Neurophysiological correlates of response production and inhibition in alcoholics

Scalp recordings of the P300 component of the event-related potential were made from a group of medication-free, chronic male alcoholics and a control group, participating in a visual Go/No Go reaction time paradigm. Subjects were presented with large and small forms of the letters T and V. The large forms (Go stimuli) required a button press with either the left or right hand, whereas the small forms (NO Go stimuli) required response inhibition. Recordings were made from 31 electrodes that, for statistical analyses, were grouped into five regions: frontal, central, parietal, occipital, and temporal. The results indicated that, in each of the five regions, both Go and NO Go response amplitudes were larger in the controls than in the alcoholics. No group differences in latency were observed in any region. Surface energy (Wang et al., Brain Topogr. 6:193-202, 1994) magnitudes paralleled P300 amplitudes and in the controls, compared with the alcoholics, were larger during both Go and No Go trials. Our findings suggest that abstinent, chronic alcoholics differ electro-physiologically from control individuals. These differences are manifested as widespread reductions in P300 amplitudes during the performance of a simple information processing paradigm. The reduced amplitudes may reflect a deficiency in an inhibitory mechanism proposed to underlie P300 generation.     

Brain atrophy and cognitive function in older abstinent alcoholic men

We used computer-aided magnetic resonance image analysis and an age-normed battery of neuropsychological tests to measure brain atrophy and cognitive function in 14 older abstinent alcoholic men and 11 older controls in the expectation that these subject groups would show the greatest and most persistent cerebral effects consequent to chronic alcoholism. The abstinent alcoholics exhibited cognitive impairments (primarily in memory and visual-spatial-motor skills) compared with the controls. In contrast, we found no difference in global cerebral atrophy between the groups, although two alcoholics had extensive atrophy compared with all other subjects. However, there was a stronger association between age and ventricular dilation in the alcoholic sample compared with controls. We conclude that a substrate other than magnetic resonance imaging-detectable global atrophy must underlie the persistent cognitive impairments evident in the sampled alcoholics. Furthermore, if there are global atrophic changes in the brain associated with chronic alcoholism, these effects are not ubiquitous and/or may be reversible in most patients with sufficient abstinence.     

Normal cholesterol measurements in white collar workers still at cardiovascular risk?

This study investigated underlying mechanisms of the verbal memory disorder associated with chronic alcoholism. Previous investigations have suggested that alcoholics are more vulnerable to interference effects on verbal learning and memory tasks, both with respect to retroactive interference (RI) and proactive interference (PI); this was the hypothesis of the current study. Measures of RI and build-up and release from PI were administered to 31 abstinent male chronic alcoholics and 24 healthy male nonalcoholic control subjects. Alcoholics demonstrated more sensitivity to RI than controls. Additionally, alcoholics displayed a more rapid build-up of PI, although they showed normal release. An increased interference effect was found to be a component of chronic alcoholics' verbal memory impairment and may differentiate chronic alcoholism from other disorders affecting verbal learning and memory.     

The thyrotropin releasing hormone stimulation test in alcoholism

The mechanism for a blunted thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in alcoholics is not known. We performed a combined TRH and gonadoliberin stimulation test on three well-defined groups of nondepressed alcoholic men. Group A comprised patients with acute withdrawal symptoms (n = 28), group B patients abstinent for 5-8 weeks (n = 29) and group C patients who had been abstinent for > 2 years (n = 16). Twenty-two healthy male volunteers were used for comparison. A blunted TSH response to TRH (delta TSH < 5 microU/l) occurred only in groups A (39%) and B (17%). In group A delta TSH showed a significant negative correlation with the severity of withdrawal symptoms and a significant positive correlation with serum magnesium levels. In group B, patients with a family history of alcoholism had significantly lower delta TSH levels than those without such a family history. Groups did not differ with respect to basal and delta prolactin, and TSH responses were not significantly associated with vitamin deficiency, cortisol levels or free thyroid hormone levels. We conclude that TRH stimulation test blunting appears to be related to factors operating in the withdrawal state and improves with continued abstinence. A possible role of genetic factors and serum magnesium needs to be further explored.     

