Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence.

BACKGROUND: Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone. METHODS: Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial. RESULTS: AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking. CONCLUSIONS: Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains.

Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism.

Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term.

Neuropsychological performance deficits in adults with attention deficit/hyperactivity disorder.

Neuropsychological deficits in children diagnosed with attention deficit/hyperactivity disorder (ADHD) have been well documented utilizing various neuropsychological tests. Only recently has research begun to examine if similar deficits are present in adults with ADHD. A neuropsychological testing battery was constructed that assessed verbal learning and memory, psychomotor speed, and sustained attention--all demonstrated to be deficient in individuals with ADHD. Fifty-six self-referred nonmedicated adults with a DSM-IV diagnosis of ADHD and 38 normal comparison adults participated. ADHD adults demonstrated verbal and nonverbal memory deficits and decreased psychomotor speed compared to normal controls. Differences between ADHD and normal adults were not documented on traditional measures of executive functioning. A pattern of results emerged whereby ADHD adults' performance, particularly with regard to psychomotor speed, became more impaired as task complexity increased. This study's results largely corroborate similar neuropsychological testing results in ADHD children and recent ADHD adult findings, and support a frontal lobe dysfunction hypothesis of ADHD.

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.

The relationship of cognitive functioning to amount of recent and lifetime alcohol consumption in outpatient alcoholics.

Previous investigations of the relationship between drinking patterns and cognitive functioning have generally studied severely alcoholic patients, in whom the neurocognitive effects of alcohol consumption can be obscured by other medical or psychosocial factors. In the present study, cognitive functioning was examined after a minimum of 4 days of abstinence in 69 mildly to moderately alcohol-dependent outpatients without comorbid psychiatric, neurologic, or systemic medical illness. Circumscribed decrements in reaction time and verbal memory were associated with higher amounts of alcohol consumption in the 90 days prior to enrollment in the study, and amount of recent consumption was correlated with scores on numerous cognitive tests. In contrast, longer drinking history was not associated with poorer performance on any neuropsychological measures. Thus, in this group of high-functioning, mildly to moderately alcohol-dependent outpatients, mild cognitive deficits were related to the amount of recent, but not lifetime, alcohol consumption.

Childhood hyperactivity, gender, and Cloninger's personality dimensions in alcoholics.

Cloninger described a classification system for subtyping alcoholics based on personality dimensions of novelty seeking (NS), harm avoidance (HA), and reward dependence (RD). The relationship between these dimensions and childhood hyperactivity was examined. Mild to moderate alcohol-dependent adults (68 male and 34 female) were administered Tarter's HK/MBD Childhood Symptom Checklist, Cloninger's Tridimensional Personality Questionnaire, and the Beck Depression Inventory. Alcoholics with childhood hyperactivity (38% of sample), regardless of gender, exhibited greater NS than did alcoholics without childhood hyperactivity. Female alcoholics scored significantly higher on RD compared to males. Findings suggest that high NS, proposed by Cloninger as a predominantly male feature, is related to childhood hyperactivity, independent of gender.

Effectiveness of a continuum of care using brief and partial hospitalization for agitated dementia patients.

OBJECTIVE: A behavioral intensive care unit was originally designed as a 21-day inpatient program for treating agitation among demented patients, one of the most common behavioral disorders in this group. Due to the need to dramatically reduce length of stay and create alternative care environments, the original model was modified into an integrated continuum of care blending inpatient and outpatient care and partial hospitalization that reduced hospitalization from 21 to an average of seven days. This quasiexperimental study compared the effectiveness of the inpatient and continuum-of-care programs and conducted cost analyses. METHODS: Subjects were inpatients diagnosed with both dementia and agitation. Outcomes of 68 patients treated in the inpatient program were compared with those of 110 patients treated in the continuum of care. The primary outcome measure was patients' score on the Cohen-Mansfield Agitation Inventory, which provides a total agitation score and scores on three factors describing agitated behavior--physically aggressive behavior, verbally aggressive behavior, and nonaggressive behavior. RESULTS: A statistically significant reduction in agitation was found for patients treated in both programs, with no significant difference in outcome between programs. Patients in both programs showed significant improvements in physical aggression, verbal aggression, and nonaggressive behavior. The cost-effectiveness analysis revealed clear advantages for the continuum-of-care program, especially in the area of aggressive behaviors. CONCLUSIONS: The data suggest that the restructured program is an effective and economically feasible intervention.

Neurocognitive deficits in morbidly obese children with obstructive sleep apnea.

Neurocognitive abilities were measured in 14 morbidly obese children, five of whom had obstructive sleep apnea as determined by polysomnography. As in adults, children with obstructive sleep apnea had deficits in learning, memory, and vocabulary. Moreover, apneic/hypopneic events were inversely related to memory and learning performance among the entire sample.

Accuracy of current, 4-year, and 28-year self-reported body weight in an elderly population.

Participants in the 1987-1989 recall of the Charleston Heart Study were asked to report their current weight and to recall their weight in 1984 and 1960. Reported weights were compared with weights measured in the respective time periods. Subjects included male and female blacks and whites between ages 62 and 100 years. Correlations between reported and measured weights over all subjects were 0.979 for current, 0.935 for 4-year, and 0.822 for 28-year recall. Subjects in the lowest body mass index quartile overestimated their weight, while subjects in the highest quartile underestimated their weight. This tendency increased as the elapsed time increased. Deviations between measured and reported weights increased as performance on cognitive tests declined.

Case report of carbamazepine treatment of organic brain syndrome with psychotic features.

Impaired cognitive function in the presence of psychotic symptoms is often difficult to diagnose and treat. Carbamazepine, in a longitudinally controlled fashion, improved orientation, memory, and psychotic symptoms in a patient with previously diagnosed bipolar illness and multi-infarct dementia.

Physical attractiveness, romantic love, and equity restoration in dating relationships.

Measures of physical attractiveness, romantic love, and dominance were given to a sample of 123 dating couples. Contrary to expectation, attractive subjects were not loved more than those judged as less attractive. As suggested by equity theory, however, subjects who believed that their partners were the more attractive member of the dyad loved their partners more (p < .05) and indicated greater submission in their relationships (p < .01) than those who believed that they were the more attractive member. The results suggest that as the dating relationship progresses, the relative difference in attractiveness between partners may become a more important determinant of attraction than overall level of attractiveness.

Relationship of state-trait anxiety and type of practice to reading comprehension.

The effects of state-trait anxiety and distribution of practice on reading comprehension were studied in male and female undergraduates of average aptitude. In Experiment 1 no significant differences were found on an 8-item test between 18 high and 18 low A-trait students who studied a reading passage with a 5-sec or 2-min intertrial interval. Experiment 2 employed a total of 60 students, a state-trait measure of anxiety, a 36-item test, ego-involving instructions, and 5-sec or 2-min intertrial intervals. The following significant (p less than .05) results were found: (a) high A-trait students responded to the ego-involving instructions with greater elevations in A-state; (b) low A-trait students demonstrated superior reading comprehension; (c) a low level of A-state immediately prior to the comprehension test produced a higher test score; (d) the A-state level of high A-trait students was reduced with the 2-min intertrial interval. Collectively, the results supported a trait-state conceptualization of anxiety.