P300 in heavy social drinkers: The effect of lorazepam

The P300 component of the event-related potential (ERP) and reaction time (RT) were recorded during a simulated driving task using an oddball paradigm. ERPs and RTs were recorded from heavy social drinkers (n = 11) and low social drinkers (n = 11). A pharmacological challenge (lorazepam-ATIVAN) was administered to both groups in a double-blind procedure. In both groups, P300 amplitude was reduced and RT was increased by the presence of lorazepam; however, heavy social drinkers had longer latency P300 than low social drinkers regardless of the drug condition. The P300 amplitude results are consistent with reduced information processing being induced by lorazepam, or with reduced effectiveness of the eliciting stimuli. On the other hand, the P300 latency results suggest that P300 latency may reflect deficits in information processing induced by alcohol abuse or may have preceded the alcohol abuse. The P300 latency results are consistent with heavy social drinkers occupying an early point on the hypothesized continuum of alcohol-related brain damage.     

Treatment of alcoholism and concomitant drugs of abuse

It has been proposed that concomitant substances of abuse may have additive or synergistic properties such that alcoholics using other substances of abuse concurrently may have a harder time giving up alcohol than alcoholics abusing only alcohol. The present study surveyed 291 alcoholics in an alcohol treatment program and 86 social drinker controls matched on age, education, SES and gender. Alcohol consumption, smoking, coffee intake, other substances of abuse. Beck depression and Spielberger Anxiety (State) were measured. Alcoholics drank significantly more alcohol than did social drinkers per day (350.19 cc versus 28.08 cc, p less than 0.001), consumed more caffeine/day (486.3 mg versus 339.9 mg, p less than 0.002), smoked more cigarettes/day (27.8 versus 12.8, p less than 0.001), were more depressed (16.8 versus 4.4 (Beck), p less than 0.0001), had lower internal locus of control scores (37.6 versus 39.7, p less than 0.005), had higher scores on control by chance (22.7 versus 20.2, p less than 0.03) and were significantly more anxious (52.5 versus 33.9 on Spielberger's State Inventory p less than 0.0001). Some patients used stimulants, tranquilizers, depressants, narcotics or toluene. Only 3/258 abused alcohol without using other drugs. Results support earlier studies showing strong associations between alcohol and smoking and between alcohol and caffeine consumption. The alcoholic abusing only alcohol is very rare. Treatment programs need to pay attention to concomitant drugs of abuse.     

Electrophysiological indices predict resumption of drinking in sober alcoholics

Eighty-nine alcoholics and 54 nonalcoholic controls were tested on measures of late component event-related potentials (ERPs) using a visual “oddball” stimulus task. The alcoholics had just completed inpatient alcoholism treatment programs and were 21–45 days sober. Approximately 13 months later, subjects returned for retesting; alcoholics were classified as resumers or abstainers based on their drinking patterns during the intertest interval. Using the ERP measures from the initial testing session, alcoholics differed significantly from controls in the multivariate analysis and on P300 amplitude (P3A). Resumer alcoholics showed significantly longer N200 latencies (N2L) than abstainer alcoholics. Discriminant function analyses predicting resumer/abstainer status from N2L, P3A and N1A indicated a 63% prediction rate, x² = 5.67, p < 0.02. Addition of N2L to previously tested psychological and social predictor variables indicated an increase in the amount of variance explained. The results support a biopsychosocial model for understanding and predicting relapse in chronic alcoholics.     

Alcoholism and family history of alcoholism: effects on visual and auditory event-related potentials

In a dual-modality paradigm, visual and auditory event-related potentials were elicited in 40 alcoholic men and 30 controls, equated with the alcoholics on age and education. Half of each group had first-degree relatives who were alcoholic (family history positive). The amplitude of the visual N1 component was reduced among the alcoholics, but their auditory N1 amplitudes were normal. Average N1 amplitudes were also smaller in the family history positive subjects but this effect was significant only for auditory stimuli. Alcoholics showed reduced average P3 amplitudes to both visual and auditory signals, particularly in the family history positive group. Clearly, stratification by family history is useful for ascertainment of ERP variation among alcoholics. There were no effects on P3 latency. Among several possible explanations of P3 deficits in alcoholics, two are particularly interesting: (1) alcoholics cannot mobilize sufficient processing resources in the service of effortful cognitive functions; (2) alcoholics, being poorly motivated, apply insufficient effort to cognitive tasks. An experiment designed to test these hypotheses is described.     

