Methylation and expression quantitative trait locus rs6296 in the HTR1B gene is associated with susceptibility to opioid use disorder

Li, Yunxiao; Lu, Yujiao; Xie, Qiaoli; Zeng, Xiaofeng; Zhang, Rui; Dang, Wei; Zhu, Yan; Zhang, Jianbo

doi:10.1007/s00213-022-06141-5

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…Much less is known regarding MOR signaling in the cortex with repeated opioid exposure 50 . Serotonergic neurotransmission is implicated in motivated behaviors in addictive substancerelated reward processing 51 , 5-HT neurons respond to aversive stimuli, and variants of 5-HT 1b receptor, including expression in the frontal cortex, are associated with susceptibility to heroin use disorder [52][53][54] . The remarkable specificity between activity changes and receptor-type expression levels observed here suggests the utility of different classes of chemicals to control particular parts of the circuitry, for example, serotoninergic antidepressants may aid in opioid tapering.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychology of chronic back pain managed with long-term opioid use

Baliki,

Vigotsky,

Rached

et al. 2024

Preprint

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Chronic pain is commonly treated with long-term opioids, but the neuropsychological outcomes associated with stable long-duration opioid use remain unclear. Here, we contrasted the psychological profiles, brain activity, and brain structure of 70 chronic back pain patients on opioids (CBP+O, average opioid exposure 6.2 years) with 70 patients managing their pain without opioids. CBP+O exhibited moderately worse psychological profiles and small differences in brain morphology. However, CBP+O had starkly different spontaneous brain activity, dominated by increased mesocorticolimbic and decreased dorsolateral-prefrontal activity, even after controlling for pain intensity and duration. These differences strongly reflected cortical opioid and serotonin receptor densities and mapped to two antagonistic resting-state circuits. The circuits’ dynamics were explained by mesocorticolimbic activity and reflected negative affect. We reassessed a sub-group of CBP+O after they briefly abstained from taking opioids. Network dynamics, but not spontaneous activity, reflected exacerbated signs of withdrawal. Our results have implications for the management and tapering of opioids in chronic pain.

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Section: Discussionmentioning

confidence: 99%

Neuropsychology of chronic back pain managed with long-term opioid use

Baliki,

Vigotsky,

Rached

et al. 2024

Preprint

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Section: Is It Possible To Protect Against/reverse the Metabolic And ...mentioning

confidence: 99%

“…Similarly, in the heroin abuse disorder methylation levels of CpG sites HTR1B_07 and HTR1B_26 and the promoter region of the HTR1B gene were hypermethylated in heroin abusers compared to healthy controls (14). The enzymes involved in epigenetic modifications of the DNA as well as the histone methylation/acetylation are reliant on specific micronutrient cofactors (Figure 3) and their activity can be directly impacted by the levels of these cofactors like nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD) as well as metabolic compounds like L-carnitine, Q10, etc.…”

mentioning

confidence: 92%

Drug abuse results in metabolic and epigenetic changes in body which may contribute to disease risk: Role of L-carnitine and nutrients

Virmani¹

2023

Adv. Drug Alcohol Res.

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Introduction-Drug abuse and health riskDrug abuse is associated with significant health risk (1, 2). Studies are also showing that there is an important connection between circadian rhythms, metabolism and addiction (3)(4)(5). Study analyzing the liver metabolome of mice deficient in the expression of the dopamine D2 receptor (D2R) in striatal medium spiny neurons, found profound changes in the liver circadian metabolome compared to control mice (3). Further drugs that increase dopamine levels like cocaine disrupt circadian metabolic profiles in the liver. It is becoming evident that a strict communication exists between the CNS, and metabolism and this equilibrium can be altered by drug abuse (Figure 1). This loss of equilibrium in drug abusers may increase risk of metabolic dysfunctions which may result in worsening addiction and possible disease states such as those manifested as the metabolic syndrome. Drug abuse effects on metabolism and epigeneticsThe metabolic syndrome is a collection of metabolic abnormalities, including hyperinsulinemia, hypertension, dyslipidaemia, and abdominal obesity, and may be triggered by initial discrepancies at the cellular level in critical metabolic pathways. These primary, small metabolic pathway disparities probably cascade with time leading in time to significant health problems. Some indications that drug abuse may increase the risk of the metabolic syndrome include the observation that drug-abusing patients have higher rates of diabetes complications. How drug abuse increases the risk to disease is being shown to be linked to changes in metabolism and epigenetics that are associated with the increased disease susceptibility. To counter these drug abuse related deleterious effects various studies, suggest that certain metabolic and antioxidant compounds like L-carnitine, thiamine (B1), co-enzyme Q10 etc., may be useful (6).Drugs of abuse can be roughly categorised in different groups depending in part on their CNS activities, such as stimulants, amphetamines, hallucinogens, narcotics, inhalants, anaesthetics, anabolic steroids, and antipsychotics/antidepressants etc., (6). Each category

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