Rapid Enhancement of Glutamatergic Neurotransmission in Bipolar Depression Following Treatment with Riluzole

Glutamatergic abnormalities may underlie bipolar disorder (BD). The glutamate-modulating drug riluzole may be efficacious in bipolar depression, but few in vivo studies have examined its effect on glutamatergic neurotransmission. We conducted an exploratory study of the effect of riluzole on brain glutamine/glutamate (Gln/Glu) ratios and levels of N-acetylaspartate (NAA). We administered open-label riluzole 100–200 mg daily for 6 weeks to 14 patients with bipolar depression and obtained imaging data from 8-cm³ voxels in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) at baseline, day 2, and week 6 of treatment, using two-dimensional J-resolved proton magnetic resonance spectroscopy at 4 T. Imaging data were analyzed using the spectral-fitting package, LCModel; statistical analysis used random effects mixed models. Riluzole significantly reduced Hamilton Depression Rating Scale (HAM-D) scores (d=3.4; p<0.001). Gln/Glu ratios increased significantly by day 2 of riluzole treatment (Cohen''s d=1.2; p=0.023). NAA levels increased significantly from baseline to week 6 (d=1.2; p=0.035). Reduction in HAM-D scores was positively associated with increases in NAA from baseline to week 6 in the ACC (d=1.4; p=0.053), but was negatively associated in the POC (d=9.6; p<0.001). Riluzole seems to rapidly increase Gln/Glu ratios—suggesting increased glutamate–glutamine cycling, which may subsequently enhance neuronal plasticity and reduce depressive symptoms. Further investigation of the Gln/Glu ratio as a possible early biomarker of response to glutamate-modulating therapies is warranted.     

Increased levels of adiponectin and resistin in alcohol dependence--possible link to craving

Recent studies suggested a role of appetite regulating peptides like leptin and ghrelin in alcohol dependence and particularly in the neurobiology of alcohol craving. Aim of the present study was to investigate alterations of the adipocytokines adiponectin and resistin in alcohol-dependent patients. We analyzed a sample of 88 patients at admission for alcohol detoxification and after 1 week of withdrawal treatment in comparison to 89 healthy controls. Adiponectin and resistin serum levels were measured using commercial ELISA kits. The extent of alcohol craving was obtained using the Obsessive Compulsive Drinking Scale (OCDS). Adiponectin and resistin serum levels were significantly elevated in patients with alcohol dependence at both dates (admission and after 1 week of treatment) compared to healthy controls. Adiponectin decreased significantly during the course of withdrawal (T=3.44, p=0.001) while resistin serum levels showed a slight increase (T=-1.83, p=0.071). In a multivariate approach the extent of alcohol craving was significantly associated with adiponectin but not with resistin serum levels in male patients (Beta=-0.255, p=0.025). Results for female patients were not significant. Our findings provide first evidence for an alteration of the adipocytokines adiponectin and resistin during alcohol withdrawal. Furthermore, adiponectin may be involved in the neurobiology of alcohol craving, possibly via its effects on the hypothalamic circuits.     

海洛因依赖者脱毒后稽延性戒断症状与渴求的关系

目的··:探讨海洛因依赖者脱毒后造成复吸的重要因素。方法··:采用海洛因稽延性戒断症状自评量表对封闭式戒毒病房的151例海洛因依赖者进行调查,了解稽延性戒断症状与渴求等因素的关系。结果··:稽延性戒断症状与渴求、脱毒时间及吸毒方式有密切关系,与渴求关系最密切的是稽延性戒断症状的睡眠障碍及焦虑项目。结论··:稽延性戒断症状与渴求紧密相关。     

N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study

Treatment with N-acetylcysteine (NAC) normalizes glutamate (Glu) homeostasis and prevents relapse in drug-dependent animals. However, the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated. Proton magnetic resonance spectroscopy (¹H MRS) was used to investigate Glu changes in the dorsal anterior cingulate cortex (dACC) after a single dose of NAC in cocaine-dependent patients and normal controls. In an open-label, randomized, crossover study, 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions: one group receiving no compound and the other following a single administration of 2400 mg NAC. The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity. In the medication-free condition, Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls. After administration of NAC, Glu levels were reduced in the cocaine-dependent group, whereas NAC had no effect in healthy controls. Higher baseline Glu levels were associated with higher impulsivity, and both were predictive of greater NAC-induced Glu reduction. The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients. These findings may have important implications for treatment, because abnormal Glu levels are related to relapse, and treatment with NAC prevented relapse in animal studies. Furthermore, clinical studies have indicated beneficial effects of NAC in cocaine-dependent patients, and the current study suggests that these beneficial effects might in part be mediated by the ability of NAC to normalize glutamatergic abnormalities.     

