Influence of trait behavioral inhibition and behavioral approach motivation systems on the LPP and frontal asymmetry to anger pictures

Behavioral approach and avoidance are fundamental to the experience of emotion and motivation, but the motivational system associated with anger is not well established. Some theories posit that approach motivational processes underlie anger, whereas others posit that avoidance motivational processes underlie anger. The current experiment sought to address whether traits related to behavioral approach or avoidance influence responses to anger stimuli using multiple measures: ERP, electroencephalographic (EEG) α-asymmetry and self-report. After completing the behavioral inhibition system/behavioral approach system (BIS/BAS) scales, participants viewed anger pictures and neutral pictures. BAS predicted larger late positive potentials (LPPs) to anger pictures, but not to neutral pictures. In addition, BAS predicted greater left-frontal asymmetry to anger pictures. Moreover, larger LPPs to anger pictures related to greater left-frontal EEG asymmetry during anger pictures. These results suggest that trait approach motivation relates to neurophysiological responses of anger.     

Naltrexone renders one-session exposure therapy less effective: a controlled pilot study

In vivo exposure has become the gold standard treatment for specific phobia. The endogenous opioid system is one mechanism proposed to explain why exposure provides such quick and effective treatment for specific phobia. The effect of naltrexone on fear and avoidance behavior was investigated among 15 specific phobia participants who received exposure treatment. Participants were randomly assigned to receive naltrexone, placebo, or no drug prior to attending one-session exposure treatment. Mixed effects regression results revealed that across time, the naltrexone group tolerated significantly less time in the room with the feared animal (Behavioral Avoidance Index) as compared to the placebo and no drug groups. Phobic individuals assigned to the naltrexone group had significantly higher fear ratings across time in comparison to the placebo group. Results provide support for the endogenous opioid system as a potential underlying biological mechanism associated with behavioral changes during in vivo exposure.     

A controlled trial of propoxyphene and naltrexone in patients with Tourette's syndrome.

To investigate the effect of drugs acting on the endogenous opioid system, we studied 10 adults with Tourette's syndrome who received propoxyphene hydrochloride (260 mg/day), naltrexone hydrochloride (50 mg/day), and placebo in a double-blinded, randomized clinical trial. Using a self-report scale (Tourette's Syndrome Symptom List), subjects noted a significant (p less than 0.04) lessening of tics after treatment with naltrexone when compared with placebo. An improvement in performance on the Trail Making B test, a measure of attention and visuomotor sequencing and planning, occurred after receiving naltrexone when compared with placebo (p less than 0.08) or propoxyphene (p less than 0.02). The Trail Making B test best discriminated the treatments (p less than 0.02, analysis of variance). No other treatment effects were observed for several other measures of tic severity, attentional ability, or obsessive-compulsive symptoms. Our findings indicate that pharmacological manipulation of the endogenous opioid system does influence symptoms of Tourette's syndrome.     

Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial

CONTEXT: Oral naltrexone can completely antagonize the effects produced by opioid agonists. However, poor compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence. OBJECTIVE: To evaluate the safety and efficacy of a sustained-release depot formulation of naltrexone in treating opioid dependence. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, 8-week trial conducted at 2 medical centers. PARTICIPANTS: Sixty heroin-dependent adults. INTERVENTIONS: Participants were stratified by sex and years of heroin use (> or = 5 vs < 5) and then were randomized to receive placebo or 192 or 384 mg of depot naltrexone. Doses were administered at the beginning of weeks 1 and 5. All participants received twice-weekly relapse prevention therapy, provided observed urine samples, and completed other assessments at each visit. MAIN OUTCOME MEASURES: Retention in treatment and percentage of opioid-negative urine samples. RESULTS: Retention in treatment was dose related, with 39%, 60%, and 68% of patients in the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively, remaining in treatment at the end of 2 months. Time to dropout had a significant main effect of dose, with mean time to dropout of 27, 36, and 48 days for the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively. The percentage of urine samples negative for opioids, methadone, cocaine, benzodiazepines, and amphetamine varied significantly as a function of dose. When the data were recalculated without the assumption that missing urine samples were positive, a main effect of group was not found for any drugs tested except cocaine, where the percentage of cocaine-negative urine samples was lower in the placebo group. Adverse events were minimal and generally mild. This formulation of naltrexone was well tolerated and produced a robust, dose-related increase in treatment retention. CONCLUSION: These data provide new evidence of the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence.     

Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol‐dependent and polysubstance‐dependent individuals

Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance‐dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened ‘top‐down’ control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no‐go (GNG) task, we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent polysubstance‐dependent (poly‐SUD) individuals and controls during a randomised double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly‐SUD groups respectively. Self‐reported trait impulsivity in the poly‐SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly‐SUD groups, which are predicted by trait impulsivity in the poly‐SUD group.     

EEG asymmetry: relationship to mood and risk for alcoholism in Mission Indian youth.

BACKGROUND: Left frontal electroencephalogram (EEG) alpha dominance has been hypothesized to be related to depressed mood as well as aversive motivation and emotion. However, few studies have prospectively evaluated electroencephalogram asymmetry during development in high-risk adolescents and children. METHODS: EEG alpha asymmetry was investigated in 134 Mission Indian children who were between 7 and 13 years of age. The relationships between electroencephalogram alpha asymmetry and age, gender, parental history of alcohol dependence, Native American heritage, and mood/ approach behaviors were explored. RESULTS: No significant relationship was found between frontal alpha asymmetry and age, gender, or behavioral measures of depressed mood and/or approach behaviors. However, participants with > or = 50% Native American heritage were significantly more likely to have greater electroencephalogram alpha power in the left frontal cortex than in the right. CONCLUSIONS: The present findings suggest that the hypothesized relationship between EEG alpha asymmetry and measures of depressed mood, aversive motivation, and emotion may not be universal in all age or ethnic groups. Additionally, though the relationship between greater degrees of Native American heritage and alpha asymmetry are not as yet clear, we suggest it may be more related to substance abuse than depression in this population of Mission Indians.     

Effects of dopamine and opioid receptor antagonism on the neural processing of social and nonsocial rewards

Rewards are a broad category of stimuli inducing approach behavior to aid survival. Extensive evidence from animal research has shown that wanting (the motivation to pursue a reward) and liking (the pleasure associated with its consumption) are mostly regulated by dopaminergic and opioidergic activity in dedicated brain areas. However, less is known about the neuroanatomy of dopaminergic and opioidergic regulation of reward processing in humans, especially when considering different types of rewards (i.e., social and nonsocial). To fill this gap of knowledge, we combined dopaminergic and opioidergic antagonism (via amisulpride and naltrexone administration) with functional neuroimaging to investigate the neurochemical and neuroanatomical bases of wanting and liking of matched nonsocial (food) and social (interpersonal touch) rewards, using a randomized, between-subject, placebo-controlled, double-blind design. While no drug effect was observed at the behavioral level, brain activity was modulated by the administered compounds. In particular, opioid antagonism, compared to placebo, reduced activity in the medial orbitofrontal cortex during consumption of the most valued social and nonsocial rewards. Dopamine antagonism, however, had no clear effects on brain activity in response to reward anticipation. These findings provide insights into the neurobiology of human reward processing and suggest a similar opioidergic regulation of the neural responses to social and nonsocial reward consumption.     

