Protracted impairment of impulse control under an acute dose of alcohol: A time-course analysis

Alcohol is well-known for impairing impulse control as well as its disruptive effects on other aspects of behavioral functioning, such as motor control. Time-course analyses during a single dose show rapid development of acute tolerance to impairment of motor coordination, reaction time, and levels of subjective intoxication, but no acute tolerance to impairment of the ability to inhibit responses. Evidence for a possible lag in tolerance development to the impairing effects of alcohol on inhibitory control suggests that, as drinkers' blood alcohol concentration (BAC) declines, they might exhibit prolonged impulsivity despite having an unimpaired ability to initiate action. The present study extended the time-course analysis to examine the recovery of inhibitory control under a dose of alcohol as drinkers' BAC descended from a peak of 80 mg/100 ml to a zero level. Twenty-four healthy adults were tested following 0.65 g/kg alcohol and a placebo in a counterbalanced order. They performed a cued go/no-go task that measured response inhibition. They also performed tasks that assessed reaction time, motor coordination, and completed ratings of their subjective levels of intoxication. Alcohol initially impaired inhibitory control, response time, and motor coordination and increased subjective ratings of intoxication. However, acute tolerance to the impairing effects of alcohol was observed for measures of response time, motor coordination, and ratings of intoxication and these measures returned to sober (i.e., placebo) levels by the time BAC fell to near zero. By contrast, impairment of inhibitory control showed no acute tolerance and remained impaired even when drinkers' BAC returned to near zero. Taken together, these results indicate that the disinhibiting effects of alcohol are present even when the impairing effects of alcohol on other aspects of behavior have diminished under the dose. These findings could provide a greater understanding of impulsive behaviors during the descending limb of intoxication.     

Factors Affecting the Short-Term Prognosis of Alcohol Dependent Patients Undergoing Inpatient Detoxification

Stable measures of psychological functioning require a considerable period of abstinence. However, the duration of inpatient detoxification programs has decreased dramatically in most health care systems, posing a novel challenge for clinical evaluation of patients. The present study was carried out to examine whether factors predicting short-term prognosis can be identified in alcohol dependent subjects during early stages of inpatient detoxification. Self-reports of mood states were obtained, and executive cognitive functioning was examined. Outcome was studied at 2–3 months. No correlation was found between self-reported symptoms of depression, hopelessness, and anxiety, and percentage of nondrinking days. A significant positive correlation was found between Wisconsin Card Sorting Test (WCST) performance and short-term prognosis measured by this parameter. Thus, in addition to transient withdrawal-related effects, impairments of WCST performance in early stages of alcohol detoxification may reflect more long standing deficits in problem-solving strategies, of possible relevance for matching patients to treatment services.     

Factors affecting the short‐term prognosis of alcohol dependent patients undergoing inpatient detoxification

Stable measures of psychological functioning require a considerable period of abstinence. However, the duration of inpatient detoxification programs has decreased dramatically in most health care systems, posing a novel challenge for clinical evaluation of patients. The present study was carried out to examine whether factors predicting short‐term prognosis can be identified in alcohol dependent subjects during early stages of inpatient detoxification. Self‐reports of mood states were obtained, and executive cognitive functioning was examined. Outcome was studied at 2–3 months. No correlation was found between self‐reported symptoms of depression, hopelessness, and anxiety, and percentage of nondrinking days. A significant positive correlation was found between Wisconsin Card Sorting Test (WCST) performance and short‐term prognosis measured by this parameter. Thus, in addition to transient withdrawal‐related effects, impairments of WCST performance in early stages of alcohol detoxification may reflect more long standing deficits in problem‐solving strategies, of possible relevance for matching patients to treatment services.     

Variability in behavioral impairment involved in the rising and falling BAC curve.