Cocaine self-administration reduces excitatory responses in the mouse nucleus accumbens shell.

Drugs of abuse affect behavior by altering neuronal communication within the brain. Previous research examining the effects of intraperitoneally administered cocaine has revealed that cocaine alters excitatory glutamatergic signaling, both directly through regulation of synaptic function, and indirectly through regulation of cellular excitability in areas of the drug reward circuitry such as the nucleus accumbens (NAcc) and ventral tegmental area. We have now extended these findings by testing the hypothesis that self-administration of cocaine might elicit similar alterations in excitatory signaling in the NAcc shell. We observed that cocaine self-administration reduces synaptically evoked excitatory responses recorded extracellularly in the NAcc shell compared to saline self-administration. This alteration was not accompanied by alterations in paired pulse ratio of synaptically evoked responses or in potentiation of these responses by application of the adenylyl cyclase activator forskolin. This reduction in glutamatergic signaling may be one mechanism by which cocaine exerts its long-term behavioral effects.     

The role of amino-acid transmitters in the pathogenesis of delirium tremens: a brief report

OBJECTIVE: The importance of serum levels of amino-acid neurotransmitters and of relevant enzymes has not been adequately evaluated in alcoholics. It is hypothesized that several of these neurotransmitters would be likely to be elevated in alcoholics overall, those with alcoholic withdrawal and, especially, individuals undergoing severe withdrawal as might be seen in delirium tremens (DTs). METHOD: The subjects for these evaluations (N = 106 men) were 46 hospitalized patients with DTs, 20 subjects with an alcohol withdrawal syndrome (AWS) in the absence of DTs, 20 alcohol-dependent individuals not demonstrating withdrawal (ADS) and 20 nonalcoholic controls. The analyses evaluated the serum levels of glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA) and glycine (Gly), as well as the activity of the relevant enzymes glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T). RESULTS: In these analyses, the subjects with DTs had significantly lower serum values for Gly and GAD, as well as for GABA, while demonstrating elevated values for Asp and Glu. CONCLUSIONS: These data support the possibility that some of the symptoms of alcohol withdrawal, especially DTs, may be related to an altered balance between neurotoxic, or excitatory, and inhibitory amino-acid neurotransmitters.     

Auricular acupuncture as an adjunct to opiate detoxification treatment: Effects on withdrawal symptoms

It was hypothesized that auricular acupuncture would lead to reduced severity of opiate withdrawal symptoms and craving when provided as an adjunct to methadone detoxification. The study used a randomized, placebo-controlled study design. The sample consisted of 83 drug misusers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for opiate dependence. Daily measures of withdrawal severity and craving were taken using the Short Opiate Withdrawal Scale and an eight-item craving questionnaire. Urine screening was used as an objective assessment of treatment adherence. The study hypothesis was not confirmed. Auricular acupuncture had no effect upon withdrawal severity or craving when provided as an adjunct to a standard methadone detoxification treatment. The results are consistent with the findings of other studies that failed to find any effect of acupuncture in the treatment of drug dependence. The failure to find any clinical gains from the adjunctive use of auricular acupuncture during detoxification from opiates raises concerns about the widespread acceptance of this intervention.     