Opioid antagonist-induced modulation of cerebral and hippocampal development: histological and morphometric studies

The role of endogenous opioid systems in preweaning cerebral and hippocampal development was explored in rats utilizing naltrexone, a potent opioid antagonist. Sprague-Dawley rats were given daily injections (s.c.) of either 1 or 50 mg/kg naltrexone to invoke a temporary or complete blockade, respectively, of opioid receptors throughout the first 3 weeks of postnatal life; animals injected with sterile water served as controls. At weaning (Day 21), macroscopic, morphometric, and histological assessments were undertaken. In general, 50 mg/kg naltrexone had a stimulatory action on brain development, whereas 1 mg/kg naltrexone had an inhibitory influence. In most cases, both males and females were affected comparably. Opioid antagonist action was especially directed at cellular and tissue differentiation, with marked changes in macroscopic and areal dimensions and histotypic organization observed in the cerebrum. A prominent effect on the cerebrum of the 1 mg/kg naltrexone group was a substantial increase in packing density of the neural cells, reflecting a reduced area for accommodating neural elements. Changes in the hippocampus were largely restricted to the 1 mg/kg group. However, the number of granule cells was increased in the dentate gyrus of the 50 mg/kg group, suggesting that opioid receptor blockade affects cell types undergoing postnatal proliferation. Cellular elements derived prior to naltrexone treatment (e.g., pyramidal neurons) were capable of being influenced in only differentiative capacity. Our results show that endogenous opioids are natural trophic factors in brain development and provide evidence for the crucial role of endogenous opioid-opioid receptor interaction in neuro-ontogeny.     

Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain

The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment, animals were transcardially perfused and the brains were removed for verification of probe placement. Low dose naltrexone pre-treatment significantly attenuated withdrawal-induced increases of extracellular norepinephrine in the BNST, with a smaller effect in the FC. These findings suggest that alterations in norepinephrine release associated with withdrawal may be attenuated in forebrain targets of noradrenergic brainstem neurons that may underlie reduced behavioral signs of withdrawal following low dose naltrexone administration.     

Endogenous opiates and the placebo effect: a meta-analytic review

OBJECTIVE: A meta-analysis was performed to investigate the ability of placebo administration to reduce self-report of pain and to examine whether placebo-induced pain reduction might have physiological and psychological underpinnings. METHOD: Forty-five effect sizes and 1183 participants from 12 studies were meta-analyzed for the effects of placebo and the opioid antagonist, naloxone, on self-report of pain. RESULTS: Analyses showed that placebo administration was associated with a decrease in self-report of pain, and a hidden or blind injection of naloxone reversed placebo-induced analgesia. Furthermore, there were significant between-group differences for type of pain (experimental vs. postoperative/clinical) for placebo studies. CONCLUSIONS: The results support the literature illustrating that the belief and expectation of analgesia induces discrete physiological changes, leading to relief from pain, and this response may be mediated by endogenous opioids. The implications of these findings are discussed in terms of the symbolic aspect of health care and mental health providers' words and context, and their potential impact on the course of illness and well-being.     

Is alpha wave neurofeedback effective with randomized clinical trials in depression? A pilot study

Frontal asymmetric activation has been proposed to be the underlying mechanism for depression. Some case studies have reported that the enhancement of a relative right frontal alpha activity by an asymmetry neurofeedback training leads to improvement in depressive symptoms. In the present study, we examined whether a neurofeedback training designed to increase the relative activity of the right frontal alpha band would have an impact on symptoms of depressive subjects suffering from emotional, behavioral, and cognitive problems. Our results indicated that the asymmetry neurofeedback training increased the relative right frontal alpha power, and it remained effective even after the end of the total training sessions. In contrast to the training group, the placebo control group did not show a difference. The neurofeedback training had profound effects on emotion and cognition. First, we replicated earlier findings that enhancing the left frontal activity led to alleviation of depressive symptoms. Moreover, cognitive tests revealed that the asymmetry training improved performance of executive function tests, whereas the placebo treatment did not show improvement. We preliminarily concluded that the asymmetry training is important for controlling and regulating emotion, and it may facilitate the left frontal lobe function.     

