S1-8 Imbalanced Functional Link between Large-Scale Brain Networks in Heroin Addiction

Objective:Addiction is a reward deficit and stress surfeit disorder.By using resting-state functional connectivity MRI(rs-fcMRI),the aim of this study is to investigate the pattern of aberrant brain networks in heroin addiction,and whether addiction-related brain abnormalities would be persistent or recovered after long periods of abstinence.Methods:Rs-fcMRI analysis was performed on groups of recently abstinent(no more than 3 months)heroin-dependent(HD)subjects,long-term abstinent(more than 3 years)HD subjects,and non-addicted control(CN)subjects.The left and right nucleus accumbens(NAc)were defi ned as the seed regions of interest(ROIs),a brain region implicated in relapse-related processes,including craving and reactivity to stress following acute and protracted withdrawal from heroin.For each subject,correlation maps were created by calculating Pearson’s correlation coeffi cients between the time series of the seed ROIs and that of each voxel in the brain.These correlation maps were converted to Z-value maps using Fisher’s r-to-z transformation.Two-sample t-test was performed between different groups,to identify possible addiction-related NAc functional connectivity changes.The relationship between the duration of abstinence and the altered NAc functional connectivity in the heroin group was also examined.Results:Compared to the CN group,the recently abstinent HD group showed signifi cantly increased functional connectivity between the NAc and the reward network(caudate,amygdala,thalamus and ventral medial prefrontal cortex),whereas decreased functional connectivity between the NAc and the executive control network(frontal-parietal regions).The long-term abstinent HD group also showed imbalanced functional link between the reward and executive control networks.However,with longer abstinence time,the strength of some NAc functional connectivity gradually restored to near-normal levels.Conclusion:Our results suggest that the imbalanced functional link between large-scale brain networks could serve as system-level neural underpinnings of persistent drug addiction and potential for relapse,which can at least partly be recovered after long periods of abstinence.

时间感知对海洛因成瘾者跨期决策的影响

本研究旨在探讨海洛因成瘾者的时间感知对其跨期决策的影响。研究采用时间估计任务以及跨期决策任务分别对海洛因成瘾组和对照组被试进行施测。结果发现:海洛因成瘾组出现对长时距的低估,且时间估计误差明显大于对照组;海洛因成瘾组的延迟折扣率显著高于对照组;时间感知可以显著预测海洛因成瘾者的跨期决策,而对照组无此效应。本研究从时间感知这一角度入手,在一定程度上解释了海洛因成瘾者跨期决策中的“短视”行为。

Acupuncture inhibits cue-induced heroin craving and brain activation

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point （ST36） without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

Quality of Life in Heroin Users Attending Substitution Treatment: A Multicenter Study in Italy

Quality of life (QoL) is an important measure to verify the effectiveness of therapy in substance use disorders (SUD). In this cross-sectional, multicenter study QoL has been measured in 1057 heroin dependents attending SerDs (“Servizi per le Dipendenze”, Italian National Health System Services for Addictions) and has been correlated with demographic variables and drug treatment. QoL has been measured by using GHQ-12 (12-item General Health Questionnaire), a self-administered questionnaire whose value is inversely correlated with the QoL. The median value of GHQ-12 in the study population was 12 (interquartile range [IQ] 9 - 18): 640 patients (60.6%) scored 20 points at the GHQ-12, which relates with a bad QoL. Female population showed higher GHQ12 scores when compared to male population (14 [IQ 9 - 19] vs. 12 [IQ 9 - 17], p = 0.03). Similarly, unemployed patients showed higher GHQ12 scores when compared to employed patients (15 [IQ 10 - 20] vs. 12 [IQ 8 - 16], p 20. Results show that most of patients receiving care for heroin dependence at SerDs have a positive assessment of their quality of life, and that being unemployed and having a dual diagnosis are predictors of poor QoL. Besides, data suggest that assuming buprenorphine could be a protective factor for QoL.