Alcohol craving in outpatients with alcohol dependence: rate and clinical correlates

OBJECTIVE: The present study was undertaken to assess the rate and severity of alcohol craving symptoms among registered alcohol-dependent patients at a Veterans Affairs outpatient clinic. We also examined the relationship between alcohol craving and the clinical characteristics of alcohol-dependent patients. METHOD: Participants included 101 alcohol-dependent veterans enrolled in an outpatient addiction clinic. Alcohol craving was measured by the Penn Alcohol Craving Scale. Alcoholism severity and clinical characteristics were assessed with the Addiction Severity Index, Timeline Followback method, and other instruments. Three alcohol-craving groups (low, moderate, and high) were identified and compared using their demographic and clinical characteristics. Multiple regression analysis was performed to evaluate the relationship between the potential predictors and alcohol craving. RESULTS: The rate of alcohol craving was as follows: low craving (46%), moderate craving (29%), and high craving (25%). When these three craving groups were compared using univariate analyses, patients with higher alcohol craving had significantly higher alcohol composite scores (last 30 days) and severe alcohol dependence (last 1 year). In multiple regression analysis, the model explained 50% of the variance in alcohol craving, with alcoholism severity (42%), withdrawal symptoms (5%), and depression (3%) as significant predictors. CONCLUSIONS: Patients in an outpatient treatment setting had a wide range of alcohol cravings. Level of alcohol craving was directly associated with several increased indices of alcohol- and non-alcohol-related morbidity.     

Neural Correlates of Alcohol-Approach Bias in Alcohol Addiction: the Spirit is Willing but the Flesh is Weak for Spirits

Behavioral studies have shown an alcohol-approach bias in alcohol-dependent patients: the automatic tendency to faster approach than avoid alcohol compared with neutral cues, which has been associated with craving and relapse. Although this is a well-studied psychological phenomenon, little is known about the brain processes underlying automatic action tendencies in addiction. We examined 20 alcohol-dependent patients and 17 healthy controls with functional magnetic resonance imaging (fMRI), while performing an implicit approach-avoidance task. Participants pushed and pulled pictorial cues of alcohol and soft-drink beverages, according to a content-irrelevant feature of the cue (landscape/portrait). The critical fMRI contrast regarding the alcohol-approach bias was defined as (approach alcohol>avoid alcohol)>(approach soft drink>avoid soft drink). This was reversed for the avoid-alcohol contrast: (avoid alcohol>approach alcohol)>(avoid soft drink>approach soft drink). In comparison with healthy controls, alcohol-dependent patients had stronger behavioral approach tendencies for alcohol cues than for soft-drink cues. In the approach, alcohol fMRI contrast patients showed larger blood-oxygen-level-dependent responses in the nucleus accumbens and medial prefrontal cortex, regions involved in reward and motivational processing. In alcohol-dependent patients, alcohol-craving scores were positively correlated with activity in the amygdala for the approach-alcohol contrast. The dorsolateral prefrontal cortex was not activated in the avoid-alcohol contrast in patients vs controls. Our data suggest that brain regions that have a key role in reward and motivation are associated with the automatic alcohol-approach bias in alcohol-dependent patients.     

An Examination of Rostral Anterior Cingulate Cortex Function and Neurochemistry in Obsessive–Compulsive Disorder

The anterior cingulate cortex is implicated in the neurobiology of obsessive–compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy (¹H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.     

Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants’ OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.     

Perturbation of the Glutamate�CGlutamine System in Alcohol Dependence and Remission

As acute ethanol exposure inhibits N-methyl--aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu–Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy (¹H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the ¹H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the ¹H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu–Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu–Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.     

Lofexidine versus clonidine in rapid opiate detoxification

The aim of the present study is to evaluate lofexidine and clonidine, in an accelerated opiate detoxification procedure (3 days), without anaesthesia. Forty heroin-dependent individuals were detoxified, evaluating withdrawal symptoms, craving levels, mood changes, urine toxicologic screens, and dropout during therapy with either (1) clonidine, oxazepam, baclofen, and ketoprofene, with naloxone and naltrexone for 3 days (20 subjects) or (2) lofexidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone for 3 days (20 subjects).Both clonidine and lofexidine rapid detoxifications were found effective. The subjects treated with lofexidine showed significantly lower levels of withdrawal symptoms, fewer mood problems, less sedation and hypotension. No significant differences in craving levels, morphine metabolites in urine, or dropout rate were evidenced between the two groups. The early use of naltrexone during detoxification in combination with either alpha-2-agonist facilitated the acceptance for long-term naltrexone treatment. Lofexidine appeared to be more useful than clonidine in a 3-day accelerated opiate detoxification, not only to counteract withdrawal symptoms, but also in the treatment of dysphoria and mood changes. Because lofexidine does not produce hypotension, safe outpatient treatment, without hospital support, could be possible.     