The purpose of this pilot study was to measure variability in behavior impairment at specific levels of the rising and falling blood alcohol concentration (BAC) curve. Behavior impairment was measured for anticipation and reaction time in addition to a variety of visual skills. Also of interest was the variability in impairment involved at specific BAC levels under single-dose and double-dose conditions. The experimental design was a variation on a 2 x 2 factorial with repeated measures on the dose of alcohol. All subjects took part in two experimental sessions, single-dose and double-dose. Sixteen (8 male and 8 female) paid subjects ages 21-40 participated in the study. Testing procedures included repeated measures on reaction time, anticipation time, perceptual vision acuity and depth perception. Breath-alcohol measures were sampled continuously at 5-minute intervals and used to plot absorption time, peak BAC and elimination time. Results showed that the average peak BAC for the double-dose was significantly higher than that of the single-dose condition. However, there were no significant differences between the single-dose and double-dose condition in either absorption time or elimination time. The performance pattern for reaction time, anticipation time and depth perception showed more impairment in the rising BAC limb than in the falling BAC limb. It is noteworthy that specific individuals exhibited different levels of impairment at a given BAC level, depending on whether the session was single- or double-dose, suggesting that one's current BAC level is less a measure of impairment than is the total quantity of alcohol consumed. A follow-up procedure to examine practice effects was conducted on eight volunteer students. Identical testing procedures, using no alcohol, produced no significant practice effects after a 3-hour period.     

Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD

Rationale

Prior research has found that adults with attention-deficit/hyperactivity disorder (ADHD) show increased sensitivity to the impairing effects of alcohol (Weafer et al., Exp Clin Psychopharmacol 17: 113–121, 2009). However, these studies have focused exclusively on the ascending limb of the blood alcohol concentration (BAC) curve, and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining.

Objective

This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb.

Methods

Adult social drinkers with ADHD and control adults completed measures of motor coordination, reaction time (RT), and subjective intoxication twice following 0.64 g/kg alcohol and placebo. The measures were administered during the ascending limb of the BAC curve and again during the descending limb.

Results

During the ascending limb, alcohol reduced motor coordination, slowed RT, and increased self-reports of subjective intoxication. Those with ADHD displayed greater impairment of motor coordination compared with controls. During the descending limb, controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT. Those with ADHD showed reduced subjective intoxication and faster RT during this time, but they did not recover motor control.

Conclusions

The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group.     

Cognitive functioning moderates the relation between Attention Deficit Hyperactivity Disorder symptoms and alcohol use in women

Previous work revealed that cognitive functioning moderated the relation between Attention Deficit Hyperactivity Disorder (ADHD) Symptoms and alcohol use [Alcohol., Clin. Exp. Res. 23 (1999) 224]. ADHD Symptoms correlated significantly with alcohol use for individuals with a poorer performance on tasks assessing prefrontal area functioning but not for individuals with higher scores on these tasks. The current study proposes to replicate this previous work and extend it in three ways. These include using a sample consisting solely of women, including the current DSM-IV [American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders (4th ed., revised). Washington, DC: Author] criteria for ADHD, and increasing the number of measures to assess cognitive functioning and drinking habits. Eighty-two female undergraduates completed four measures of alcohol use, three measures of ADHD, and six measures of cognitive functioning. Stacked two-group analyses replicated the previous moderator effect. Alcohol use and ADHD symptoms correlated .31 (ns) for the individuals who scored higher on the neuropsychological tasks. However, these constructs correlated .53 (P < .05) for individuals with lower scores on these tasks. Better performance on tasks assessing prefrontal area functioning may protect individuals from drinking in accordance with their ADHD symptoms.     

Memory encoding and retrieval on the ascending and descending limbs of the blood alcohol concentration curve

Rationale Little is known about acute effects of alcohol on memory encoding and retrieval on different limbs (ascending and descending) of the blood alcohol concentration (BAC) curve. Objectives This extensive experiment was designed to examine alcohol's effects on memory encoding and retrieval throughout a protracted drinking episode. Methods In a 9-h session, male participants consumed either alcohol (1 ml/kg) or placebo (n=32/32) over a period of 90 min and learned various materials in different memory tasks before, during, and after consuming the drinks, while their BAC levels were monitored. A week later, in a similar session, they were tested on learned materials before, during, and after drinking. Mood was assessed throughout both sessions. Results Alcohol impaired recall of words more than recognition, and cued recall most severely. Perceptual priming and picture recognition were not affected by alcohol. Alcohol impaired encoding in cued recall, recognition of completed word fragments, and free recall regardless of limb, but impaired retrieval in word recognition only during the ascending BAC. Alcohol increased negative mood on the descending limb during the first session, and on the ascending limb during the second session. Conclusions Under naturalistic drinking conditions, alcohol's effects on memory depend on task, memory process, and limb of the BAC curve. The differential effects of alcohol on retrieval during the ascending and descending limbs demonstrate the importance of examining the differential effects on the two limbs.     