Characteristics of Heroin Users in Lomé(Togo)

Introduction: Opioid use is a public health problem today. The aim of this study was to describe the socio-demographic characteristics, judicial aspects, addictive behaviours and medical aspects of heroin users placed on methadone (HUM) at the Integrated Addiction Care Centre of Kodjoviakopé (CEPIAK). Framework and Method: This was a descriptive cross-sectional study conducted at the CEPIAK in Lomé, Togo, from December 1st, 2020 to January 31, 2021. Results: A total of 200 HUM were included in this study. They were Togolese in 89.0% of cases. Their mean age was 43.4 ± 9.6 years with extremes ranging from 16 to 66 years. Males accounted for 90.5% of the HUM, i.e. a sex ratio of 9.5. Primary education accounted for 39.0% of cases. Single people accounted for 44.0% of cases. One hundred and nineteen HUM (59.5%) had a history of incarceration. Cannabis, tobacco and cocaine were the other drugs associated with heroin use in 79.5%, 74.5% and 59.5% of cases respectively. A history of overdose accounted for 18.0% of the HUM in our sample. Suicide attempts accounted for 19.5% of the HUM. Tuberculosis was detected in 5.5% of the HUM. HIV accounted for 3.0% of the HUM. Conclusion: It is important for the Togolese health system to give more importance to this issue, which is shared by the medical and social sectors, in order to effectively reduce and prevent these social ills.

S4A-4 Cognitive Enhancers as A Treatment for Heroin Relapse

Rationale:Heroin addiction is a disorder that stems from maladaptive plasticity within neural circuits and produces broad cognitive deficits.Despite considerable advances in psychotherapy and pharmacotherapy for heroin addiction,but there are a few treatments for the heroin relapse after long term abstinence.Preclinical and clinical evidence indicates that the cognitive deficit during the addiction and withdrawal process,thus,cognitive enhancers may be used to treatment for heroin addiction.Objectives:The purpose of this study was to evaluate whether the cognitive enhancers would reduce the heroin relapse induced by cues which was associated with heroin reward or heroin priming in rat.Methods:Rats were trained to self-administer heroin under fixed ratio 1 schedule for two weeks and extinguished for 10 days,then the reinstatement of drug seeking induced by conditioned cues or heroin priming(250μg·kg-1,sc)was used.Results:We evaluated systemically the effects of acetylcholinase inhibitor,PDE4 inhibitor,mGlu2/3 agonist or mGlu1/5 antagonist,etc on heroin relapse.The data showed that pretreatment with acetylcholinase inhibitor,PDE4 inhibitor,mGlu2/3 agonist or mGlu1/5 antagonist could inhibit the heroin relapse induced by cues or heroin priming in a dose-dependent manner.Meanwhile,we also illustrated the circuits and signal pathway of these compounds.Conclusion:The data demonstrated that Cognitive enhancers could be used as the pharmacological treatments for heroin relapse or addiction.

柴胡防风汤治疗海洛因成瘾者顽固性偏头痛案例分析

偏头痛是以头痛剧烈、左右反复发作为特征的一种临床常见病,作为一种常见的慢性神经血管性疾病,发作时严重影响患者生活质量,而海洛因成瘾者具有个体特异性,其偏头痛病程更为顽固,而西医往往局限于症状,虽可在一定程度上缓解患者疼痛,但对于病因和个体差异缺乏探究,中医认为阿片辛香、苦、酸涩,性温,有毒,归十二经。初吸时以其辛香开泄气道,振奋精神,造成损津耗液,伐伤气血,久则成瘾,机体靠阿片提携元气,气血运行失度,导致元气耗竭,脏腑俱损。阿片成瘾为本虚标实证,毒邪雍盛为标,正气亏虚为本,脱毒后蓄积在体内的烟毒可能仍未完全排尽,而此时病情已无药力掩盖,故诸多症状顽固绵延,不易诊治。文章则是以少阳证入手运用柴胡防风汤治疗一例海洛因成瘾顽固性偏头痛患者,不仅通过“六经辨证”解释了其顽固性偏头痛病因病机,更是因人施治,根据患者辨证特点,进行加减化裁,利用附子助阳托力,兼顾吸毒患者的特殊证候,将中医学“治病求本”的宗旨体现得淋漓尽致,取得了良好的疗效,具有一定的临床参考价值。