P3 in young boys as a predictor of adolescent substance use

Event-related potentials were recorded during a visual, continuous performance task from 36 boys before use of alcohol or other drugs began. The boys were sons of 13 recovering alcoholics who themselves had a family history of alcoholism, 11 nonalcoholics with a family history of alcoholism, and 12 nonalcoholics with no family history of alcoholism. Four years after electrophysiological assessment, a behavioral questionnaire was administered (mean age = 16.1 years). A Substance Use score was derived from reported use of alcohol and other drugs, and from highly correlated delinquent behavior scores. P3s of lowest amplitude were associated with the highest adolescent Substance Use. The combination of reduced amplitude and prolonged latency of both target and nontarget P3 significantly predicted adolescent Substance Use scores after correction for subjects' age. Although this is the first electrophysiological predictor of adolescent substance use we are aware of, the effect was small, indicating the utility of P3 as a vulnerability marker for substance abuse disorders is likely to depend on its joint use with other measures.     

Alcohol cue-reactivity in heavy and light social drinkers as revealed by event-related potentials.

An elevated cue-reactivity evoked by alcohol-related stimuli (cues) in alcohol-dependent patients has been described for different physiological variables, including electrophysiological measures, such as event-related potentials (ERPs). Cue-reactivity has, however, also been reported for social drinkers. The aim of this study is to assess the effect of the drinking behaviours of social drinkers on cue-reactivity as measured with ERPs. Forty alcohol-related and 40 neutral pictures were presented to 15 heavy and 15 light drinkers (all males). ERPs were recorded using 21 scalp electrodes. Stimuli were presented for 500 ms with an inter-stimulus interval of 2000 ms. Heavy social drinkers displayed a cue-reactivity of significantly higher amplitude at the frontal electrode location Fz, elicited by alcohol-related, as compared to neutral, pictures. This effect was not found in light social drinkers. The results indicate that the cue-reactivity previously found in alcohol-dependent patients is also present in social drinkers, and that electrophysiological cue-reactivity is associated with alcohol consumption.     

Combined effects of methanol and ethanol on event-related potentials in non alcohol dependent men

The effects of consumption of the beverage got by distillation of Elaeis quineensis on brain functions were investigated in ten healthy, non-alcoholic men. Each subject ingested 979 mg ethanol and 21 mg methanol/kg body weight. N1, P2 and P3 components of the event-related potentials (ERP's) were recorded during a go/no go task before, 60 and 240 min. after alcohol ingestion. Subjects were presented paired auditory stimuli--standard (60%) and target stimuli in a random order and were asked to detect and signal the target unconditional stimulus by pressing a push button. In the trials 60 min. after alcohol P3 was smaller than control, both N1 and P2 were flatter 240 min. after dosing, whereas P3 amplitude was not changed then. The results are consistent with ERP's changes in chronic alcoholics and suggest that a low dose of methyl alcohol may increase ethanol effects in non alcohol-dependent man.     

Prolonged neurophysiological effects of cumulative wine drinking.