Acute recovery and tolerance to low doses of alcohol: Differences in cognitive and motor skill performance

Two groups of male social drinkers were trained on a coding and pursuit rotor (PR) task, and then were tested on these two tasks under either alcohol (0.88 ml 94.6% alcohol/kg) or placebo. These treatments were repeated four times at weekly intervals, with similar blood alcohol concentrations (BAC, P>0.50) attained on all sessions (mean peak=0.082%). Drug-free coding and PR, tested prior to each drinking session, revealed no group differences or change during the course of the experiment. On initial drinking sessions, coding was disrupted (P<0.02) at rising BAC levels where PR failed to reveal impairment (P>0.50). However, immediately after peak BAC was reached, acute recovery was evident in coding at a falling BAC were PR remained impaired (P<0.01). These differences in impairment between tasks on the two limbs of the BAC curve suggested that conflicting evidence on the sensitivity of various tasks to alcohol effects may be obtained when studies examine task performance without respect to the limb of the BAC curve. Coding and PR also were differently affected by repeated exposure to alcohol. At later drinking sessions, tolerance was evident in coding, but the impairment in PR remained (P<0.01). Since the task that recovered more swiftly from a single dose of alcohol also revealed faster development of tolerance, it was suggested that the phenomena of acute recovery and tolerance may be positively correlated, and different for different types of tasks.     

Neuropsychological correlates of opioid dependence and withdrawal

Severity of opioid dependence, and performance on two successive runs of the Wisconsin Card Sorting Test (WCST), were assessed in 39 right-handed male and female methadone patients who had been randomly assigned to either a recently dosed (n=21) or 24 hr abstinent (n=18) condition. Results indicated that severity of opioid dependence was positively correlated with perseverative responses and errors on the second run of the WCST, p<.05. Further, controlling for the effect of dependence severity, patients in early methadone withdrawal made selectively more perseverative responses and errors than did recently dosed patients, p<.05, with no difference on nonperseverative errors. Findings were consistent with the hypothesis that opioid dependence, like alcoholism and cocaine addiction, is associated with disruption of executive cognitive functions mediated by the prefrontal cortex.     

The limited utility of BAC for identifying alcohol-related problems among DWI offenders.

To see if blood alcohol concentration (BAC) is a significant indicator of problem drinking or an alcohol-related diagnosis, the relationships between BAC at arrest for drinking and driving, typical drinking, alcohol-related problems, problem drinking and an alcohol abuse or dependence diagnosis were examined for 235 drinking and driving offenders referred for alcoholism evaluation. BAC and typical drinking correlated weakly and no significant relationship between alcohol-related problems and BAC was found. Further, no significant relationship was found between BAC and alcohol abuse or dependence diagnoses, or between problem drinking and BAC. These findings cast doubt on the usefulness of a single report of BAC for diagnostic and screening purposes.     

Functioning and neuronal viability of the anterior cingulate neurons following antipsychotic treatment: MR-spectroscopic imaging in chronic schizophrenia.

Magnetic resonance spectroscopic imaging provides a non-invasive approach for testing the hypothesis that neuronal function can improve under atypical antipsychotic medication leading to improvement in cognitive function. We studied two groups of schizophrenic patients, one treated exclusively with typical neuroleptics, the other with atypical medications. 1H MR-spectroscopic imaging of the anterior cingulate gyrus was performed in all patients. Perseveration errors in the Wisconsin Card Sorting Test (WCST) served as an additional marker for cingulate gyrus function. Our results showed that N-acetylaspartate (NAA), a measure of neuronal function, was closely correlated with perseveration errors seen on the WCST. Patients treated with atypical medications had fewer errors on the WCST and higher NAA levels than those on typical medications, and there was a correlation between the time treated with atypical medication, higher NAA levels and better test performance. These results suggest that atypical antipsychotics modify the function of anterior cingulate neurons in a specific manner.     

