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.     

Striatal dopamine release and family history of alcoholism

BACKGROUND: The offspring of alcohol-dependent individuals are at increased risk for alcoholism. The present study was designed to determine whether mesolimbic dopamine binding potential (BP), dopamine release, stress hormones, and subjective responses to intravenous amphetamine are different in nonalcoholic offspring from families with a history of alcohol dependence [family history positive (FHP)] than in nonalcoholic offspring without a family history of alcohol dependence [family history negative (FHN)]. METHODS: Participants were 41 healthy men and women (11 FHP, 30 FHN; age range 18-29). After completing baseline psychiatric symptom and personality measures, striatal D2/D3 dopamine BP and dopamine release in response to an amphetamine challenge were measured with positron emission tomography (PET) using the D2/D3 dopamine (DA) receptor radioligand [11C]raclopride. Binding potential was defined as Bmax/KD, percent change in BP from baseline defined dopamine release. During the scans, subjects rated the degree to which they were experiencing each of 10 possible drug effects. Plasma cortisol and growth hormone (GH) were also measured at scheduled intervals during the scans. RESULTS: Neither baseline BP nor dopamine release differed by family history. Similarly, subjective responses to amphetamine did not differ by a family history of alcoholism. Although both cortisol and GH increased following administration of amphetamine, these increases did not differ between family history groups. CONCLUSIONS: Using amphetamine to provoke mesolimbic dopamine, we did not show significant differences in dopamine release, subjective responses, or stress hormone measures as a function of family history of alcoholism.     

Adrenocorticotropin Responses Following Administration of Ethanol and Ovine Corticotropin-Releasing Hormone in the Sons of Alcoholics and Control Subjects

Alcoholism is a familial disorder with both genetic and environmental determinants. The sons of alcoholic fathers have been documented to have alterations in several neuroendocrine measures. We investigated the ACTH/cortisol response to ovine corticotropin-releasing hormone (oCRH) and ethanol in men with and without a family history of alcoholism. Men were defined as family history positive (FHP) ( n = 7) if their father was alcoholic; as family history negative (FHN) ( n = 16), if their father was nonalcoholic. Ethanol (0.75 g/kg) or placebo was ingested over 15 min, 1 μg/kg oCRH was administered, and plasma ACTH/cortisol levels were determined at –20, 0, 15, 30, 60, and 90 min after oCRH. Following placebo, FHP men had lower peak ACTH response to oCRH than did FHN men (12 ± 2 vs 20 ± 2 pmol/liter, P = 0.04). In FHN men, plasma ACTH response to oCRH was blunted during the ethanol session compared to the placebo session (13 ± 1 vs 20 ± 2 pmol/liter; P = 0.006). In contrast, FHP men had similar ACTH responses to oCRH during ethanol and placebo sessions. Cortisol responses to oCRH were similar in both groups during both sessions. In summary, FHP and FHN nonalcoholic men had different plasma ACTH responses following the administration of oCRH.     

Alcohol and Secobarbital Effects as a Function of Familial Alcoholism: Extended Intoxication and Increased Withdrawal Effects

Response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism. If this is so, the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol. We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes. The data reported here are based on an extended data collection period of 3 to 18 hr postingestion, following completion of the acute laboratory portion of the study. Specifically, in the present study, dose-effect timecourse functions for a variety of physiological (heart rate, blood pressure, and breath alcohol level), subjective (analog mood, drug effect, and withdrawal, Subjective High Assessment Scale (SHAS], and psychomotor measures (Digit Symbol Substitution Test and numeric recall) were examined in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg daily) and ethanol (1 g/kg daily). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Self-reported subjective perception of intoxication reflects family history of alcoholism when breath alcohol levels are constant