The effects of a single, large dose of alcohol have been studied extensively, but how alcohol affects the brain under more realistic social drinking situations has received scant attention. The neurophysiological effects of a cumulative dose of alcohol were investigated as subjects drank three glasses of alcoholic or placebo red wine, 1 h apart. In a double-blind procedure, electroencephalographic (EEG) activity was recorded for social drinkers during rest and performance of a working memory task at two levels of difficulty. Background EEG power in the theta, slow alpha, and beta bands increased with alcohol consumption. Along with this systemic increase in background cortical resonant activity, event-related potential (ERP) amplitudes decreased between 200 and 350 ms poststimulus and P300 latency increased, effects that occurred while relevant stimulus factors were being evaluated. These neurophysiological effects endured 3 h after drinking, whereas blood/breath alcohol concentration had decreased considerably and cognitive performance returned to normal. These findings seem to indicate that moderate social alcohol consumption has cumulative effects on brain function that persist for hours after chemical and behavioral indicators of intoxication have diminished. The results seem to indicate that neuronal populations needed for stimulus processing were less available after wine consumption (as evidenced by reduced ERP amplitudes) because of increased background oscillatory activity (as evidenced by increased background EEG power).     

THE EFFECTS OF FAMILY HISTORY, SOBRIETY LENGTH, AND DRINKING HISTORY IN YOUNGER ALCOHOLICS ON P300 AUDITORY-EVOKED POTENTIALS

Event-related potentials (ERPs) have been shown to be differentbetween alcoholics and non-alcoholics. Of particular interestto investigators has been the P300 wave. Because it has beenshown that alcohol-induced neural damage can alter P300 waves,particularly amplitude, we attempted to examine alcoholics whomost likely suffered little damage because they drank heavilyfor relatively few years (mean=6.9 years). The effects of long-termsobriety (mean=5.0 years) were also investigated to determineif cognitive functioning, as measured by auditory-evoked P300waves, varies with increased abstinence. Because family historyfor alcoholism has also been shown to influence P300 amplitudeand latency, alcoholics and controls with and without familyhistory were examined. The alcoholic group had significantlylonger latencies in P300 measures in both the family historypositive and negative groups; P300 amplitudes between alcoholicsand non-alcoholics did not vary, regardless of family history.P300 waves were unaffected by sobriety length or drinking history.The results support the hypothesis that P300 differences canbe seen between alcoholics and those at risk for alcoholism.     

Increased amplitude of P3 event-related potential in young binge drinkers

The aim of the present study was to determine how binge drinking (BD) affects brain functioning in male and female university students during the performance of a visual discrimination task. Thirty two binge drinkers and 53 controls (non binge drinkers), with no history of other drug use, personal or family history of alcoholism or psychopathological disorders, were selected. Event-related potentials (ERPs) were recorded during the performance of a visual oddball task. The latency and amplitude of the N2 and P3b components of the ERPs were analyzed. There were no differences between the groups in behavioral measures, but P3b amplitudes were significantly larger in binge drinkers than controls. This may suggest the presence of anomalies in neural processes mediating attention processing, or an imbalance (increased) of neuronal activity in P3b generators caused by the presence of BD pattern for a long time.     

A preliminary study of functional magnetic resonance imaging response during verbal encoding among adolescent binge drinkers

Binge alcohol use is common among teenagers with 28% of 12th graders reporting getting drunk in the past month. Chronic heavy drinking has been associated with verbal learning and memory deficits in adolescents and adults, yet verbal encoding in less frequently drinking teens has not yet been studied. Here, we examined functional magnetic resonance imaging (fMRI) response during verbal encoding among adolescent binge drinkers. Participants recruited from local high schools were of ages 16-18 and consisted of 12 binge drinkers and 12 demographically similar nondrinkers. Participants were all nonsmokers, and drinkers were abstinent from alcohol for an average of 33 days at the time of scanning. Participants performed a verbal paired associates learning task during fMRI acquisition. Drinkers recalled marginally fewer words than nondrinkers (P = .07). Compared with nondrinkers, bingers showed more response in right superior frontal and bilateral posterior parietal cortices but less response in occipital cortex during novel encoding (Ps < .05, clusters >1,512 μL). In addition, controls showed significant activation in the left hippocampus during novel encoding, whereas binge drinkers did not. Adolescent binge drinkers demonstrated (1) more response than nondrinkers in frontal and parietal regions, which could suggest greater engagement of working memory systems during encoding; (2) no hippocampal activation to novel word pairs; and (3) slightly poorer word pair recall, which could indicate disadvantaged processing of novel verbal information and a slower learning slope. Longitudinal studies will be needed to ascertain the degree to which emergence of binge drinking is linked temporally to these brain response patterns.     