Amygdala core nuclei volumes are decreased in recurrent major depression

Chronic myopathy is a common complication of alcoholism, but its natural history has not been well described. We, therefore, studied muscle structure and function in a 5-year study of 30 chronic alcoholics who became abstinent and 20 who relapsed, and 40 control subjects. The mean strength of the abstaining alcoholics increased from 18.6 to 23.2 kg; but, after 5 years, they were still substantially weaker than controls. In a subset who showed histological myopathy, the strength of half of the patients remained two standard deviations below that of controls. Alcoholics who relapsed tended to become progressively weaker (21.7 kg vs. 18.2 kg) and develop histological evidence of myopathy. Thus, continued alcohol abuse was generally reflected in deterioration of muscle strength and the appearance of histological injury to muscle. Importantly, almost half of the sober patients did not recover to normal levels, indicating that alcoholic myopathy is only partially reversible. We also unexpectedly found that, in some alcoholics, a substantial reduction in the amount of alcohol consumed may be as effective as complete abstinence in improving muscle strength or preventing its deterioration.     

Correction to Fortier et al. (2008).

Reports an error in "Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics" by Catherine Brawn Fortier, Elizabeth M. Steffen, Ginette LaFleche, Jonathan R. Venne, John F. Disterhoft and Regina E. McGlinchey (Neuropsychology, 2008[Mar], Vol 22[2], 196-208). The lifetime drinking data listed in Table 1 on p. 198 was not correctly calculated and underestimated lifetime exposure to alcohol. The corrected lifetime variables from that table are included. (The following abstract of the original article appeared in record 2008-02526-007.) Evidence has shown that alcoholism leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment in simple forms of EBCC, whereas changes in forebrain structures result in impairment in more complex tasks. In this study, the ability of abstinent alcoholics and matched control participants to acquire learned responses during delay discrimination and discrimination reversal was examined and related to severity of drinking history and neuropsychological performance. During discrimination learning, one tone (CS+) predicted the occurrence of an airpuff (unconditioned stimulus), and another tone (CS-) served as a neutral stimulus; then the significance of the tones was reversed. Alcoholics who learned the initial discrimination were impaired in acquiring the new CS+ after the tones reversed; this is a function that has previously been linked to forebrain structures. It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conceptual shifting in chronic alcoholics.

Examined the inferior performance of chronic alcoholics on abstracting tasks. After, administering the Wisconsin Card Sorting Test to 24 alcoholics, it was found that alcoholics took more trials to reach criterion and made more errors than either a group of 24 hospital controls or 24 students. Error pattern analysis indicates that these differences could not be attributed to perseveration. The deficit appeared to be in sustaining a pattern of search and persistence in problem solution. Duration of drinking history was related to impairment of task persistence. Results are consistent with the hypothesis of subcortical organic involvement with a concomitant deficit in conceptual shifting tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chlorzoxazone pharmacokinetics as a marker of hepatic cytochrome P4502E1 in humans

OBJECTIVE: Previous in vitro studies have demonstrated that hepatic P4502E1 metabolizes chlorzoxazone (CZX, a commonly used muscle relaxant) to 6-hydroxychlorzoxazone (6-OH-CZX). We thus assessed whether measurement of the plasma 6-OH-CZX/CZX ratio after a CZX challenge could serve as a marker of hepatic P4502E1 content. METHODS: Three subject groups were included: recently drinking alcoholics (N = 6), abstinent alcoholics (N = 5), and nonalcoholic subjects with liver disease (N = 5) undergoing liver biopsy. Excess tissue was procured for immunochemical determination of hepatic P4502E1 content. Within an hour of the biopsy, 750 mg CZX was administered orally and serial plasma samples were collected for 6 h. RESULTS: Recently drinking alcoholic subjects had a higher area under the curve for plasma 6-OH-CZX (1.354 +/- 0.258 microg x min x ml(-1)) then abstinent alcoholic subjects (0.296 +/- 0.080 microg x min x ml(-1), p < 0.005) and subjects with nonalcoholic liver disease (0.428 +/- 0.061 microg x min x ml(-1), p < 0.005). The use of the plasma 6-OH-CZX/CZX ratio at 90, 120, and 180 min discriminated between recently drinking alcoholic and nondrinking subjects. Hepatic P4502E1 content significantly correlated with the maximal 6-OH-CZX concentration (r = 0.76, p = 0.001) and other pharmacokinetic parameters. In the recently drinking group, the area under the curve for plasma 6-OH-CZX significantly decreased after 8 days of abstinence. CONCLUSIONS: Measurement of plasma 6-OH-CZX after administration of a CZX challenge can serve as a marker of hepatic P4502E1 activity and thus help avoid adverse drug reactions secondary to P4502E1 induction, particularly in heavy drinkers.     