BACKGROUND: The premise of this study is that the increased familial risk for alcoholism is associated with genetic determinants of the response to alcohol, characterized by sensitivity and adaptation. Following a single administration, sensitivity is the initial response to alcohol, expressed as the change in dependent measures from baseline. Adaptation of dependent measures within a single exposure to alcohol can be expressed as acute tolerance (recovery of dependent measures toward baseline values) or sensitization (movement of dependent measure further away from baseline values). This study tested the hypothesis that family history-positive (FHP) subjects are more sensitive and more adaptive to alcohol compared with family history-negative (FHN) subjects. METHODS: The initial response and development of adaptation to alcohol were assessed by using self-reported subjective perceptions during a breath alcohol concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the Sensation Scale and a visual analog scale of intoxication were acquired at baseline, after the BrAC clamp was established, and after maintenance of the clamp for 105 min. RESULTS: FHP subjects were more sensitive to alcohol compared with FHNs, as evidenced by greater changes in feelings of intoxication when the BrAC clamp was initially achieved. While the clamp was maintained, the FHP subjects adapted to the effects of alcohol and their perceptions of intoxication became indistinguishable from those of the FHN subjects. The FHP subjects had developed acute tolerance to alcohol, whereas the FHN subjects did not. Other self-reported perceptions of alcohol's effects did not distinguish between the groups. CONCLUSIONS: A differential family history of alcoholism was reflected in self-reported subjective perceptions of intoxication when the brain's exposure to a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP subjects reported greater intoxication after alcohol and subsequently developed acute tolerance to alcohol compared with FHN subjects.     

Family history of alcoholism in males: absence of distinguishing features for treatment matching

One variable for subtyping the alcoholic population that could influence treatment-matching efforts is family history of alcoholism. This study compared two groups of male patients undergoing rehabilitation for alcohol dependence (39 family history positive [FHP] versus 36 family history negative [FHN]) on a number of salient dimensions for which specific targeted intervention components might be implemented. The FHP were similar to FHN subjects on all variables except that FHP had significantly fewer years of education than did FHN. Several possible explanations to account for these findings are discussed.     

Alcohol and Secobarbital Effects as a Function of Familial Alcoholism: Acute Psychophysiological Effects

Previous research has demonstrated response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism. These response differences are thought to reflect differences in vulnerability to dependence on alcohol. Thus, the role of positive family alcoholism history in increasing risk of addiction to a variety of drug classes might be studied by determining whether FHP subjects show different responses to drug classes other than alcohol. This was done in the present study by determining dose-effect functions for a variety of physiological (heart rate, skin conductance, skin temperature), subjective (analog mood and drug effect, Subjective High Assessment Scale), and psychomotor measures (hand tremor, body sway, Digit Symbol Substitution Test, eye-hand coordination, and numeric recall) in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg by mouth) and ethanol (1 g/kg). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. At equivalent blood alcohol levels family-history positive subjects reported greater effects of ethanol than did family-history negative subjects on almost all subjective measures. Following the high dose of secobarbital, FHP but not FHN subjects showed elevated subjective effects; these effects were substantially less and were evident in fewer measures than following ethanol. In contrast to effects on the subjective measures, ethanol and secobarbital produced comparable impairment in both groups of subjects for most psychomotor responses. Group differences were not obtained on any physiological measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diazepam Preference in Males with and without an Alcoholic First-Degree Relative

The relationship between family history of alcoholism and risk for benzodiazepine abuse was examined by assessing the reinforcing and subjective effects of diazepam (DZ; 4-28 mg) in 14 normal (i.e., nonalcoholic) males with a first-degree alcoholic relative (family history positive; FHP) and in 13 control subjects without alcoholic relatives (FHN). Reinforcing effects were measured using a double-blind preference procedure in which subjects first sampled DZ and placebo (PL) and then chose the substance they preferred. Subjects were also allowed to select the dose of drug they preferred on each choice session. The subjective effects of DZ were assessed using standardized self-report questionnaires. Neither group chose the DZ more often than PL. The FHP group chose DZ slightly (but not significantly) more often than the FHN group (mean choices FHP 1.42 vs. FHN 1.15 out of 3 choice options), and they chose slightly (but not significantly) more doses of DZ within sessions (FHP 25 mg vs. FHN 18 mg). The groups did not differ in their responses to DZ on other measures (e.g., subjective drug effects or drug liking). To the extent that laboratory procedures such as the one used here provide a model for assessing the abuse liability of drugs, these results do not provide strong evidence that males with a family history of alcoholism have an elevated risk for developing benzodiazepine abuse or dependence.     