Event-related potentials in a Go/Nogo task of abnormal response inhibition in heroin addicts

Inhibitory control dysfunction is regarded as a core feature in addicts.The major objective of this study was to explore the time course of response inhibition in chronic heroin addicts and provide the neurophysiological evidence of their inhibitory control dysfunction.The amplitudes and latencies of ERP components were studied in fourteen heroin addicts(mean duration of heroin use being(13.54±5.71) years(Mean±SD),average abstinence being((4.67±6.44) months)) and fourteen matched healthy controls with a visual Go/Nogo task.Our results showed that heroin addicts demonstrated significantly larger Go-N2 amplitudes which results in a decreased N2 Go/Nogo effect,but no statistically significant differences were found between heroin addicts and controls in P3.The ERP data suggest that fronto-central areas of heroin addicts were impaired during the inhibition process(200-300 ms) and over-activated to targets.The impaired early process might reflect an abnormal conflict monitoring process in heroin addicts.These results consolidate the inhibitory control dysfunction hypothesis in chronic heroin users.

提示潜在机会成本对男性海洛因戒断者跨期决策的改善

由于物质成瘾者的跨期决策缺陷在成瘾行为发生、发展及戒断预后中的重要作用,其已成为成瘾研究中的一个靶向干预目标。研究旨在检验提示潜在机会成本能否有效改善男性海洛因戒断者的跨期决策。两个实验分别选取男性海洛因戒断者30名与27名,让其在提示潜在机会成本和未提示潜在机会成本两种决策条件下,分别完成金钱跨期决策任务与海洛因-金钱跨类别延迟折扣任务。结果发现,提示潜在机会成本可以显著减少男性海洛因戒断者在金钱跨期决策任务中选择即时金钱奖赏的数量,但未能显著降低其在海洛因-金钱跨类别延迟折扣任务中的延迟折扣水平。研究结果表明,提示潜在机会成本可以改善男性海洛因戒断者在金钱跨期决策中的短视倾向,但无法改善其在海洛因-金钱跨类别跨期决策中的短视倾向。

海洛因通过下调DNMT3a抑制印记基因H19启动子甲基化促进雄鼠的子代成瘾与复吸的机制

目的探讨F0代雄鼠吸食海洛因对F1代大鼠成瘾与复吸的影响及机制。方法用不同剂量(1、3、9 mg·kg^(-1))海洛因处理F0代雄鼠。Western blot检测F0代雄鼠精子和F1代大鼠背侧海马组织中DNA甲基转移酶3a(DNMT3a)蛋白表达水平。DNA甲基化免疫共沉淀(MeDIP)-qRT-PCR检测H19启动子甲基化率。实时荧光定量PCR(qRT-PCR)检测H19 mRNA表达水平。构建海洛因自身给药模型,检测F1代各组大鼠的成瘾与复吸行为。结果海洛因明显降低F0代雄鼠精子中DNMT3a蛋白表达水平及H19启动子甲基化率,明显提高H19 mRNA表达水平(P<0.05)。F0代雄鼠吸食海洛因明显降低F1代大鼠背侧海马组织中H19启动子甲基化率,明显提高H19 mRNA表达水平(P<0.05)。F0代雄鼠吸食海洛因明显增加F1代大鼠在海洛因自身给药实验和复吸实验中的有效鼻触次数(P<0.05)。结论F0代雄鼠吸食海洛因会促进F1代大鼠对海洛因的成瘾与复吸,其机制可能与海洛因通过下调F0代雄鼠精子中DNMT3a表达抑制印记基因H19启动子甲基化,进而促进F1代大鼠背侧海马组织中H19 mRNA表达有关。

海洛因成瘾者免疫功能的研究

对２２例海洛因成瘾者的免疫功能的研究发现，海洛因成瘾者的ＮＫ细胞毒活性、ＩＬ－２活性、Ｔ细胞亚群的ＣＤ３和ＣＤ４细胞数量以及血清中ＩｇＡ和ＩｇＭ的含量，均比正常健康人对照组低，统计学处理后有显著性差异，表明海洛因成瘾者的免疫功能受到了抑制。