Gender differences in acute psychomotor, cognitive, and pharmacokinetic response to alcohol

This study investigated gender differences in acute response to alcohol. After practicing several cognitive and psychomotor tasks while sober, male (n = 11) and female (n = 13) social drinkers were administered a 0.65 g/kg dose of ethanol. Subjects were tested on both the ascending and descending limbs of the blood alcohol curve on measures of divided attention, short-term memory, body sway, pursuit tracking ability, and subjective level of intoxication. Blood alcohol level (BAL) was sampled frequently throughout the procedure. Females achieved consistently higher BALs than did males throughout, due mainly to higher BALs among women in the middle stage of the menstrual cycle. Women not using birth control medications also attained higher BALs than did males. When gender differences in BALs were controlled statistically, only memory functioning distinguished the groups: males recorded memory functioning more quickly on the descending limb of the blood alcohol curve than did females. Stage of menstrual cycle or use of birth control medications did not influence psychomotor or cognitive performance while women were intoxicated.     

Prefrontal grey-matter changes in short-term and long-term abstinent methamphetamine abusers

Authors explored grey-matter density in 29 methamphetamine abusers and 20 healthy comparison subjects using voxel-based morphometry. Grey-matter density changes and performances on the Wisconsin Card Sorting test (WCST) were also compared between 11 short-term (<6 months) and 18 long-term (>or=6 months) abstinent methamphetamine abusers. Methamphetamine abusers had lower grey-matter density in the right middle frontal cortex (corrected p<0.05) and more total errors in the WCST (p<0.01) relative to healthy comparison subjects. Grey-matter density decrease in the right middle frontal cortex correlated with total errors in the WCST in methamphetamine abusers (r=-0.45). Long-term abstinent abusers had significantly less right middle frontal grey-matter density decrease (p<0.01) and total errors in the WCST (p<0.01) than short-term abstinent abusers, but more than the healthy comparison subjects. We report that methamphetamine abusers have prefrontal grey-matter deficit, which may, in part, recover with long-term abstinence.     

Impaired performance in a test of decision-making by opiate-dependent tobacco smokers

This study tested whether opiate dependence, tobacco smoking, or their combination accompanied impaired performance on the gambling task (GT), which tests decision-making. GT previously detected impairments in patients with lesions of the ventromedial prefrontal cortex and in substance abusers. Four groups were matched on demographic characteristics and intelligence: methadone-maintained smokers (n = 9) and nonsmokers (n = 9), and control (i.e., not opiate-dependent) smokers (n = 9) and nonsmokers (n = 10). The Wisconsin Card Sorting Task (WCST) was administered to test whether differences in GT performance reflected generalized deficits in prefrontal cortical function. While there were no significant group differences on the WCST, groups differed significantly on GT performance (F(3,31) = 2.95, P = 0.048), controlling for depressive symptom ratings and childhood attention deficit hyperactivity disorder. Methadone-maintained smokers (but not nonsmokers) performed more poorly than either of the two control groups (P = 0.007 versus smokers; P = 0.024 versus nonsmokers). In a planned analysis of methadone-maintained subjects, smokers scored more poorly on GT than nonsmokers (F(1,18) = 5.64, P = 0.032) and had more treatment failures (67% heroin use during the last 30 days versus 20%). The findings suggest that among opiate-dependent individuals, tobacco smoking may be a marker for a more severe form of substance abuse disorder, reflecting impaired decision-making, as modeled by GT.     