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.     

Healthy subjects with a family history of alcoholism show increased stimulative subjective effects of alcohol

Background: Research has shown that subjects with a family history positive (FHP) of alcoholism are at increased risk for alcoholism and that this group reacts differently to alcohol than family history negative (FHN) subjects. These different levels of sensitivity may make FHP persons more likely to consume alcohol. Here, we tested the hypothesis that subjects FHP for type 1 alcoholism (according to Cloninger) are more sensitive than control subjects to the stimulative, properties of alcohol following a single moderate dose of alcohol. Methods: Fifty‐one healthy men and women (22 FHP and 29 FHN) participated in 2 laboratory sessions, in which they consumed a beverage containing ethanol (0.6 g/kg in juice) or placebo (juice alone) in a randomized order. Primary dependent measures were self‐report questionnaires of mood states. Results: Subjects with family history of type 1 alcoholism showed increased stimulative responses and an elevated positive mood state after ethanol compared to controls. Conclusions: At this moderate dose, ethanol increased stimulative subjective responses in individuals who were “family history positive.” This enhanced sensitivity could motivate to exaggerated drinking and thereby increase the risk for developing alcoholism.     

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.     

The effect of naloxone on ATCH and beta-endorphin in patients with Cushing's disease

Endogenous opiates may be important in the control of ACTH secretion in men. The effect of opiate receptor blockade by naloxone on ACTH, beta-endorphin-like substance and cortisol release was studied in healthy women and in 9 patients with Cushing's disease. In the healthy subjects, ACTH, beta-endorphin and cortisol levels were increased in response to naloxone. However, in 3 our of the 9 patients with Cushing's disease, a paradoxical decrease in serum ACTH, cortisol and beta-endorphin concentrations was observed after naloxone administration. In the patients with a paradoxical response to naloxone, transsphenoidal microadenomectomy was ineffective.     

Thyrotropin and Prolactin Responses to Thyrotropin-Releasing Hormone in Young Men at High or Low Risk for Alcoholism

A reduced thyrotropin (TSH) response to TSH-releasing hormone (TRH) has been reported in a portion of abstinent alcoholic men without evidence of cirrhosis of the liver. It is not known whether this neuroendocrine change is a precursor of alcoholism or a sequelae of heavy alcohol consumption. Three of four published studies have found evidence for differences in TRH-induced TSH response in subjects at high risk for alcoholism, based on family history, compared with subjects at low risk for alcoholism. To test further the hypothesis that the TRH-induced TSH response is a vulnerability marker for alcoholism, we tested 25 young men with an alcoholic father [family history-positive (FHP)] and matched them, on alcohol consumption, to 25 young men with no identified first- or second-degree relatives with alcoholism [family history-negative (FHN)]. FHP subjects were further categorized based on whether their father had shown signs of alcohol problems before age 25 years (FHP-Early, n = 10) or after age 24 years (FHP-Late, n = 12). FHP subjects did not differ from FHN subjects in their baseline levels of thyroid hormones, glucose, Cortisol, or TSH. However, the distribution of TSH responses in the FHP subjects was skewed toward lower values, compared with FHN subjects ( p = 0.12). Furthermore, FHP-Late subjects had lower TSH responses than FHN subjects ( p = 0.02), whereas the TSH response of FHP-Early subjects was not different from FHN subjects. Prolactin responses to TRH were similar across all groups. These findings support the hypothesis that the TRH-induced TSH response may be a marker of vulnerability to alcoholism and suggest an association between the marker and risk for late-onset alcoholism.     