Alcohol urge and plasma beta-endorphin change after alcohol challenge with naltrexone pretreatment in social drinkers

The authors have investigated the effect of naltrexone (NTX) on lowering the urge of alcohol drinking and the action mechanism of NTX. Fifteen healthy male social drinkers voluntarily participated. The experimental method was a double-blind, placebo-controlled cross-over design. To eliminate NTX effect, 1 week washout cross-over interval was taken. Subjects ingested NTX, 50 mg/day, or placebo for 1 week. Then, the alcohol (0.5 ml/kg) challenge test was done in the evening. Blood samples were taken immediately before drinking, at 20 min and at 60 min after alcohol drinking. Plasma beta-endorphin, plasma ACTH and serum cortisol levels were checked. Subjects completed self-report questionnaires such as the visual analog scales of drink urge and the alcohol sensation scales at regular intervals. In the case of NTX pretreatment, the subjects reported significantly (P=.013) less urge to drink alcohol on the self-reporting urge scales, especially at postdrinking 20 min and 60 min than placebo pretreatment. After alcohol challenge, the subjects reported significantly more dizziness (P=.015) in the case of NTX pretreatment, and reported less mood elevation trend, though not significant (P=.052). Basal plasma beta-endorphin levels were not different, but in the case of NTX pretreatment, the increasing degree of plasma beta-endorphin during 20 min after alcohol challenge was significantly (P=.039) higher than with placebo pretreatment. This results show that the NTX reduced the urge to drink alcohol with the mechanism of partially blocking the opioid positive reward system and partially mimicking the alcohol effect.     

A multimodal assessment of the relationship between emotion dysregulation and borderline personality disorder among inner-city substance users in residential treatment

The concept of emotion dysregulation has been integrated into theory and treatment for borderline personality disorder (BPD), despite limited empirical support. Expanding upon existing research on the relationship between emotion dysregulation and BPD, the present study utilized a multimodal approach to the assessment of emotion dysregulation (including two behavioral measures of the willingness to tolerate emotional distress, and a self-report measure of emotion dysregulation broadly defined) to examine the relationship between emotion dysregulation and BPD among inner-city substance users in residential treatment (n = 76, with 25 meeting criteria for BPD). Results provide laboratory-based evidence for heightened emotion dysregulation in BPD, extending extant research on BPD to underserved clinical populations. Specifically, the presence of a BPD diagnosis among a sample of inner-city inpatient substance users was associated with both higher scores on the self-report measure of emotion dysregulation and less willingness to tolerate emotional distress on the behavioral measures of emotion dysregulation. Moreover, both self-report and behavioral measures of emotion dysregulation accounted for unique variance in BPD status, suggesting the importance of utilizing comprehensive assessments of emotion dysregulation within studies of BPD. Findings suggest the need to further explore the role of emotion dysregulation in the development and maintenance of BPD among inner-city substance users in residential treatment.     

Does co‐administration of a non‐selective opiate antagonist enhance acceleration of transit by a 5‐HT4 agonist in constipation‐predominant irritable bowel syndrome? A randomized controlled trial

Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5-HT4 agonist alone. We hypothesized that the combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation-predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C-IBS. Forty-eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit.     

Endogenous opioid systems and the regulation of dendritic growth and spine formation

The role of endogenous opioid systems (endogenous opioids and opioid receptors) in neuronal development was examined in 10- and 21-day-old rats by utilizing an opioid antagonist (naltrexone) paradigm. Throughout the first 3 weeks of life, Sprague-Dawley rats were given daily subcutaneous injections of either 50 mg/kg naltrexone, a dosage that invoked a complete (24 hours/day) receptor blockade, or 1 mg/kg naltrexone, a dosage which intermittently blocked (4-6 hours/day) opioid receptors and exacerbated opioid action; animals injected with sterile water served as controls. Pyramidal cells from the frontoparietal cortex (layer III) and hippocampal field CA1, and cerebellar Purkinje cells, were impregnated by using the Golgi-Kopsch method; total and mean dendrite segment length, branch frequency, and spine concentration were analyzed morphometrically. Perturbations of endogenous opioid systems caused region-dependent alterations in dendrite complexity and/or spine concentration in all brain areas. Continuous opioid receptor blockade resulted in dramatic increases in dendrite and/or spine elaboration compared to controls at 10 days in all brain regions; however, these increases were only evident in the hippocampus at 21 days. With intermittent blockade, dendrite and/or spine growth were often subnormal, being predominant at day 21. Our results indicate that endogenous opioid systems are critical regulators of neuronal differentiation, and they control growth through an inhibitory mechanism. Considering previous findings demonstrating that neurobehavioral ontogeny is dependent on endogenous opioid-opioid receptor interactions, the present results suggest an opioid-dependent, structure-function relationship between neuronal and behavioral maturation.     

Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind,placebo-controlled study

BACKGROUND: Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms. Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy, we conducted the first published controlled study comparing and combining both compounds. METHODS: After detoxification, 160 patients with alcoholism participated in a randomized, double-blind, placebo-controlled protocol. Patients received naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. Patients were assessed weekly by interview, self-report, questionnaires, and laboratory screening. Time to first drink, time to relapse, and the cumulative abstinence time were the primary outcome measures. RESULTS: Naltrexone, acamprosate, and the combined medication were significantly more effective than placebo. Comparing the course of nonrelapse rates between naltrexone and acamprosate, the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse. The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone. CONCLUSIONS: The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism. Naltrexone and acamprosate, especially in combination, considerably enhance the potential of relapse prevention.     

Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial.

OBJECTIVE: The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence. The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic populations and with a well-defined therapy. METHOD: In this study, 131 recently abstinent alcohol-dependent outpatients were treated with 12 weekly sessions of manual-guided cognitive behavioral therapy and either 50 mg/day of naltrexone (N = 68) or placebo (N = 63) (with riboflavin added as a marker of compliance) in a double-blind, randomized clinical trial. Alcohol consumption, craving, adverse events, and urinary riboflavin levels were assessed weekly. Levels of blood markers of alcohol abuse were also ascertained during the trial. RESULTS: The study completion, therapy participation, and medication compliance rates in the trial were high, with no differences between treatment groups. Naltrexone-treated subjects drank less, took longer to relapse, and had more time between relapses. They also exhibited more resistance to and control over alcohol-related thoughts and urges, as measured by a subscale of the Obsessive Compulsive Drinking Scale. Over the study period, 62% of the naltrexone group did not relapse into heavy drinking, in comparison with 40% of the placebo group. CONCLUSIONS: Motivated individuals with moderate alcohol dependence can be treated with greater effectiveness when naltrexone is used in conjunction with weekly outpatient cognitive behavioral therapy. Naltrexone increases control over alcohol urges and improves cognitive resistance to thoughts about drinking. Thus, the therapeutic effects of cognitive behavioral therapy and naltrexone may be synergistic.     

Randomized Trial of Long-Acting Sustained-Release Naltrexone Implant vs Oral Naltrexone or Placebo for Preventing Relapse to Opioid Dependence