Changes in Nutrition-Related Behaviors in Alcohol-Dependent Patients After Outpatient Detoxification: The Role of Chocolate

Background: Previous studies have reported changes in nutrition-related behaviors in alcohol-dependent patients after alcohol detoxification, but prospective studies assessing the effects of these changes on maintaining abstinence are lacking. Objectives: To assess changes in craving and consumption of chocolate and other sweets over time up to six months after outpatient alcohol detoxification treatment and to detect differences in abstinent versus nonabstinent patients. Methods: One hundred and fifty alcohol-dependent patients were included in this prospective observational study. Participants completed self-report questionnaires on nutrition-related behaviors and craving before detoxification treatment (baseline, t1), one week (t2), one month (t3), and six months later (t4). Results: Significant changes in craving for and consumption of chocolate as well as in craving for other sweets were observed over time. Increases were most prominent within the first month. Patients who remained abstinent until t3 consumed three times more chocolate than nonabstainers. One quarter of the patients switched from being rare (t1) to frequent (t3) chocolate eaters, and 84% of these remained abstinent until t3. No significant correlations were found between craving for alcohol and craving for or consumption of chocolate or other sweets. Conclusions/Importance: In the first month after outpatient alcohol detoxification treatment, significant changes in nutrition-related behaviors were observed. These changes were not associated with alcohol craving. For a subgroup, increasing the frequency of chocolate consumption might be a temporary protective factor with respect to alcohol relapse.     

Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence

Preclinical studies indicate that brain-derived neurotrophic factor (BDNF) is involved in neuroplastic changes underlying enduring cocaine-seeking following withdrawal. However, little is known about temporal changes in serum BDNF levels or the involvement of BDNF in craving and abstinence in early-abstinent cocaine-dependent patients. Twenty-three cocaine-dependent individuals (aged 33.65±6.85 years) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol. Serum samples were also collected for 46 healthy controls (aged 35.52±9.37 years). Demographic, consumption and clinical data were recorded for all patients. Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p=.030). Baseline BDNF levels correlated with craving (p=.034). Post-detoxification BDNF levels correlated with craving (p=.018), loss of control (p<.000), abstinence measures (p=0.031), depression (p=0.036), and anxiety (p=0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction.     

Effects of a Single Lyric Analysis Intervention on Withdrawal and Craving With Inpatients on a Detoxification Unit: A Cluster-Randomized Effectiveness Study

Background: For patients hospitalized on inpatient detoxification units, reducing negative symptoms such as withdrawal and craving is a key treatment area. Although lyric analysis is a commonly utilized music therapy intervention for clients in substance abuse rehabilitation, there is a lack of randomized controlled music therapy studies systematically investigating how lyric analysis interventions can affect patients on a detoxification unit. Objective: The purpose of this cluster-randomized effectiveness study was to measure the effects of single-session group lyric analysis interventions on withdrawal and craving with patients on a detoxification unit. A secondary purpose of this study was to determine if relationships existed between treatment effects and participants’ familiarity with the song. Methods: Participants (N = 144) were cluster-randomized to experimental (posttest only) or wait-list control (pretest only) conditions to provide treatment to all participants in an inclusive single-session design. Results: Although participants in the experimental condition had lower withdrawal and craving means than participants in the control condition, these differences were not significant. Familiarity of the song in the lyric analysis was not related to withdrawal or craving. Conclusion: Group-based lyric analysis interventions may be effective for temporarily relieving withdrawal and craving in patients on a detoxification unit. Familiarity of the song did not affect results. Implications for clinical practice, suggestions for future research, and limitations are provided.     

Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance

A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients.     