25-hydroxy vitamin D deficiency with reduction of intestinal calcium absorption and bone density in chronic alcoholism

Plasma levels of 25-hydroxycalciferol (25-OH-D), 47-calcium intestinal absorption, bone mineral content and the biologic parameters of phospho-calcium metabolism were studied in 30 chronic alcoholics, 15 with Laennec's cirrhosis (group A) and 15 without (group B). These patients were compared with 27 normal subjects. In group A, the mean 25-OH-D plasma level was 23.7 +/- SD 18.5 microgram/l and in group B 35.2 +/- SD 21.8 microgram/l. These mean levels were lower than those of the control group, which were 57.2 +/- SD 22.5 microgram/l (p less than 0.001). The mean value of the 47Ca intestinal absorption, measured as the percentage of the ingested dose per litre of plasma and multiplied by the body weight, was also significantly lower in group A, which was 140 +/- SD 47 (p less than 0.01), and in group B, which was 145 +/- SD 69 (p less than 0.05), compared with the normal subjects whose average was 182 +/- SD 45.6. Similarly, the total plasma calcium was low: 1.99 +/- SD 0.24 mmol/l in all the alcoholics, while that of the control group was 2.22 +/- SD 0.18 mmol/l (p less than 0.001). For the 30 chronic alcoholics there was a positive correlation between 25-OH-D and 47Ca intestinal absorption, (r = 0.484; p less than 0.004). This suggests that in chronic alcoholism the deficiency of 25-OH-D induces a diminution of the intestinal absorption of calcium which, in the long term, can result in bone demineralization evidenced in the patients studied by a bone mineral content lower than normal (p less than 0.001).     

Dawn simulation treatment of abstinent alcoholics with winter depression

BACKGROUND: Recent data suggest that winter depression (seasonal affective disorder [SAD]) may be a subtype of affective disorder that is closely related to alcoholism. Dawn simulation has been shown in controlled trials to be effective in SAD. The present study examined the effectiveness of dawn simulation in abstinent alcoholics who met DSM-III-R criteria for major depression, or bipolar disorder, depressed with seasonal pattern. METHOD: All 12 subjects with winter depression had a history of either alcohol dependence or alcohol abuse according to DSM-III-R and had been abstinent from alcohol for at least 6 months. They also fulfilled criteria for SAD according to Rosenthal and were hypersomnic and drug free. After a 1-week baseline period, the subjects were randomly assigned to a 1-week treatment period at home with either a white 1.5-hour dawn from 4:30 a.m. to 6:00 a.m. peaking at 250 lux or a red 1.5-hour dawn from 4:30 a.m. to 6:00 a.m. peaking at 2 lux. The subjects were told that they would receive daily either a red or a white dawn reaching the same illuminance, an illuminance that would be much dimmer than standard bright light treatment. At the end of each week, the subjects were blindly assessed by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder version (SIGH-SAD). RESULTS: For the 6 subjects completing the white dawn treatment, the mean SIGH-SAD score decreased from 33.0 at baseline to 15.8 after treatment. For the 6 subjects completing the dim red dawn treatment, the mean SIGH-SAD score decreased from 34.3 to 32.7. The mean post-dawn SIGH-SAD score was significantly lower after the white dawn treatment than after the dim red dawn treatment (ANCOVA with baseline SIGH-SAD as the covariate, F = 12.95, p < .01). Superiority of the white dawn was also found by analogous analyses for the Hamilton Rating Scale for Depression (HAM-D) (p < .01) and the SAD Subscale (p < .05). CONCLUSION: The present study suggest that dawn simulation may be helpful in decreasing depression in abstinent alcoholics with SAD. Further study is necessary to confirm these preliminary findings and to determine whether dawn simulation might be helpful in preventing relapse in abstinent alcoholics who have SAD.     

Cue exposure with coping skills treatment for male alcoholics: A preliminary investigation.

