Blackouts: relationship with memory capacity and alcoholism history.

Male alcoholic inpatients with a high incidence of memory blackouts did not differ on several memory measures from subjects with a low incidence of blackouts. Alcoholism chronicity also did not differentiate between subjects on the Wechsler Memory Scale, tests of storage and decay of a memory trace, and maintenance of a concept along a temporal continuum. A history of blackouts was, however, related to drinking pattern. High-incidence subjects reported a significantly greater frequency of drinking to intoxication or until falling asleep, craving a drink, and increased tolerance to alcohol.

Differentiation of alcoholics. Childhood history of minimal brain dysfunction, family history, and drinking pattern.

Alcoholics were differentiated into two subgroups on the basis of drinking patterns and subjective response to alcohol. Severe drinkers (primary alcoholics) retrospectively reported more symptoms of childhood minimal brain dysfunction than less severe drinkers (secondary alcoholics), psychiatric patients, and normals. The alcoholics as a group reported a greater incidence of familial alcohol abuse than the psychiatric subjects, but a difference on this factor was not observed between the primary and secondary subgroups. In terms of clinical status, the primary alcoholics presented Minnesota Multiphasic Personality Inventory profile more indicative of normality than the other groups, but scored significantly higher on the MacAndrew Alcoholism Scale. These findings are discussed in light of further delineating a specific subtype of alcoholism that may have a genetic-constitutional relationship with other pathological disorders.

Severity of hepatic encephalopathy before liver transplantation is associated with quality of life after transplantation.

BACKGROUND: Cirrhosis is associated with a chronic low-grade hepatic encephalopathy and disturbances in quality of life. This study investigated the extent to which severity of hepatic encephalopathy before orthotopic liver transplantation correlated with quality of life. METHODS: A battery of neuropsychological tests was administered to nonalcoholic patients to quantify severity of hepatic encephalopathy. The Sickness Impact Profile was administered before and after surgery to document quality of life across multiple health and psychosocial dimensions. RESULTS: There was substantial improvement from the pretransplant to the posttransplant periods across almost all dimensions of quality of life. Neuropsychological test scores explained up to 20% of the variance in magnitude of change from pre (before) to post (after) surgery. CONCLUSION: Severity of hepatic encephalopathy (particularly with respect to static ataxia and fine motor control) is associated with posttransplantation improvement in quality of life.

Quality of life before and after orthotopic hepatic transplantation.

Fifty-three nonalcoholic patients were evaluated prior to liver transplantation and again approximately 3 years after surgery using the Sickness Impact Profile and Social Behavior Adjustment Schedule. Test-retest scores reflected significant improvement across all health and psychosocial scales of the Sickness Impact Profile. On the Social Behavior Adjustment Schedule, significant improvement was observed on scales measuring disturbed behavior, social role performance, and burden. Comparisons between groups indicated that the liver transplant patients were still impaired on eight of the Sickness Impact Profile scales after transplant; however, the severity of disturbance was not considered to be clinically significant. No between-group differences were noted on the Social Behavior Adjustment Schedule. These results indicate that liver transplantation is associated with substantial improvement in life quality, although as a group, the patients undergoing this surgery do not recover to the level of functioning demonstrated by normal individuals.

Neuropsychological findings relating to Capgras syndrome.

A 37-year-old female with Capgras syndrome was assessed on psychometric and neuropsychological measures. Significant neuropsychological deficits suggesting a frontal-temporal cerebral dysfunction were observed. The results demonstrate that the Capgras delusion involves more than an inability to recognize faces, although this deficit is one manifestation of the disorder.

Plasma GABA-like activity in response to ethanol challenge in men at high risk for alcoholism.

Sons of alcoholic fathers (high risk, HR) and matched control men from families without alcoholism (low risk, LR) were administered, in a randomized double-blind fashion, either a placebo beverage or an isovolemic beverage containing ethanol (0.8 g/kg). Serial blood sampling for determination of plasma gamma-aminobutyric acid (GABA)-like activity, mood, and intoxication ratings were performed. The HR subjects were found to have significantly less plasma GABA-like activity than LR during the placebo condition. The alcoholic beverage condition washed out the differences in plasma GABA between groups. Significant interactions between risk group status and beverage conditions were found with respect to plasma GABA-like activity. Alcohol produced an increase in mean GABA-like activities among HR subjects, whereas a slight decline was noted among LR subjects. Plasma GABA-like activity also had a significant inverse correlation with self-reports of perceived tension in the placebo condition, and tension, confusion, and intoxication in response to the alcoholic drink. Since previous investigators have reported reduced plasma GABA levels in alcoholic individuals, reduced plasma GABA-like activity may be a biological marker for vulnerability to alcoholism or for heightened tension as a behavioral factor that predisposes to alcoholism.

Heightened motor activity level in male offspring of substance abusing fathers.