Ethanol and pain sensitivity: effects in healthy subjects using an acute pain paradigm

Background: The primary objective of this study was to determine whether healthy subjects without a history of heavy alcohol use or a family history of alcoholism exhibit a concentration‐dependent analgesic effect of ethanol. In a preliminary fashion, we also compared this sample to a group of subjects with a strong positive family history for alcoholism (FHP) to test the secondary hypothesis that FHP individuals will be more sensitive to the analgesic effects of alcohol compared to healthy subjects who are negative for a family history of alcoholism (FHN). Methods: Forty‐one healthy FHN subjects and 19 FHP subjects participated. Test days included an ethanol high concentration (breathalyzer = 0.100 g/dl), ethanol low concentration (breathalyzer = 0.040 g/dl) or placebo. The infusion of ethanol was via computerized pump to achieve a steady‐state (“clamp”) ethanol concentration. Noxious electrical stimulation and pain assessments were performed prior to start of placebo/ethanol infusion and at the 60‐min infusion mark. The applied current was progressively increased until the pain was reported as 5 or higher on an 11‐point Verbal Numeric Scale (VNS). Outcome variables included measures of pain threshold and tolerance and Visual Analog Scales of mood states. Results: Among FHN subjects there was a significant ethanol concentration effect on pain tolerance (F = 3.0, p = 0.05). The average change in pain stimuli required to reach a VNS of 5 or greater were (?2.4, ?1.0, and 2.2 mAmps respectively) for high concentration, low concentration, and placebo. There were no ethanol concentration related differences in pain threshold. The analgesic effect of ethanol was not correlated with changes in mood states, suggesting an independent analgesic effect of the drug. A comparison of FHP to FHN subjects produced no differences on pain responses. Conclusion: The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol’s analgesic effects.     

Risky decision-making: an FMRI study of youth at high risk for alcoholism

Background: Adolescents with a family history of alcoholism (FHP) are at risk for developing an alcohol use disorder (AUD), and some studies indicate that FHP individuals show deficits in executive functioning. The ability to make adaptive decisions is one aspect of successful executive functioning that is often measured during risk‐taking tasks; however, this behavior has not been examined in FHP youth. As impaired decision‐making could predispose FHP youth to make poor choices related to alcohol use, the current study examined the neural substrates of risk‐taking in FHP adolescents and their family history negative (FHN) peers. Methods: Thirty‐one (18 FHP, 13 FHN) youth between 13 and 15 years old were included in this study. All youth had used little to no alcohol prior to study involvement. Functional magnetic resonance imaging was used to examine the neural substrates of risk‐taking during the Wheel of Fortune (WOF) decision‐making task ( Ernst et al., 2004 ) in FHP and FHN youth. Results: FHP youth did not differ from FHN youth in risk‐taking behavior, but showed less brain response during risky decision‐making in right dorsolateral prefrontal cortex and right cerebellar regions compared with FHN peers. Conclusions: Despite no behavioral differences on the WOF decision‐making task, FHP youth exhibited atypical neural response during risk‐taking compared with FHN peers. Atypical brain activity, in regions implicated in executive functioning could lead to reduced cognitive control, which may result in risky choices regarding alcohol use. This could help explain the higher rates of AUDs seen in FHP adolescents. Further examination of risky behavior and associated brain response over the course of adolescence is necessary to characterize the vulnerabilities of FHP youth in the absence of alcohol abuse.     

Effects of naloxone on adrenal cortex regulation in patients with primary aldosteronism

Excess production of proopiomelanocortin (POMC)-derived peptides with aldosterone-stimulating activity has been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To further investigate this issue, the opiate receptor antagonist naloxone was administered to 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. Clinical and hormonal effects of iv administration of naloxone (10 mg as a bolus) were compared with those obtained in 8 normal subjects. In normals as well as in APA and IHA patients, naloxone caused a significant increase in plasma cortisol, and no change in ACTH, plasma renin activity (PRA) and aldosterone levels. All subjects were retested after 2 mg dexamethasone. ACTH and cortisol were reduced and PRA was unchanged in all groups, without modifications after naloxone. Baseline aldosterone showed no significant changes in all groups. While normal subjects and APA failed to show any aldosterone response to naloxone after dexamethasone, IHA patients demonstrated a significant decrease. beta-endorphin concentrations were in the normal range before and after dexamethasone. In conclusion, naloxone may have a direct action upon adrenal zona fasciculata increasing the cortisol responsiveness to physiological levels of ACTH in either normals or APA and IHA patients. The decrease of aldosterone induced by naloxone in IHA may be due to an intraadrenal opioid control of zona glomerulosa in this disorder.     