Changes induced by short-term xylene exposure in human evoked potentials

Summary Nine healthy male volunteers were exposed to m-xylene for 3 h in the morning and 40 min in the afternoon with a 40-min break in between. The atmospheric m-xylene concentrations were either stable at 8.2 mol/l (200 ppm) or they fluctuated (5.2–16.4 mol/1; 135–400 ppm) with peaks of 16.4 mol/1 and duration of 20 min at the beginning of each exposure session. The subjects were either sedentary or exercised at 100 W for 10 min at the beginning of each session during both exposure types. The two control days, with and without exercise, were similar to the exposure days but without exposure. Evoked potentials were recorded in the morning before the exposure and immediately after the morning and afternoon sessions. Visual evoked potentials were studied to a pattern reversal stimulus (pattern VEP) and to a light flash (flash VEP). For pattern VEPs the latencies of P50, N70, P100, N135 and P170 as well as the peak-to-peak amplitude of N70 to P100 were measured. For flash VEPs the latencies of P50, N70, P100, N150 and P200 as well as the peak-to-peak amplitude of P100 to N150 were measured. Short-latency auditory evoked potentials arising in the brainstem (BAEP) were recorded for a click stimulus. The peaks 1, II, III, IV and V were identified from the grand averages. The effect of various exposure paradigms was evaluated by comparing the individual changes on an exposure day to those during the control days. The latency N135 of the pattern VEP decreased in exposure at 400 ppm with exercise, and the latency P210 in the flash VEP decreased both at the stable and fluctuating exposure with exercise. The results might suggest some activation of the arousal level of the subjects after the most intensive exposure situations.     

An epidemiologic study of effects of alcohol in the liver in hepatitis B surface antigen carriers

A total of 932 hepatitis B surface antigen (HBsAg) carriers and 1,704 HBsAg-negative inhabitants of the Yaeyama District of Okinawa, Japan, over age 20 years were investigated in 1982-1985 in order to elucidate whether an interaction between habitual alcohol intake and hepatitis B virus infection is capable of producing liver disease. All of the subjects were tested for biochemical liver functions and asked about their habitual intake of alcohol. HBsAg carriers were tested for hepatitis B e antigen (HBeAg) and antibody to HBeAg. Subjects were ranked into three categories by alcohol consumption: nondrinkers, light drinkers (1-59 g/day), and heavy drinkers (greater than or equal to 60 g/day). The prevalence of liver abnormalities in HBsAg carriers increased with alcohol consumption. The prevalence differed significantly between nondrinkers and light drinkers in HBsAg carriers (p less than 0.001), but not in HBsAg-negative inhabitants. Prevalence also differed significantly between nondrinkers and heavy drinkers irrespective of HBsAg positivity (p less than 0.001). The highest prevalence of liver abnormalities was observed in HBeAg-positive heavy drinkers (53.8%). In conclusion, this study confirms that alcohol consumption intensifies the development of liver disease caused by hepatitis B virus. Therefore, the authors see a need to educate HBsAg carriers about the risks of consuming alcohol.     

Visual evoked potentials in rotogravure printers exposed to toluene.

Visual evoked potentials (VEPs) from stimulation by checkerboard pattern reversal were examined in 54 rotogravure printers exposed to toluene (all men, aged 22-64 years, duration of exposure 1-41 years). A control group consisted of 46 subjects (23 men and 23 women; aged 22-54 years). Compared with controls the exposed group showed more frequent responses with reduced reproducibility or absence of some waves, or both; the mean P1 wave latency was prolonged and mean amplitudes N1P1 and P1N2 were reduced. The VEPs were abnormal in 24% of workers. The frequency of abnormal VEPs correlated positively with the duration of exposure to toluene and also with the degree of alcohol drinking. No association was found between measurements of VEP and electroencephalogram (EEG) or electromyogram (EMG) examinations. A VEP measurement was made in 78% of the exposed workers two years after the first examination. No statistically significant difference between the two results was found. This suggests a marked stability of the observed VEP changes. These changes can be interpreted as a subclinical sign of dysfunction of the central nervous system (CNS) related to exposure to toluene and also to alcohol consumption.     