CONTEXT Sustained-release naltrexone implants may improve outcomes of nonagonist treatment of opioid addiction. OBJECTIVE To compare outcomes of naltrexone implants, oral naltrexone hydrochloride, and nonmedication treatment. DESIGN Six-month double-blind, double-dummy, randomized trial. SETTING Addiction treatment programs in St Petersburg, Russia. PARTICIPANTS Three hundred six opioid-addicted patients recently undergoing detoxification. INTERVENTIONS Biweekly counseling and 1 of the following 3 treatments for 24 weeks: (1) 1000-mg naltrexone implant and oral placebo (NI+OP group; 102 patients); (2) placebo implant and 50-mg oral naltrexone hydrochloride (PI+ON group; 102 patients); or (3) placebo implant and oral placebo (PI+OP group; 102 patients). MAIN OUTCOME MEASURE Percentage of patients retained in treatment without relapse. RESULTS By month 6, 54 of 102 patients in the NI+OP group (52.9%) remained in treatment without relapse compared with 16 of 102 patients in the PI+ON group (15.7%) (survival analysis, log-rank test, P?<?.001) and 11 of 102 patients in the PI+OP group (10.8%) (P?<?.001). The PI+ON vs PI+OP comparison showed a nonsignificant trend favoring the PI+ON group (P?=?.07). Counting missing test results as positive, the proportion of urine screening tests yielding negative results for opiates was 63.6% (95% CI, 60%-66%) for the NI+OP group; 42.7% (40%-45%) for the PI+ON group; and 34.1% (32%-37%) for the PI+OP group (P?<?.001, Fisher exact test, compared with the NI+OP group). Twelve wound infections occurred among 244 implantations (4.9%) in the NI+OP group, 2 among 181 (1.1%) in the PI+ON group, and 1 among 148 (0.7%) in the PI+OP group (P?=?.02). All events were in the first 2 weeks after implantation and resolved with antibiotic therapy. Four local-site reactions (redness and swelling) occurred in the second month after implantation in the NI+OP group (P?=?.12), and all resolved with antiallergy medication treatment. Other nonlocal-site adverse effects were reported in 8 of 886 visits (0.9%) in the NI+OP group, 4 of 522 visits (0.8%) in the PI+ON group, and 3 of 394 visits (0.8%) in the PI+ON group; all resolved and none were serious. No evidence of increased deaths from overdose after naltrexone treatment ended was found. CONCLUSIONS The implant is more effective than oral naltrexone or placebo. More patients in the NI+OP than in the other groups develop wound infections or local irritation, but none are serious and all resolve with treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00678418.     

Processing of Emotion Words by Patients with Autism Spectrum Disorders: Evidence from Reaction Times and EEG

This study investigated processing of emotion words in autism spectrum disorders (ASD) using reaction times and event-related potentials (ERP). Adults with (n = 21) and without (n = 20) ASD performed a lexical decision task on emotion and neutral words while their brain activity was recorded. Both groups showed faster responses to emotion words compared to neutral, suggesting intact early processing of emotion in ASD. In the ERPs, the control group showed a typical late positive component (LPC) at 400–600 ms for emotion words compared to neutral, while the ASD group showed no LPC. The between-group difference in LPC amplitude was significant, suggesting that emotion words were processed differently by individuals with ASD, although their behavioral performance was similar to that of typical individuals.     

Naltrexone depot formulations for opioid and alcohol dependence: a systematic review

Naltrexone is an opioid receptor antagonist that blocks the reinforcing effects of opioids and reduces alcohol consumption and craving. It has no abuse potential, mild and transient side effects, and thus appears an ideal pharmacotherapy for opioid dependence. Its effectiveness in alcohol dependence is less evident, but compliance with naltrexone combined with psychosocial support has been repeatedly shown to improve drinking outcomes. Limited compliance with oral naltrexone treatment is a known drawback. Several naltrexone implant and injectable depot formulations are being investigated and provide naltrexone release for at least 1 month. Studies among opioid-dependent patients indicate significant reductions in heroin use, but sample sizes are usually small. In alcohol dependence, two large multicenter trials report alcohol and craving reductions for naltrexone and placebo groups, indicating a significant but moderate effect. The pharmacokinetic profile of the injectable formulation indicates reliable naltrexone release over 1 month at therapeutic levels. Implant formulations releasing naltrexone up to 7 months are reported. Findings on safety and tolerability confirm the generally mild adverse effects described for naltrexone tablets. However, further research on therapeutic levels (i.e., opioid blocking) is warranted. The majority of naltrexone implants lacks approval for regular clinical use and larger longitudinal studies are needed. The available naltrexone depot formulations have the potential to significantly improve medication compliance in opioid and alcohol dependence. In certain circumstances, they may constitute a promising new treatment option.