Although early investigations were promising, no controlled follow-up studies have investigated the effectiveness of cue exposure treatment for alcoholics. In this study, inpatient alcoholics received either cue exposure integrated with urge coping skills training (CET; n?=?22) or a contrast condition (CC) involving daily contact with assessment only (n?=?18) in addition to standard treatment. Comprehensive assessment measures were used to investigate change in process and outcome variables. In the 2nd 3 mo after treatment, the CET group included more patients who were completely abstinent, had a higher percentage of abstinent days, and tended to report fewer drinks per day than did patients in the contrast condition. The significantly greater use of coping skills during follow-up by the CET group and the significant relationship of these coping skills to decreased drinking suggest that treatment effects were due, at least in part, to the coping skills training, consistent with recent formulations. Theoretical and treatment implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep-disordered breathing in alcoholics: association with age

Sleep apnea and related disorders are not uncommon in abstinent alcoholics. We assessed the relationship between age and the presence and severity of sleep-disordered breathing in alcoholism by performing one night of polysomnography on 75 abstinent alcoholic subjects undergoing treatment for alcoholism. Sleep-disordered breathing (defined as 10 or more apneas plus hypopneas/hr of sleep) was present in 17% of 66 men aged 22-76 and in 0 of 9 women aged 28-63 years. Three percent of men under age 40 years had sleep-disordered breathing compared with 25% of men between ages 40-59 and 75% of those above age 60. Although alcoholics with sleep-disordered breathing had a higher body mass index than those without, the increased frequency over age 40 was statistically significant after controlling for the effects of body mass index. Sleep in subjects with sleep-disordered breathing was significantly more disturbed than in subjects without sleep-disordered breathing. Our findings suggest that sleep-disordered breathing in older male alcoholics is more prevalent than has been reported in most studies of normal men and that the increase in sleep-disordered breathing that occurs with age in alcoholics is greater than the age-related increase in sleep-disordered breathing that occurs in healthy elderly men. Furthermore, sleep-disordered breathing is a significant contributor to sleep disturbance in a substantial proportion of male alcoholics above the age of 40 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coping methods and reasons for not drinking

Methods for coping with stress and reasons for not drinking were examined among abstinent alcoholics to determine whether change occurred with length of sobriety. Results showed that 1) alcoholics with briefer abstinence relied more heavily on coping methods, 2) alcoholics relied less on negative than positive coping methods regardless of length of sobriety, and 3) the number and types of reasons for not drinking did not vary with length of sobriety, rather, several positive reasons for not drinking continued as motivators. Concerning coping methods, the authors speculate that as alcoholics remain sober longer, coping methods become less important or automatic and less conscious.     

Verbal and visuospatial performance in male alcoholics: A test of the premature-aging hypothesis.

Tested the premature-aging hypothesis of generalized dysfunction, using a paired-associate learning test that has separate verbal and visuospatial subtests of the same structure and method. Ss were 36 hospitalized White male chronic alcoholics (mean age 42.4 yrs), 36 control Ss (mean age 42.5 yrs), and 24 elderly Ss (mean age 71.4 yrs). Ss were also administered the Shipley Institute of Living Scale for Measuring Intellectual Impairment and Memory-for-Designs test. Results show that elderly control Ss performed significantly worse than middle-aged control Ss on both learning subtests. For Ss between 30 and 80 yrs of age, increasing age resulted in increasing errors. According to the generalized dysfunction hypothesis, the performance of alcoholics should be similar to that of the elderly, showing impairment compared to control Ss on both learning tests. However, alcoholics performed at the same level as the middle-aged control Ss on verbal learning and were significantly poorer on visuospatial learning. The generalized dysfunction version of the premature-aging hypothesis for performance of alcoholics on neuropsychological tests was not supported. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mitochondrial aspartate aminotransferase isoenzyme: a biochemical marker for the clinical management of alcoholics?

Serum mitochondrial and total aspartate aminotransferase activity was quantified by a characterized immunochemical method in 126 subjects, 44 healthy controls and 82 chronic alcoholics (51 outpatients and 31 monitored through 15 days). The monitored alcoholics were divided into actual abstinents (n = 21) and drinkers (n = 10) by blood ethanol concentration performed daily. The aims of the present study were: (a) to compare the diagnostic diagnostic usefulness of the mitochondrial isoenzyme and the mitochondrial/total aspartate aminotransferase ratio to detect problematic drinkers; (b) to evaluate the suitability of these indices to monitor abstinence, a difficulty not yet solved in the clinical management of alcoholics. The results demonstrated the mitochondrial isoenzyme to be more suitable to discriminate between controls and alcoholics (Kruskal and Wallis ANOVA, Bonferroni test, P < 10(-5) and mostly between actual drinkers and other alcoholics (P < 0.041). So acute alcohol consumption may be a significant, suggestive and until now inadequately examined factor in evaluating the suitability of mAST as a marker. The results, showing that mAST peaks quickly appear in the presence of a new alcohol intake, should indicate mAST as a possible marker of acute alcohol intake useful in checking self-claimed abstinence.     