Relationship between the cardiac response to acute intoxication and alcohol-induced subjective effects throughout the blood alcohol concentration curve

RATIONALE: There is evidence to suggest that individual differences in the subjective response to alcohol exist and exaggerated cardiac response to alcohol has been suggested to be a marker of increased sensitivity to the stimulant properties of alcohol. OBJECTIVES: The present investigation examines the relationship between cardiac reactivity to alcohol measured on the ascending limb of the Blood Alcohol Concentration (BAC) curve and the subjective stimulant and sedative effects of alcohol throughout the BAC curve. METHODS: The stimulant and sedative effects of alcohol anticipatory to alcohol and during the ascending and descending limbs of the BAC curve were evaluated using the Biphasic Alcohol Effects Scale in 39 male social drinkers. RESULTS: Cardiac response to ethanol measured on the ascending limb of the BAC curve was positively correlated with intoxicated stimulant effects at numerous time points during the ascending and descending limbs of the BAC curve (ps < 0.01). No associations were found between cardiac change following alcohol and alcohol-related sedative effects at any time point. CONCLUSIONS: Objective and subjective reports of stimulation post-alcohol ingestion may increase risk for problematic drinking.     

Cognitive performance measured on the ascending and descending limb of the blood alcohol curve

40 medical students were randomly assigned to an alcohol (1.32 ml per kilogram) or placebo group and were tested on two cognitive tests and a personality inventory. 10 alcohol subjects were tested on the Shipley-Hartford and Maudsley Personality Inventory on the ascending limb and 10 subjects were tested on the descending limb of the blood alcohol curve at a blood alcohol level of 0.08%. All 20 alcohol subjects were also tested on the Raven's Progressive Matrices on the descending limb. Placebo subjects were tested at comparable times as alcohol subjects. Performance was poorer on the Shipley for subjects tested on the ascending limb than for subjects tested at comparable blood alcohol levels on the descending limb. It was also found that more errors of omission were made on the Shipley in the ascending group than in the descending group. The nature of the alcohol impairment observed on the ascending limb seemed to be related to an expressive type deficit. Effects of alcohol on personality variables as measured by the Maudsley could not account for these differences. Subjects tested on the descending limb did not perform significantly differently from placebo subjects on either the Shipley or Matrices. Fast drinkers were found to have a slower elimination rate than slow drinkers, and elimination rate was positively related to cognitive performance. Methodological implications for future alcohol research are discussed.This research was supported in part by Public Health Service grant 14702 from the National Institute of Mental Health subproject neuropsychological concomitants of alcohol under the direction of Arthur Vega and Oscar A. Parsons.     

Induction of alkoxyresorufin O-dealkylases and UDP-glucuronosyl transferase by phenobarbital and 3-methylcholanthrene in primary cultures of porcine ciliary epithelial cells

Our previous studies have shown that drug-metabolizing activities in the eye are highest in the ciliary body, a tissue responsible for aqueous humor production. In this work, we have separated nonpigmented epithelial (NPE) cells and pigmented epithelial (PE) cells from porcine ciliary body and determined basal and induced activities of 7-ethoxyresorufin (ER) O-dealkylase, 7-pentoxyresorufin (PR) O-dealkylase, and UDP-glucuronosyl transferase (UDP-GT) using primary cultures of separated cells. ER and PR activities were associated primarily with NPE cells and were very low in PE cells. Treatment of NPE cells with phenobarbital (PB) for 48 hr resulted in about a 4-fold increase in PR O-dealkylase activity but only a 1.3-fold rise in ER O-dealkylase activity. Conversely, 3-methylcholanthrene (MC) treatment augmented the ER O-dealkylase activity of NPE cells 6 times over the basal activity in 48 hr but had little effect on PR O-dealkylase activity. Both NPE and PE cells had low basal UDP-GT activities. UDP-GT activity increased about 5-fold in PB-treated PE cells and about 4-fold in PB-treated NPE cells in 48 hr. The results of MC treatment were similar to those of PB treatment; enhancement of UDP-GT was more pronounced in PE cells than in NPE cells. Induction by PB and MC of ER O-dealkylase, PR O-dealkylase and UDP-GT activities in ciliary NPE and PE cells was inhibited almost completely by 3.5 microM cyclohexamide and 40 nM actinomycin D. The heterogeneous distribution of these enzymes suggests that a harmonious interplay between NPE and PE cells is important for metabolic detoxification of blood plasma prior to aqueous humor formation.     