Heightened activity level has been implicated in the liability for substance abuse, but no prior research has directly examined motor activity in a sample of prepubertal boys at high-risk for substance abuse. The magnitude of behavioral activity of 10-12 year-old sons of substance abusing fathers (SA +) (n = 42) and controls (SA -) (n = 60) was assessed using a microprocessor-based activity monitor during tasks that demanded significant concentration, effort, and constraint on motor activity, and when no such demands were present. Psychiatric status, measures of temperament traits, and measures of internalizing and externalizing behaviors were also obtained on the boys. Although the groups did not differ during the lower demand task, SA + boys showed significantly greater motor activity than SA - boys during the tasks that required concerted effort, attention, and behavioral suppression. Multiple regression analysis indicated that under the low-demand condition, the presence of an anxiety disorder in the boy was the only significant predictor of activity level. However, under the conditions that demanded effort, concerted attention and behavioral suppression, SA + group membership, and having low rhythmicity (as a temperament trait) predicted heightened activity. Statistically controlling for rhythmicity, the SA + boys were estimated to have about 24% higher activity than control boys. The results suggest that heightened motor activity may be associated with susceptibility to substance abuse.

Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary cirrhosis.

The purpose of this study was to determine the prevalence of vitamin E deficiency in adults with chronic cholestatic liver disease and to quantify the association between their psychomotor performance and vitamin E status. In 42 female patients with primary biliary cirrhosis, 43.5% met two standard criteria for vitamin E deficiency. Vitamin E-deficient patients performed less well than did healthy control subjects on six of eight neuropsychologic tests of psychomotor capacity (p less than 0.01). Vitamin E-sufficient patients did not differ significantly from normal control subjects. Serum vitamin E concentrations were significantly lower in the group classified as significantly psychomotor-impaired by two independent neuropsychologists (blind to vitamin E status) whereas liver-injury measures failed to distinguish between these two groups. Patients with low serum vitamin E exhibited clinically evident neurologic abnormalities. These data suggest that vitamin E deficiency may, in part, underlie psychomotor and neurologic disturbance found in adult patients with chronic cholestatic liver disease.

Subclinical hepatic encephalopathy. Comparison before and after orthotopic liver transplantation.

Sixty-two patients were evaluated before and after liver transplantation on a battery of neuropsychologic tests measuring hepatic encephalopathy. Compared to controls, deficits were found on tasks measuring memory and visuospatial capacity prior to transplantation. Most of these deficits were ameliorated following the surgery. It is concluded that functional psychological capacity is restored to a large extent, but not completely, following orthotopic liver transplantation.

Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse.

An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with "long" alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted.

Antisociality, substance dependence, and the DRD5 gene: a preliminary study.

A pilot population-based study of a microsatellite polymorphism at the DRD5 locus in adult European-Americans showed its association with childhood symptom counts for oppositional defiant disorder (ODD) in males and females and adult antisocial personality disorder (ASPD) in females. No association with childhood conduct disorder symptom count was observed. ODD mediated the genotype-ASPD relationship in females. Neither ODD nor ASPD significantly mediated the relationship between the genotype and the liability to substance dependence (SD). The data suggest involvement of the DRD5 locus in the variation and sexual dimorphism of SD liability and antisociality and in the developmental continuity of antisociality.

Impact of liver disease on daily living in transplantation candidates.

The impact of different types of liver diseases on life quality in transplantation candidates was assessed. For all disease types, psychosocial impairment exceeded physical impairment. Among the various disease conditions, differences on the pattern and severity of life quality disturbances were observed.

Comparison between treatment completers and noncompleters among dually diagnosed substance-abusing adolescents.

The psychiatric and demographic characteristics that may distinguish treatment completers from noncompleters among hospitalized adolescents with substance abuse and comorbid psychiatric disorders were examined. Affective and adjustment disorders were more prevalent among treatment completers whereas non-completers were more likely to be assigned a conduct disorder diagnosis. There were no differences between the groups with respect to demographic and legal status, education level and lifetime psychiatric diagnosis in the parents or caretakers, living arrangements, treatment history, and perception of treatment benefits. A higher percentage of treatment completers than noncompleters received psychotropic medications. The factors contributing to treatment termination as well as the clinical and research implications of the findings are discussed.

Association between hyperactivity and executive cognitive functioning in childhood and substance use in early adolescence.

OBJECTIVE: To determine whether deficient executive cognitive functioning (ECF) in association with high behavioral activity level comprise components of the liability to substance abuse. METHOD: A high-risk (HR) group having fathers with a lifetime DSM-III-R diagnosis of a psychoactive substance use disorder was compared with a low-average-risk (LAR) group whose fathers had neither psychoactive substance use disorder nor another adult Axis I psychiatric disorder. ECF and behavioral activity were measured using neuropsychological tests, activity monitor, diagnostic interview, and informant ratings when the subjects were 10 to 12 years of age. Alcohol, tobacco, and cannabis use were measured at 2-year follow-up. RESULTS: At baseline, the HR group had a significantly higher behavioral activity level and exhibited poorer performance on ECF tests than the LAR group. By early adolescence, HR subjects had a higher lifetime rate of tobacco and cannabis use and earlier age at onset of cannabis use. ECF capacity, but not behavioral activity level, predicted tobacco and cannabis use, total number of drugs ever tried, and severity of drug involvement. ECF accounted for additional variance beyond the effects of conduct problems on these outcomes. CONCLUSION: Whereas behavioral activity and ECF capacity in late childhood distinguishes HR from LAR youth, childhood ECF capacity is the more salient predictor of drug use in early adolescence.