海洛因依赖者复吸相关因素的前瞻性研究

目的 :了解海洛因依赖者戒毒后的转归 ,分析复吸相关因素。方法 :随访 178名劳教的海洛因依赖者出所后 6个月的情况 ,比较复吸者和戒断者的一般人口学资料、临床特征、成瘾严重程度、伴发的精神疾病等方面的差异。结果 :随访到的 149人 (83.7% )的资料显示 ,2 2 .8%保持戒断 ,46 .3%复吸 ,2 9.5 %正在强制戒毒、劳教或自愿戒毒 ,1.3%死亡。复吸与家庭中有其他吸毒者、无强烈戒毒愿望、伴有反社会人格障碍、未参加康复治疗和入教前ASI中海洛因滥用、家庭社会关系、违法犯罪三个因子分、静脉使用毒品等有关。结论 :海洛因依赖者劳教后的复吸率较高 ,复吸与家庭生活环境、戒毒愿望、既往海洛因依赖程度、反社会人格障碍等有关 ,据此制定预防复吸治疗具有重要意义。

海洛因依赖者工作记忆、执行功能的对照研究

目的 :研究海洛因对工作记忆、执行功能的影响。方法 :对 36例海洛因依赖者和 36例正常对照进行工作记忆和执行功能测试 ,包括常识、算术、数字广度 (顺背 ,倒背 )、逻辑记忆 (即刻、延迟 )、视觉记忆 (即刻视觉再生、延迟视觉再生 )、词汇流畅、数字符号、划痕实验 (A、B)、威斯康星卡片分类实验 (WCST)。结果 :海洛因依赖组在常识、算术、数字广度 (顺背、倒背 )、视觉记忆、划痕实验 (A)测验成绩差于正常对照 ,威斯康星卡片分类实验的持续错误数大于对照而分类个数少于对照组 ,两组比较有显著的统计学差异 (P <0 0 5 )。结论 :海洛因依赖者工作记忆、执行功能存在一定程度损害 ,在康复治疗中应注意采取针对认知损害的康复治疗措施。

海洛因依赖者性心理调查分析

对71例男性海洛因依赖者调查的结果显示,海洛因依赖者性机能出现明显障碍,吸毒前平均每周性交次数5.2±1.7次,成瘾后平均0.3±0.2次(P<0.01),成瘾后性功能障碍发生率大于97%,87%性欲降低或消失;性伴侣60.6%对其性能力和表现不满意,调查结果表明,海洛因对男性发生性机能和性心理损害作用明显。

海洛因成瘾大鼠心电图及心肌超微结构改变的研究

目的探讨海洛因成瘾大鼠心电图及心肌超微结构的改变,为海洛因对心脏的损害机制提供研究基础。方法建立大鼠海洛因成瘾模型,观察心电图、HE染色及心肌超微结构改变。结果大鼠海洛因成瘾组心电图改变明显,主要表现在心率减慢、P波及T波压低、时间延长,S-T段压低、时间延长,QT间期延长,上述差异有统计学意义(P<0.05),提示心肌损伤、心肌缺血及心室功能下降。电镜改变主要表现在核浓缩,核变小,核膜皱缩,染色质凝集成块,线粒体嵴排列紊乱、消失及空泡变等,提示海洛因可造成心肌细胞超微结构的病理改变。结论海洛因对心肌可造成损害,并且心肌超微结构改变提示心肌凋亡可能是海洛因造成心肌损伤的机制之一。

海洛因依赖者心理健康状况调查

Objective:To study the mental health status of heroin addicts and their need for psychotherapy after detoxification. Methods:The mental health of 83 heroin addicts and 70 normal subjects were assessed by SCL-90, Social Support Rating Scale , EPQ, SAS and SDS. Results:As compared to normal controls, heroin additions were found to score higher on various mental health measures, including SCL-90 total and factor scores, the N score of EPQ, as well as total scores on SAS and SDS. The social support in heroin addicts scored lower than normal subjects. Conclusion:Heroin addicts have severe psychological problems, which warrant long-term psychological rehabilitation after detoxification.