Relationship between effects of alcohol on psychomotor performances and blood alcohol concentrations

Ethanol is a social drug and has been generally known to be a CNS depressant. A large fluctuation of blood alcohol concentration (BAC) is well-known to occur due to main factors such as the genetic polymorphism of the main alcohol metabolizing enzymes and the effect of blood. Few studies have substantially discussed the relationship between impaired CNS activities and BAC. In this study, focusing on the correlation of BAC, we investigated the acute effects of alcohol intake on cognitive performance in humans by objective evaluation methods consisting of the attention-demanding cognitive tasks. Tasks were administered to ten healthy male volunteers before and after ingesting established amounts of alcohol. With increased BAC, we observed prolongation of reaction time performances and lowering of a coordination performance. From the results, we concluded that cognitive performance deteriorates with an increase of BAC. Additionally, the BAC threshold that causes significant impairment of cognitive performance was estimated to be approximately 50 mg/dl (ca. 10 mM).     

Trait impulsivity and cognitive domains involving impulsivity and compulsivity as predictors of gambling disorder treatment response

Background and aimsGambling disorder (GD) is a highly heterogeneous condition with high rates of chronicity, relapses and treatment dropout. The aim of this study was to longitudinally explore the associations between trait impulsivity, impulsivity-compulsivity related cognitive domains, and treatment outcome in an outpatient sample of adult patients with GD.Methods144 adult male participants diagnosed with GD undergoing cognitive-behavioural treatment (CBT) at a specialized outpatient service completed a series of neuropsychological tests to assess executive functioning (including cognitive flexibility, inhibition control and decision making) and psychometric questionnaires.ResultsTrait impulsivity predicted low compliance [UPPS-P negative urgency (B = 0.113; p = 0.019)] and relapse [UPPS-P negative urgency (B = 0.140; p = 0.015)] at 5 weeks of treatment and dropout at the end of treatment [(UPPS-P sensation seeking B = 0.056; p = 0.045)]. Cognitive flexibility performance predicted: dropout rates at the end of treatment [WCST perseverative errors (B = 0.043; p = 0.042)]; dropout [WCST categories completed (B = −1.827; p = 0.020)] and low compliance or relapses at follow-up [WCST perseverative errors (B = 0.128; p = 0.020)]; and time to first relapse [WCST failure to maintain set (B = −0.374; p = 0.048)] and time to dropout [WCST perseverative errors (B = 0.0198; p = 0.019)].ConclusionsOur findings indicate impulsivity-compulsivity levels may influence response to GD treatment (i.e.: low compliance and dropout or relapse rates) thus representing a potential target for improving treatment outcomes.     

Biphasic stimulant and sedative effects of ethanol: are children of alcoholics really different?

Children of alcoholics (COAs) have an increased risk of developing alcoholism themselves. The mechanisms responsible are not yet known. One compelling theory postulates that COAs may have an increased sensitivity to the stimulant effects of alcohol during the ascending limb of the blood alcohol curve combined with a decreased sensitivity to the putatively undesirable sedative effects of the drug during the descending limb, providing a particularly strong motivation to drink. Consistent with this theory, we hypothesized that compared to children of nonalcoholics (CONAs), COAs would display higher levels of ascending limb stimulation and lower levels of descending limb sedation. In the present study, 100 college students, who were either COAs (n=18) or CONAs (n=82), completed the Biphasic Alcohol Effects Scale (a self-report measure of stimulation and sedation): (1) before consuming 0.85n ml/kg ethanol; (2) during the ascending limb of their BAC, and; (3) during the descending limb of their BAC. Although findings indicated that COAs and CONAs had comparable levels of sedation at each time point, a significant GroupxTime interaction (P<.02) indicated that COAs had greater increases in stimulation from baseline than CONAs, providing partial support for our hypothesis. Interestingly, simple effects analyses revealed that COAs had lower baseline levels of stimulation but almost identical levels of ascending and descending limb stimulation as CONAs, suggesting that increased sensitivity to alcohol among COAs may be the result of baseline understimulation. Overall, findings suggest that theorized differences between COAs and CONAs may be due in part to broader trait differences or other nonpharmacological factors.