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.     

Family history of alcohol use disorders and neuromaturation: a functional connectivity study with adolescents

Abstract

Background: A positive family history (FHP) of alcohol use disorders (AUD) is linked to increased risk for personal AUD, but the mechanisms behind this risk are unclear. Previous research suggests that a subtle neurodevelopmental lag in FHP adolescents may contribute to risk for future AUD. Methods: Functional magnetic resonance imaging (fMRI) response to a spatial working memory (SWM) task was examined for markers of neuromaturational delay in 85 youth with and without FHP. It was hypothesized that FHP adolescents (n?=?24, ages 12–14 years), as compared to matched FHN youth (n?=?26, ages 12–14 years), would show less similarity to brain connectivity observed in older adolescents (n?=?35, ages 16–20 years) and that statistical comparison of SWM functional connectivity models would differentiate FHN and FHP youth. Structural equation modeling tested the fit of brain response connectivity between FH groups and against the older-adolescent model. Results: Patterns of connectivity were more similar between older adolescent and FHN than FHP adolescents; FHP youth demonstrated higher association between right posterior and left frontal brain regions than FHN and older adolescent youth. Comparison of FH groups indicated a significant difference on the pathway from the right superior parietal lobule to the left middle frontal gyrus. Conclusions: These findings provide additional support for the notion of a neuromaturational lag in FHP youth. Protracted neuromaturation may be a mechanism by which FH increases risk for alcohol dependence, and this less mature neural connectivity pattern may provide a novel endophenotype for identifying youth at risk for drinking problems.     

Event-related Brain Potentials in Individuals at High and Low Risk for Developing Alcoholism: Failure to Replicate

Event-related brain potentials (ERPs) were used to compare young men having a positive paternal family history for alcoholism (FHP) with carefully matched control subjects having no family history for alcoholism (FHN). The P300 ERP component was obtained from all subjects (n = 10/group) with a complex auditory paradigm before and on two occasions after they received a placebo drink which they were told might contain alcohol. The procedures employed replicated those of a previous study in which FHP subjects showed diminished P300 potentials compared to FHN subjects under the placebo as well as ethanol consumption conditions--a finding which raised the possibility that the P300 ERP component might be a biological marker for subjects at high risk to develop alcoholism. No differences between the family history groups were obtained for the P300 or any other ERP component using the replication procedures. Both groups demonstrated a decrease in P300 amplitude across trial blocks in a similar fashion suggesting that habituation effects may have diminished the ERP response.     

Family history of alcoholism and psychiatric co-morbidity in Brazilian male alcoholics and controls

The present study was aimed at replicating, in a sample of Brazilian subjects, findings generated mostly in developed countries on the relative prevalence of alcohol problems, associated psychiatric disorders, family history of alcoholism and other familial psychiatric disorders in alcoholics and controls. A group of Brazilian male alcoholics (n =103) and controls (n =63) at first admission to ambulatory or inpatient treatment were interviewed individually using sections of the Structured Clinical Interview for DSM-III-R. Information on demographic characteristics, alcohol-related problems, psychiatric problems and family history of alcoholism and depression were collected from all subjects. Alcoholics had a higher prevalence of a family history of alcoholism, a family history of depression and of a personal history of other psychiatric disorders when compared to controls. Comparisons between FHP and FHN alcoholics, although preliminary, showed few significant differences between these subgroups. Comparisons between FHP and FHN controls showed a non-significant trend towards a higher prevalence of psychiatric problems and towards antisocial behaviours among those with a positive family history of alcoholism. The findings point to the importance of cross-cultural studies on genetic and environmental factors related to alcohol dependence.