A psychobiological framework of the substrates that mediate nicotine use during adolescence

Adolescents are especially likely to initiate tobacco use and are more vulnerable to long-term nicotine dependence. A unifying hypothesis is proposed based largely on animals studies that adolescents, as compared to adults, experience enhanced short-term positive and reduced aversive effects of nicotine, as well as less negative effects during nicotine withdrawal. Thus, during adolescence the strong positive effects of nicotine are inadequately balanced by negative effects that contribute to nicotine dependence in adults. This review provides a neural framework to explain developmental differences within the mesolimbic pathway based on the established role of dopamine in addiction. This pathway originates in the ventral tegmental area (VTA) and terminates in the nucleus accumbens (NAcc) where dopamine is increased by nicotine but decreased during withdrawal. During adolescence, excitatory glutamatergic systems that facilitate dopamine are overdeveloped, whereas inhibitory GABAergic systems are underdeveloped. Thus, it is hypothesized that adolescents display enhanced nicotine reward and reduced withdrawal via enhanced excitation and reduced inhibition of VTA cell bodies that release dopamine in the NAcc. Although this framework focuses on adolescents and adults, it may also apply to the understanding of enhanced vulnerability to nicotine in adults that were previously exposed to nicotine during adolescence. The hypothesis presented in this review suggests that the clinical diagnostic criteria developed for nicotine dependence in adults, based primarily on withdrawal, may be inappropriate during adolescence when nicotine withdrawal does not appear to play a major role in nicotine use. Furthermore, treatment strategies involving nicotine replacement may be harmful for adolescents because it may cause enhanced vulnerability to nicotine dependence later in adulthood.     

音乐辅助疗法对海洛因依赖者脱毒疗效观察

目的:观察海洛因依赖患者在美沙酮替代递减治疗过程中辅以音乐疗法后的康复效果。方法:治疗组患者40例在美沙酮替代递减脱毒治疗过程中辅以音乐疗法,对照组患者40例采用单纯美沙酮替代递减脱毒治疗,观察两组病例在心理渴求、焦虑情绪变化、睡眠时间、戒断反应方面的差异。结果:治疗组病例夜间睡眠时间7天后与对照组有显著性差异(P<0.05),治疗组病例虽然心理渴求存在,但同日评分与对照组仍有显著性差异(P<0.001),治疗组辅以音乐治疗能明显改善脱毒过程中的焦虑情绪及撤药过程中(第二周)的不适,与对照组也有统计学差异(P<0.05)。结论:在美沙酮替代治疗过程中辅以音乐疗法,可以加强治疗康复效果。     

Bcl-2 rs956572 Polymorphism is Associated with Increased Anterior Cingulate Cortical Glutamate in Euthymic Bipolar I Disorder

B-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca²⁺) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells. Abnormalities in Glu function have been implicated in BD. In magnetic resonance spectroscopy (MRS) studies, anterior cingulated cortex (ACC) Glu levels have been reported to be increased in bipolar depression and mania, but no study specifically evaluated ACC Glu levels in BD-euthymia. Here, we compared ACC Glu levels in BD-euthymia compared with healthy subjects using ¹H-MRS and also evaluated the selective role of the rs956572 Bcl-2 SNP in modulating ACC Glu and Glx (sum of Glu and glutamine) in euthymic-BD. Forty euthymic subjects with BD type I and forty healthy controls aged 18–40 were evaluated. All participants were genotyped for Bcl-2 rs956572 and underwent a 3-Tesla brain magnetic resonance imaging examination including the acquisition of an in vivo PRESS single voxel (2 cm³) ¹H-MRS sequence to obtain metabolite levels from the ACC. Euthymic-BD subjects had higher Glu/Cre (creatine) and Glx/Cre compared with healthy controls. The Bcl-2 SNP AA genotype was associated with elevated ACC Glu/Cre and Glx/Cre ratio in the BD group but not in controls. The present study reports for the first time an increase in ACC Glu/Cre and Glx/Cre ratios in BD-euthymia. Also, Bcl-2 AA genotype, previously associated with lower Bcl-2 expression and increase intracellular Ca²⁺, showed to be associated with increased ACC Glu and Glx levels in euthymic-BD subjects. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD, potentially involving modulatory effects by Bcl-2 in the ACC.