RNA-seq, DNA methylation and some phenotypes. We construct multi-omics causal networks and identify 13 shared causal genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks. Conclusions:The results of application of the proposed pipelines for identifying causal paths to real data analysis of AD and T2DM provided strong evidence to support the link between AD and T2DM and unraveled causal mechanism to explain this link.

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Section: Shared Ttc3 Foxo Mapk and Pi3k-akt Pathways Between Ad Anmentioning

confidence: 99%

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Jiao

Wang

et al. 2020

Sci Rep

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“…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]. These arguments are not fully verifiable based on the present dataset, but provide intriguing hypotheses for systematic replications in broader samples of participants with CUD/AUD.…”

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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“…These barriers become more active during chronic drug use to partially compensate toxic effects of drugs. These natural biological barriers will decline after a period of abstinence and make the brain more vulnerable to the toxic effects of drugs during lapses (Mohammad Ahmadi Soleimani et al, 2016). However, further evidence is needed to identify the most effective strategies for harm reduction in drug-induced toxicities during drug use and relapses.…”

Section: Neurocognitive Approach To Pe: Contentmentioning

confidence: 99%

“…Hundreds and thousands of papers have described mechanisms involved in drug-induced toxicity, tolerance, withdrawal, dependency, craving, stress, allostasis, relapse, psychiatric and medical comorbidities, as well as abstinence and recovery (Courtney and Ray, 2016; Ekhtiari et al, 2016; Lemieux and Absi, 2016; Mohammad Ahmadi Soleimani et al, 2016). For example, a simple search for the terms “addiction +neuroscience/brain” yields over 14,000 results in PubMed (as of July, 2017).…”

Section: Introductionmentioning

confidence: 99%

Neuroscience-informed psychoeducation for addiction medicine: A neurocognitive perspective

Ekhtiari

Rezapour

Aupperle

et al. 2017

Progress in Brain Research

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Psychoeducation (PE) is defined as an intervention with systematic, structured, and didactic knowledge transfer for an illness and its treatment, integrating emotional and motivational aspects to enable patients to cope with the illness and to improve its treatment adherence and efficacy. PE is considered an important component of treatment in both medical and psychiatric disorders, especially for mental health disorders associated with lack of insight, such as alcohol and substance use disorders (ASUDs). New advancements in neuroscience have shed light on how various aspects of ASUDs may relate to neural processes. However, the actual impact of neuroscience in the real-life clinical practice of addiction medicine is minimal. In this chapter, we provide a perspective on how PE in addiction medicine can be informed by neuroscience in two dimensions: content (knowledge we transfer in PE) and structure (methods we use to deliver PE). The content of conventional PE targets knowledge about etiology of illness, treatment process, adverse effects of prescribed medications, coping strategies, family education, and life skill training. Adding neuroscience evidence to the content of PE could be helpful in communicating not only the impact of drug use but also the beneficial impact of various treatments (i.e., on brain function), thus enhancing motivation for compliance and further destigmatizing their symptoms. PE can also be optimized in its “structure” by implicitly and explicitly engaging different neurocognitive processes, including salience/attention, memory, and self-awareness. There are many interactions between these two dimensions, structure and content, in the delivery of neuroscience-informed psychoeducation (NIPE). We explore these interactions in the development of a cartoon-based NIPE to promote brain recovery during addiction treatment as a part of the brain awareness for addiction recovery initiative.

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Drug-induced neurotoxicity in addiction medicine

Cited by 43 publications

References 146 publications

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

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

Neuroscience-informed psychoeducation for addiction medicine: A neurocognitive perspective

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