Visual evoked potentials in rotogravure printers exposed to toluene

Visual evoked potentials (VEPs) from stimulation by checkerboard pattern reversal were examined in 54 rotogravure printers exposed to toluene (all men, aged 22-64 years, duration of exposure 1-41 years). A control group consisted of 46 subjects (23 men and 23 women; aged 22-54 years). Compared with controls the exposed group showed more frequent responses with reduced reproducibility or absence of some waves, or both; the mean P1 wave latency was prolonged and mean amplitudes N1P1 and P1N2 were reduced. The VEPs were abnormal in 24% of workers. The frequency of abnormal VEPs correlated positively with the duration of exposure to toluene and also with the degree of alcohol drinking. No association was found between measurements of VEP and electroencephalogram (EEG) or electromyogram (EMG) examinations. A VEP measurement was made in 78% of the exposed workers two years after the first examination. No statistically significant difference between the two results was found. This suggests a marked stability of the observed VEP changes. These changes can be interpreted as a subclinical sign of dysfunction of the central nervous system (CNS) related to exposure to toluene and also to alcohol consumption.     

Effects of chronic ethanol exposure on neurophysiological responses to corticotropin-releasing factor and neuropeptide Y.

Stress has been reported to influence ethanol consumption and relapse in abstinent alcoholics. The present study examined if prolonged alterations in neurophysiological responses to corticotropin-releasing factor (CRF) and neuropeptide Y (NPY), peptides known to influence stress responses, would persist during protracted ethanol abstinence. Male Wistar rats were chronically exposed to ethanol vapour (EtOH group) or air (control group) for 6 weeks. Upon removal from the vapour chambers, recording electrodes were implanted in the cortex and amygdala. The effects of intracerebroventricular infusions of CRF and NPY on electroencephalogram (EEG) and event-related potentials (ERPs) were then assessed 10-15 weeks after withdrawal from ethanol. Following abstinence from ethanol, the EtOH group displayed increased power in the 6-8 Hz frequency range and increased stability in the cortical EEG. In addition, in the EtOH group the amplitude of the P2 ERP component in the frontal cortex was decreased and the latency of the P3 ERP component in the parietal cortex was delayed, compared to the control group during baseline recording conditions. The EtOH group was also more responsive to CRF and NPY. CRF significantly increased cortical power (6-8 Hz) and increased cortical EEG stability in the EtOH group, compared to controls. Additionally, NPY significantly decreased the amplitude of the N1 ERP component in the amygdala of the EtOH group, but not in the control group. This enhanced sensitivity to CRF and NPY following chronic ethanol exposure and abstinence suggests that these peptidergic systems may play a role in the symptomatology of the prolonged abstinence syndrome.     

Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study

BACKGROUND: The effect of alcohol drinking on LDL-cholesterol concentrations is unclear. The reported variability may be due to interactions between genetic factors and alcohol intake. OBJECTIVE: The purpose of the study was to examine whether variation at the apolipoprotein E gene (APOE) locus modulates the association between alcohol drinking and LDL cholesterol. DESIGN: We used a cross-sectional design in a healthy population-based sample of 1014 men and 1133 women from the Framingham Offspring Study. RESULTS: In male nondrinkers (n = 197), LDL cholesterol was not significantly different across APOE allele groups [APOE*E2 (E2), APOE*E3 (E3), and APOE*E4 (E4)]. However, in male drinkers (n = 817), differences were observed (P: < 0.001); those with the E2 allele had the lowest concentrations. LDL cholesterol in men with the E2 allele was significantly lower in drinkers than in nondrinkers but was significantly higher in drinkers than in nondrinkers in men with the E4 allele. This APOE-alcohol interaction remained significant (P < 0.001) after age, body mass index, smoking status, and fat and energy intakes were controlled for. In women, the expected effect of APOE alleles on LDL cholesterol occurred in both drinkers (n = 791; P < 0.001) and nondrinkers (n = 342; P < 0.001). Multiple linear regression models showed a negative association (P < 0.05) between alcohol and LDL cholesterol in men with the E2 allele but a positive association in men with the E4 allele. No significant associations were observed in men or women with the E3 allele. CONCLUSION: In men, the effects of alcohol intake on LDL cholesterol are modulated in part by variability at the APOE locus.     

