Cognitive Functioning, ASP, and Family History of Alcoholism in Young Men at Risk for Alcoholism

Previous research has suggested that individuals with a family history of alcoholism may have cognitive deficits that predate, and possibly predispose, to the onset of alcoholism. However, these deficiencies may result from other factors, e.g., comorbid psychopathology. The current study investigated the neuropsychological functioning of young adult males at high risk for alcohol abuse due to a family history of alcoholism (FH) and/or a personal history of antisocial personality disorder (ASP). A family history of alcoholism (FH+) alone was not associated with neuropsychological impairment. Subjects with ASP, however, exhibited some difficulty with higher level motor control and with verbal concept formation compared with nonASP subjects. No clear pattern of FH x ASP interaction was evident in the measures examined. These findings suggest that previous findings suggesting cognitive deficiencies in FH+ individuals may have been related to a failure to consider co-morbid ASP. The deficits exhibited by the ASP subjects may reflect both reduced inhibitory control and a deficiency in higher level verbal skills. These deficiencies may leave ASP individuals less capable of utilizing higher level language skills to regulate behavior.     

Adrenocortical Responses and Family History of Alcoholism

BACKGROUND: This study was designed to assess whether nonalcoholic offspring from families with a high density of alcohol-dependent individuals have altered hypothalamic-pituitary-adrenal (HPA) axis dynamics compared with nonalcoholic subjects without a family history of alcohol dependence. METHODS: Seventy-eight nonalcoholic subjects aged 18 to 25 were enrolled in the protocol. Thirty-nine subjects were offspring from families with a high density of alcohol dependence and were designated as family history-positive (FHP) subjects. Thirty-nine subjects were biological offspring of nonalcohol-dependent parents and were designated as family history-negative (FHN) subjects. Subjects received naloxone hydrochloride (0 and 125 microg/kg) and cosyntropin (0, 0.25 microg, and 250 microg) in double-blind, randomized order and cortisol was monitored. A subset of subjects (11 FHP, 11 FHN) was admitted to the General Clinical Research Center to measure serum cortisol levels every 30 min for 24 hr. RESULTS: FHP subjects had an increased cortisol response to opioid receptor blockade induced by naloxone. However, no group differences in cortisol were uncovered during administration of cosyntropin or during monitoring of the cortisol circadian profile. CONCLUSION: These observations suggest that differences in the cortisol dynamics between FHP and FHN subjects are unmasked by opioid receptor blockade directed at the hypothalamus, but not when cortisol levels are directly provoked at the level of the adrenal gland. In addition, unprovoked cortisol secretion monitored over a 24-hr interval cannot distinguish FHP from FHN subjects.     

Influence of Family Alcoholism History on Alcohol Metabolism, Sensitivity, and Tolerance

As part of the Colorado Alcohol Research on Twins and Adoptees (CARTA), 35 subjects who reported having an alcoholic parent or sibling [family alcoholism history positive (FHP)] were matched with 35 controls [family alcoholism history negative (FHN)]. All subjects were tested three times on a battery of physiological, motor, and cognitive performance tasks before the ingestion of alcohol, then were tested three more times over a 3-hr period during which their blood alcohol concentration (BAC) was brought up to and maintained at about 0.10 g/dl by an initial large dose of ethanol and subsequent topping doses. FHP subjects scored significantly lower than FHN subjects on the Raven's Progressive Matrices and on some of the cognitive tasks before alcohol ingestion. FHP and FHN subjects, however, did not significantly differ in absorption and clearance of alcohol or in sensitivity and acute tolerance scores calculated on the repeated measures. Contrary to expectations, FHP subjects perceived themselves as being more impaired by alcohol than FHN subjects, and there was little evidence to suggest that they were less sensitive to variations in BAC.     

Event‐Related Oscillations Versus Event‐Related Potentials in a P300 Task as Biomarkers for Alcoholism