Alcoholism: a developmental disorder.

Alcoholism etiology is discussed from a developmental behavior genetic perspective. At the outset point, temperament characteristics, by means of ongoing and reciprocal interaction with the social environment, shape the course of behavioral development. The behavioral characteristics successively acquired during development are vectors that determine the ontogenetic trajectory that culminates ultimately in the clinical disorder of alcoholism. The temperament features that appear to be associated with a heightened risk for alcoholism are examined. Their interactions with the environment during the course of development are considered within an epigenetic framework and, as discussed, have important ramification for improving the prevention and treatment of alcoholism.

Sensory information processing in patients with nonalcoholic cirrhosis. Short-latency visual, auditory, and somatosensory event-related potentials.

Visual, auditory and brainstem event-related potentials were obtained from patients with hepatocellular and cholestatic disease and a control group of normal subjects. The results did not reveal systematic neurophysiologic disturbances in persons with well compensated cirrhosis. It is concluded that short-latency event-related potentials are rather insensitive for detecting subclinical hepatic encephalopathy.

Executive cognitive functioning, temperament, and antisocial behavior in conduct-disordered adolescent females.

The authors assessed whether low executive cognitive functioning (ECF) and a difficult temperament are related to aggressive and nonaggressive forms of antisocial behavior (ASB) in 249, 14-18-year-old, conduct-disordered females and controls. ECF was measured using neuropsychological tests; temperament was measured using the Dimensions of Temperament Survey-revised; and ASB was assessed using psychiatric symptom counts for conduct disorder. The conduct-disordered females exhibited lower ECF capacity and a greater difficult temperament compared with the controls. The combined influence of low ECF and difficult temperament was significantly related to both forms of ASB. In comparison with low ECF, difficult temperament was more strongly related to nonaggressive ASB, whereas in comparison with difficult temperament, low ECF was more strongly related to aggressive ASB. Last, ECF mediated the relation between difficult temperament and aggressive ASB.

Genetic studies of substance abuse.

Genetic studies of substance abuse indicate that variation in the risk for the disorder in the population is contributed by differences in both individual genotypes and environment. Recent developments in genetics raise the possibility of disentangling the complex system of genotype-environment interaction that determines the development of the individual behavioral phenotype. This paper reviews the concepts, methods and results pertaining to genetic investigation of substance abuse.

Behavioral self-regulation: correlates and 2 year follow-ups for boys at risk for substance abuse.

This investigation demonstrated the heuristic construct of behavioral self-regulation (BSR) as a salient component of the liability to substance abuse. Three dimensions of childhood behaviour were employed to create a dimensional model of BSR: inattention, impulsivity/hyperactivity and aggressivity. Multiple measures and multiple informants were employed to develop indices of the three traits in a sample of 10-12 year old sons of substance abusing fathers (high risk (HR); n = 180) and normal controls (low average risk (LAR); n = 200). Informants included mothers, boys and their teachers. The results confirmed the presence of a first-order latent trait of BSR. HR boys had significantly higher scores on BSR than LAR boys. Concurrent validity of the BSR trait scores was supported by significant associations with measures of family dysfunction, deviant peer affiliations and poor school performance. These latter problems are commonly prodromal to substance abuse. Predictive validity of the BSR trait baseline scores (age 10-12 years) was supported at 2 year follow-up by significant associations of BSR scores with magnitude of deviant peer affiliations; trends toward significance were found for family dysfunction and poor school performance. Taken together, these results confirm and extend previous findings which indicate that poor BSR is prodromal to substance abuse.

Adolescent versus adult onset and the development of substance use disorders in males.

This study examines the influence of adolescent age of onset on the development of substance use disorders (SUD) by comparing adult males (n = 181) with SUD categorized into adolescent-onset, early-adult onset and late-adult onset groups on patterns of substance use and related disorders, time course of the development of substance dependence and rates of comorbid mental disorders. A sample of male adolescents (n = 81) with SUD was also included as a comparison group. The subjects were recruited from intervention programs in the community and participated in semistructured interviews with diagnoses determined by the best estimate method. Adolescent-onset adults, compared with other adult-onset groups, had higher lifetime rates of cannabis and hallucinogen use disorders, shorter times from first exposure to dependence, shorter times between the development of their first and second dependence diagnoses and higher rates of disruptive behavior disorders and major depression. Adolescents were similar to adolescent-onset adults. While the findings must be interpreted in light of methodological limitations, these results suggest that adolescent-onset SUD is a distinct subtype involving different substances and more rapid development than adult-onset SUD.