Selective processing of visual alcohol cues in abstinent alcoholics: an approach-avoidance conflict?

When symptomatic individuals selectively attend to emotionally relevant stimuli, the ability to shift attention away from such material is impaired. Subjects may, however, seek to avoid further processing of these stimuli, which would facilitate attentional shifts. This was examined in a group of abstinent alcoholics' responses to stimuli related to alcohol. Eight alcohol and eight neutral words served as cues in a covert attention task. The cues were either valid (2/3 of trials) or invalid (1/3 of trials) indicators of where a response target would appear after 100 or 500 milliseconds. The short interval was expected to interact with an initial approach toward the alcohol word, while the long interval would interact with a subsequent avoidance of the stimulus. As predicted, the alcoholics showed slower reaction times (RTs) to targets invalidly cued by alcohol words in the short interval, reflecting increased difficulties to shift attention. However, the alcoholics demonstrated faster RTs to targets invalidly cued by the alcohol words in the long interval. This indicates that the alcohol cue elicited emotional associations that, subsequent to initial stimulus identification, trigger an interrupting function of the attentional system.     

Selective attention, breadth of attention, and shifting attention in chronic nonparanoid schizophrenics

Compared the performance of 16 normals (hospital employees), 16 chronic schizophrenics, and 16 hospitalized alcoholics in a reaction time task with simultaneous presentation of 2 stimuli and the offset of 1 stimulus as the signal. The stimuli were either of 1 or 2 different modalities, and the signal was known or was not known to the Ss in advance. The data were analyzed according to 2 different models of attentional deficit in chronic nonparanoid schizophrenics. No empirical support could be found for W. E. Broen's (1973) model, which attributes the difficulties that chronic nonparanoid schizophrenics experience in tasks with stimuli of different sense modalities to narrowed attention. On the other hand, M. W, Kristofferson's (see PA, Vol 42:958) findings on slower attentional shifts in chronic schizophrenics could be replicated. As an extension of her work, it is shown that this slower shifting process is confined to cross-modal shifts—no differences being found between normals, chronic schizophrenics, and alcoholics in ipsimodal shifts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cost effectiveness of alcoholism treatment in partial hospital versus inpatient settings after brief inpatient treatment: 12-month outcomes.

174 alcoholics (mean age 41.37 yrs) were randomly assigned to partial hospital treatment (PHT) or extended inpatient (EIP) rehabilitation after inpatient evaluation and/or detoxification. 12-mo follow-up results for the 115 Ss who consented to continue in the study show few differences in clinical outcomes between the PHT and EIP groups. Both reported more than 80% abstinent days during follow-up, and over 70% had a full-time occupational role, although almost a third experienced job losses during the year. Ss showed significant improvements in psychological well-being and social behavior. One-third were rehospitalized during the follow-up year. Costs for the PHT group were significantly lower than the EIP group, leading to an overall conclusion that PHT provides a cost-effective alternative to EIP treatment for many alcoholics. Implications for health care planning are addressed. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of alcoholics' self-reports of drinking behavior with reports of collateral informants.

Collected 6-mo posthospitalization follow-up data from 52 alcoholics and their collateral informants. Ss' self-reports and collateral reports of Ss' drinking were highly correlated when Ss had been either mostly abstinent or mostly drunk throughout the follow-up period. Findings suggest that (a) alcoholics who have been hospitalized for detoxification generally provide reliable self-reports of their posttreatment drinking behavior, and (b) gathering data from collateral informants is an effective method for corroborating alcoholics' self-reports of drinking behavior. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Altered motor control in chronic alcoholics.

Compared the performance of 48 male chronic alcoholic patients and 48 nonalcoholic medical patients on a test of motor control (turning a knob as slowly as possible) and other tasks (e.g., time estimation). Results show that alcoholics turned the knob significantly faster than nonalcoholics. The differences between groups were greatest when Ss performed with eyes closed. The difference in knob-turning can not be accounted for by performance on the other tasks; alcoholics showed visual-spatial difficulties, muscle weakness, hand tremor, and subjective-time overestimation. In addition, impaired control was found in both hands and on a slow line-drawing test. 2 possible neuropsychological explanations are advanced to account for the alcoholics' performance: (a) damage to the frontal-limbic diencephalic circuit resulted in disrupted inhibitory motor control, and (b) right hemisphere damage interfered with utilization of kinesthetic-proprioceptive information in the feedback control of motor behavior. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)