Objective: It has been proposed that event‐related oscillation (ERO) measures of EEG activity recorded in P300 tasks provide more powerful biomarkers of alcoholism than event‐related potential (ERP) measures. This study examines this question in a group of long‐term abstinent alcoholics (LTAAs). Methods: EEGs were recorded on 48 LTAAs and 48 age and gender‐matched nonalcoholic controls (NACs) during the performance of a 3‐condition visual target detection task. The event‐related data were analyzed to extract ERP amplitude measures and total and evoked ERO power measures. Data were analyzed using multivariate analysis of covariance to determine the contributions of ERO versus ERP measures to discriminate between the LTAA versus NAC groups. Results: The LTAA group showed significantly lower evoked δ ERO power and total δ and θ ERO power compared to the control group. The evoked and total ERO power measures provide an alternative (but not more powerful) representation of the group difference than does P3b amplitude. There was a weak suggestion that nonphase‐locked θ ERO power (which contributes to total ERO power) might provide independent discriminatory information. Conclusions: Reduced evoked ERO power in the response to target stimuli provided an alternative and comparable representation of the reduced P3b amplitude in LTAA. This is not surprising as the evoked ERO power measures are derived from time‐frequency representations of the ERP waveform. Induced theta oscillations might provide independent discriminatory information beyond ERP amplitude measures, but separate analysis of the event‐related nonphase‐locked activity is required to investigate this further.     

Biases in the Diagnosis of Alcoholism by the Family History Method

The authors explored the factors influencing the agreement of diagnoses of alcoholism obtained by a best-estimate (BE) procedure versus those obtained by family history (FH) only, based on data from the Roscommon Family Study. The participants were first-degree relatives of either schizophrenic subjects, subjects with affective disorders, or matched community controls. The FH information was obtained from first-degree relatives of the participants, whereas the BE diagnoses included personal interview and medical records as well as FH information. Two types of error were distinguished: false-negative FHs, who were diagnosed with alcoholism by BE but not by FH; and false-positive FHs, who were diagnosed with alcoholism by FH but not by BE.
The risk of false-negative FHs was increased by young age of the subject and male gender of the informant, and decreased by a history of previous hospitalization of the subject. Conversely, the risk for false-positive FHs was increased by older age of the subject, male gender of the subject, female gender of the informant, and informant's diagnosis of alcoholism. Comorbid diagnosis of nonaffective psychosis increased the risk of both types of error. It is concluded that when validated against a BE diagnosis, the FH diagnosis of alcoholism is subject to several biases and that the FH method is not a satisfactory substitute for BE diagnoses.     

Effects of Abstinence and Family History for Alcoholism on Platelet Adenylyl Cyclase Activity

Platelet adenylyl cyclase (AC) activity was measured in 32 alcohol-dependent subjects and 27 control subjects who were categorized as either family history-positive (FHP) or family history-negative (FHN) for alcoholism. The interview and blood sample collections were performed shortly after cessation of heavy drinking in the alcoholic group, and repeat blood samples were obtained at the end of the first and second weeks of monitored abstinence. Control subjects received the same interview and provided blood samples at the time of the interview. When subjects were not segregated for FHP or FHN status, there were no statistically significant differences in basal, cesium fluoride (CsF)-, orforskolin-stimulated mean AC activities between the controls and the alcoholics, at study entry or with 1 or 2 weeks of abstinence. On the other hand, over the 2-week course of sobriety from heavy drinking, the CsF-stimulated AC activity of FHP alcohol-dependent subjects decreased significantly (p = 0.03). FHP alcohol-dependent subjects after 2 weeks of sobriety had significantly lower mean CsF-stimulated AC activity than FHN controls (p = 0.04), whereas the FHN alcoholic subjects' CsF-stimulated AC activity did not differ significantly from FHN controls at this point in time. When all subjects were pooled and then categorized as either FHP or FHN, there was a significant difference in mean CsF-stimulated AC activity (p = 0.02) between the FHP and FHN subject groups. Genetic factors and abstinence appear to have roles in determining low platelet AC activity in alcoholic and nonalcoholic subjects. CsF-stimulated platelet AC activity, in particular, appears to act as a trait marker for a genetic vulnerability to developing alcoholism, but recent heavy drinking in male alcoholics is a factor that can mask differences between FHP and FHN subjects.     

Sensation Seeking, Stress Reactivity, and Alcohol Dampening Discriminate the Density of a Family History of Alcoholism

Data collected from 95 nonalcoholic men who had either a multigenerational (MFH), unigenerational (UFH), or negative family history (FHN) of alcoholism were subjected to a discriminant function analysis to determine how well a set of variables differentiated between the family history groups. The data-set comprised personality measures (sensation seeking scales, neuroticism, and extroversion), measures of cardiovascular reactivity to unavoidable shock, and measures of the cardiovascular reactivity-dampening effects of alcohol. The discriminant analyses correctly classified 62% of all subjects, 75% of MFH subjects, 47% of UFH subjects, and 63% of FHN subjects. A canonical discriminant function analysis revealed one significant dimension (canonical variable) that differentiated between family history groups. The high density (MFH) family group scored positively on this dimension, while the UFH and FHN groups had negative mean scores on this variable. A MFH of alcoholism was characterized by a pattern of increased sensitivity to the cardiovascular reactivity-dampening effect of alcohol, cardiovascular hyperreactivity to unavoidable shock when sober, and the personality characteristic of experience seeking, which is associated with a desire for novel and unconventional experiences.     

Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence

Empirical studies provide substantial evidence that having a family history of alcoholism increases the risk of developing alcohol dependence; however, some of this effect may be caused by nonspecific childhood socioeconomic adversity common in families with an alcohol-dependent parent. In this study, we examine joint effects of family history and childhood adversity within a sample of 509 men and 217 women over age 40. The measures analyzed were included in routine screening assessments for participants in various studies at the University of Michigan Alcohol Research Center. About 60% of the men and 45% of the women were alcohol-dependent. About 30% reported an alcoholic parent. Degree of family history affected drinking behavior for both men and women. There were also environmental effects on the same measures for both men and women. Childhood socioeconomic adversity was reported more frequently by participants with an alcoholic parent, but adversity effects were also shown for those with a negative family history. The risk of alcohol dependence was additively increased by a positive family history and childhood socioeconomic adversity. The environmental effects identified in this study are promising evidence for nonspecific factors that moderate family history risk for development of alcohol problems.     

Activation, Attention, and Visuospatial Learning in Adults With and Without a Family History of Alcoholism

While recent evidence shows visuospatial information processing deficits to be present in chronic alcoholics, it remains unclear whether such deficits are present prior to alcohol abuse in persons at risk for developing alcoholism. If present, it is also unclear whether the information processing mechanisms underlying these deficits are the same in alcoholics and persons at risk for alcoholism. This study investigated visuospatial information processing psychophysiological activation in adults with and without a family history of alcoholism. Thirty matched nonalcoholics served as participants. Fifteen persons were from families in which at least one biologic parent and one other relative had a history of alcoholism. Another group of 15 persons had no family history of alcoholism. In addition to displaying atypical patterns of learning-contingent physiological activation, participants with a family history of alcoholism displayed visuospatial learning that was significantly poorer than persons with no family history of alcoholism. The learning and physiological activation displayed by the participants with a family history of alcoholism were similar to those displayed by previously studied alcoholics using a similar learning task. The data suggest that visuospatial learning deficits may reflect an antecedent to, rather than a consequence of, chronic alcohol abuse.     

A Simple Auditory Oddball Task in Young Adult Males at High Risk for Alcoholism

The reduction in the amplitude of the auditory P300 in young adult males at high risk for alcoholism has not been as consistently replicated as has been the reduction in the visual P300 amplitude in the same group. The easier nature of the auditory task was thought to be responsible for the inconsistency. We examined the auditory P300 amplitude in a group that has not yet been studied, young adult sons of alcoholics (mean age = 24.9 years, n = 48), and compared them with age and sex-matched controls (mean age = 27.8 years, n = 23). We found the auditory P300 amplitude to be reduced in the high-risk group and this reduction to be the greatest over the posterior centro-parietal and occipital areas when individual leads were examined. We further analyzed the data using current source density, a mathematical transformation that circumvents some of the errors inherent in measuring scalp-evoked potentials, and found reduced current source density in the high-risk group in the posterior central and parietal areas. Thus, we found that a simple auditory oddball task was effective in eliciting P300 differences in groups at high and low risk for alcoholism. The clinical significance of the P300 is discussed, as well as the relevance of task difficulty in eliciting auditory P300 differences in young males at high risk for alcoholism.     

Effects of a Family History of Alcoholism on Autonomic,Neuroendocrine, and Subjective Reactions to Alcohol

The authors evaluated two groups of young nonalcoholic men with (n = 14) and without (n = 25) a family history of alcoholism (FH+ and FH?) in a single laboratory session, During the session, subjects drank either an alcoholic (0.5 ml/kg) or a nonalcoholic beverage. Neuroendocrine, cardiovascular, electrodermal, and self-report data were collected at multiple time points before and after beverage consumption. The data analysis revealed time-related changes in plasma cortisol, finger temperature, skin conductance level, and several of the self-report measures. Beverage-related changes were seen in finger temperature, plasma glucose, and self-reported fatigue. The only dependent measure to discriminate FH+ and FH- groups was plasma cortisol, which exhibited a more rapid decline over time in the FH+ group. The FH+/FH- group difference in plasma cortisol was neither enhanced nor reduced by alcohol.     