海洛因成瘾大鼠心肌超微结构改变及凋亡检测

【目的】探讨海洛因成瘾大鼠心肌超微结构及心肌凋亡的改变。【方法】建立大鼠海洛因成瘾模型,采用透射电镜及脱氧核苷酸末端转移酶介导的缺口末端原位探针标记(TUNEL)观察心肌超微结构改变及心肌凋亡的情况。【结果】大鼠海洛因成瘾组电镜改变主要表现在核浓缩,核变小,核膜皱缩,染色质凝集成块,线粒体嵴排列紊乱、消失及空泡变等。TUNNEL检测结果显示海洛因成瘾大鼠心肌出现凋亡阳性细胞。【结论】上述改变说明海洛因对心肌可造成损害。

海洛因成瘾复吸大鼠脑组织超微结构和部分神经递质的变化

目的 :建立海洛因成瘾、脱毒 ,复成瘾、脱毒 ,再成瘾、脱毒 3个阶段大白鼠模型 ,了解海洛因致各阶段大白鼠脑损害的动态趋势。方法 :电镜下观察脑超微结构变化 ,荧光分光度法测定脑NA、DA、5 HT等神经递质的含量。结果 :3个阶段大鼠脑内多部位神经元胞体、轴突、树突都出现变性、凋亡、胀亡等超微病理结构改变 ,神经胶质细胞、神经毯也出现相应的超微病理结构改变 ,而且随复吸次数增多而病变加重。脑NA、DA、5 HT、含量升高 ,而且随复吸次数增多而升高。结论 :大白鼠脑组织出现广泛性超微病理结构改变 ,随复吸次数增多而病变加重 。

CE检测海洛因依赖者尿吗啡的含量

目的:采用高效毛细管电泳法(CapillaryElectrophoresis,CE)检测海洛因依赖者尿吗啡的含量。方法:BECKMAN毛细管,内径50μm,长度67cm;缓冲液:0.05mol/L磷酸氢二钠磷酸二氢钠:乙腈(80:20),pH=6.9;缓冲液温度:20℃;紫外检测波长:214nm;衡压分离,分离电压:15.00kV;自动气压进样,20pis,5sec。结果:在吗啡浓度为2～1000μg/ml范围内,线性良好,回归方程为Y=33.2928X+125.3384,r=0.999,Y为峰面积,X为浓度(μg/ml)。吗啡标准检测的日内相对标准偏差为2.58%,日间相对标准偏差为4.41%;加样回收率为90.46%,RSD为7.18%。采用此方法检测了5例海洛因依赖者脱毒前后的尿吗啡含量,脱毒前分别为34.35,46.82,60.81,25.72和44.58μg/ml,脱毒后期(末次吸毒后150h)分别减少为0.44,0.52,1.32,0.15和0.52μg/ml。结论:此方法重现性好,灵敏度高,对海洛因依赖者的尿吗啡可进行定性、定量检测,可作为海洛因依赖者诊断和脱毒疗效评价的有效手段。

海洛因成瘾者神经、内分泌及免疫系统超微病理变化研究

目的 研究海洛因成瘾者中枢神经、内分泌、免疫及生殖系统的超微结构变化。方法 应用透射电镜技术对 4例海洛因成瘾者中枢神经系统、内分泌系统、免疫系统以及生殖系统进行了观察。结果 神经系统表现为线粒体肿胀、嵴断裂、空泡变、内质网扩张、神经纤维数量减少、细胞器减少；免疫系统表现为淋巴细胞数量减少，胞浆成分减少，死亡细胞增多；内分泌系统表现为线粒体扩张，局部嵴断裂，内质网扩张；生殖系统表现为男性生精细胞减少，细胞器减少。女性未见卵泡结构。结论 海洛因滥用者的亚细胞超微结构呈急、慢性缺氧性变性、坏死改变。