Drinking practices and neuropsychological test performance in sober male alcoholics and social drinkers

The relationships between alcohol intake (per occasion over time) and performance on neuropsychological tests, as they might be affected by anxiety and depression, were investigated in both an alcoholic (N = 60) and social drinking (N = 43) sample. alcoholics, a Maximum Quantity Frequency (MQF) of alcohol consumed over the previous six months was found to be the best predictor of an impairment index. Neither anxiety nor depression were correlated with test performance. In social drinkers, anxiety was the best predictor of performance on the impairment index; depression was not predictive. Neither MQF nor a commonly used measure of drinking behaviors, weighted quantity per occasion (QPO), significantly predicted performance in the social drinkers once anxiety was accounted for. The results support the assumption that in alcoholics the greater and more frequent the alcohol ingestion, the more the brain's functioning is disrupted, at least as reflected in neuropsychological test performance. Anxiety appears to play a major role in the test performance of social drinkers and should be monitored in future studies in this research area.     

TRH test in alcoholics: relationship of the endocrine results with neuroradiological and neuropsychological findings.

Neuroradiological, neuropsychological and neuroendocrine parameters were evaluated in 20 non-depressed alcoholic men after 4 weeks (N = 11) or after at least 1 year (N = 9) of abstinence from alcohol and in normal men (N = 9). With regard to normal controls, 4-week abstinent alcoholics showed larger lateral and third ventricles, without modification in the number of cerebral sulci, and altered scores of tests evaluating subcortical and frontal function. Furthermore, in these patients the TSH (thyroid stimulating hormone) and PRL (prolactin) responses to thyrotropin releasing hormone were higher than in controls, suggesting a reduced hypothalamic control of TSH and PRL secretion. Taken together, these findings suggest the presence of a frontal-subcortical disorder in alcoholics. Patients who had been abstinent from alcohol for at least 1 year were not distinguishable from controls for neuroradiological, neuropsychological and neuroendocrine findings, suggesting that the alcohol-related brain alterations are reversible after a long period of abstinence.     

Arousal-related P3a to novel auditory stimuli is abolished by a moderately low alcohol dose.

Concurrent measures of event-related potentials (ERPs) and skin conductance responses were obtained in an auditory oddball task consisting of rare target, rare non-signal unique novel and frequent standard tones. Twelve right-handed male social drinkers participated in all four cells of the balanced placebo design in which effects of beverage and instructions as to the beverage content (expectancy) were independently manipulated. The beverage contained either juice only, or vodka mixed with juice in the ratio that successfully disguised the taste of alcohol and raised average peak blood-alcohol level to 0.045% (45 mg/dl). ERPs were sensitive to adverse effects of mild inebriation, whereas behavioural measures were not affected. Alcohol ingestion reliably increased N2 amplitude and reduced the late positive complex (LPC). A large, fronto-central P3a (280 ms latency) was recorded to novel sounds in the placebo condition, but only on the trials that also evoked electrodermal-orienting responses. Both novel and target stimuli evoked a posterior P3b (340 ms), which was independent of orienting. Alcohol selectively attenuated the P3a to novel sounds on trials with autonomic arousal. This evidence confirms the previously suggested distinction between the subcomponents of the LPC: P3a may be a central index of orienting to novel, task-irrelevant but potentially significant stimuli and is an important component of the arousal system. P3b does not have a clear relationship with arousal and may embody voluntary cognitive processing of rare task-related stimuli. Overall, these results indicate that alcohol affects multiple brain systems concerned with arousal, attentional processes and cognitive-autonomic integration.