Analgesic Effects of Ethanol Are Influenced by Family History of Alcoholism and Neuroticism

Background: Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge. Methods: Forty‐eight healthy subjects participated in this study; thirty‐one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double‐blind, placebo‐controlled, randomized, within‐subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low‐exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high‐exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60‐minute infusion mark. Results: The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores. Conclusion: These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol.     

Temperament Deviation and Risk for Alcoholism

Sons of alcoholics and nonalcoholics drawn from a community sample were compared across multiple dimensions of temperament. Sons of alcoholics scored higher on only behavioral activity level. This trait score was found to be unrelated to family environment. The implications of these findings for clarifying alcoholism vulnerability are discussed.     

Priming Deficiency in Male Subjects at Risk for Alcoholism: The N4 During a Lexical Decision Task

Background:  While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics.
Method:  A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n  = 23] and nonalcoholic fathers [low risk (LR) n  = 28] to study whether the 2 groups differ in terms of the N4 component. Subjects were presented with 150 words and 150 nonwords. Among the words, 50 words (primed) were preceded by their antonyms (prime, n  = 50), whereas the remaining 50 words were unprimed. For the analysis, N4 amplitude and latency as well as behavioral measures for the primed and unprimed words were considered.
Results:  A significant interaction effect was observed between semantic condition and group, where HR subjects did not show N4 attenuation for primed stimuli.
Conclusion:  The lack of N4 attenuation to primed stimuli and/or inability to differentiate between primed and unprimed stimuli, without latency and reaction time being affected, suggest deficits in semantic priming, especially in semantic expectancy and/or postlexical semantic processing in HR male offspring. Further, it indicates that it might be an electrophysiological endophenotype that reflects genetic vulnerability to develop alcoholism.     

Alcohol and Drug Use by College Males as a Function of Family Alcoholism History

Family history of alcoholism increases the risk for development of alcoholism in male offspring. The present questionnaire study examined self-reported alcohol and drug use in 744 college males as a function of DSM-IIIR alcohol dependence diagnoses in first- and/or second-degree biological relatives. Substance use was most prevalent and most frequent in students with both first- and second-degree alcohol-dependent family members, was intermediate in students with only first-degree affected relatives, and was least in students with no affected relatives. Students with both first- and second-degree alcohol-dependent relatives reported: more alcohol, marijuana, sedative, and cocaine ingestion; a younger age at first alcohol intoxication and first marijuana use; experience with less commonly used drugs; and more personal substance-related problems as well as more family mental health care. These data have significant prevention implications for targeting at-risk youth.     

Gender Differences in the Brain: Implications for the Study of Human Alcoholism

Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol.     

A Preliminary Study of Acute Responses to Clamped Alcohol Concentration and Family History of Alcoholism

BACKGROUND: The clamping method of alcohol administration was combined with a battery of dependent measures of frontal lobe brain function, and a novel index of acute adaptation, in a preliminary study in order to explore the paradigm's sensitivity to a familial history of alcoholism (FHA). METHODS: Ten family history-positive (FHP) and 10 family history-negative (FHN) adult social drinkers of both genders underwent alcohol clamping. Twenty minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 60+/-5 mg/dl for 150 min. Initial and adaptive responses to alcohol were assessed using scalar indices of change. One index assessed initial improvements or impairments in brain function after alcohol. The other index assessed acute adaptation (tolerance or sensitization) to alcohol while the brain's exposure to alcohol was held constant. The battery of dependent measures included subjective perceptions, neuropsychological tests, saccadic eye-movement tasks, and event-related potential (ERP) tasks. Effect sizes for FHA were estimated for 10 dependent variables that showed adequate baseline test-retest reliability (r>0.6). RESULTS: FHP subjects showed less intense initial responses to alcohol in subjective perceptions, but greater changes in the latency of volitional saccades and ERP P3 components than did the FHN controls. FHP subjects generally showed greater acute tolerance to alcohol than did controls, who showed more instances of acute sensitization at this moderate breath alcohol concentration. Effect sizes for FHA exceeded 0.4 in more than half of the indices. CONCLUSIONS: The BrAC clamping paradigm assesses initial and adaptive responses of a battery of behavioral and electrophysiological measures of frontal lobe function to ethanol that appear both reliable and sensitive to FHA.     

Essential Tremor: A Risk Factor for Alcoholism?

Four patients with essential tremor, self treated with alcohol, are reported. All had significant hepatic dysfunction. Treatment with propanolol markedly reduced the tremor and contributed to a satisfactory outcome to the alcoholism in three of the patients.