Preference for higher sucrose concentrations in cocaine abusing-dependent patients

BACKGROUND: Animal studies suggest that preference for relatively high concentrations of sweet solutions and lack of control over sweet solution consumption is related to a preference for alcohol over water. There also is evidence in humans that alcoholics prefer high concentration sweet solutions. This study was designed to determine whether patients with cocaine use disorder also prefer high concentrations of sweet solutions. METHODS: Sixteen patients with cocaine abuse/dependency were compared with 16 inpatient controls with an affective disorder as to their preferences for increasing concentrations of sucrose solutions. Patients were administered aqueous sucrose solutions ranging from 0.05 to 0.83 M. They were then asked to rate their degree of preference for, and the degree of sweetness of each solution. RESULTS: Cocaine abusing/dependent patients significantly more often preferred the highest sucrose concentration (0.83 M). CONCLUSIONS: The above information suggests that cocaine abusing/dependent patients, like alcoholics, and in contrast to inpatient controls, share a preference for high concentrations of sucrose.     

A case-comparison study of executive functions in alcohol-dependent adults with maternal history of alcoholism

IntroductionAs executive dysfunctions frequently accompany alcohol dependence, we suggest that reports of executive dysfunction in alcoholics are actually due, in some case to a maternal history of alcohol misuse (MHA+). A history of maternal alcohol dependence increases the risk for prenatal alcohol exposure to unborn children. These exposures likely contribute to executive dysfunction in adult alcoholics. To assess this problem, we propose a case-comparison study of alcohol-dependent subjects with and without a MHA.MethodsTen alcohol-dependent subjects, with a maternal history of alcoholism (MHA) and paternal history of alcoholism (PHA), were matched with 10 alcohol-dependent people with only a paternal history of alcoholism (PHA). Executive functions (cancellation, Stroop, and trail-making A and B tests) and the presence of a history of three mental disorders (attention deficit hyperactivity disorder, violent behavior while intoxicated, and suicidal behavior) were evaluated in both populations.ResultsAlcohol-dependent subjects with MHA showed a significant alteration in executive functions and significantly more disorders related to these functions than PHA subjects. The major measures of executive functioning deficit are duration on task accomplishment in all tests. Rates of ADHD and suicidality were found to be higher in MHA patients compared to the controls.ConclusionA history of MHA, because of the high risk of PAE (in spite of the potential confounding factors such as environment) must be scrupulously documented when evaluating mental and cognitive disorders in a general population of alcoholics to ensure a better identification of these disorders. It would be helpful to replicate the study with more subjects.     

Species differences in polysaccharide and sugar taste preferences

This study compared the polysaccharide and sugar taste preferences of humans and four rodent species (laboratory rats, Rattus norvegicus; Golden Syrian hamsters, Mesocricetus auratus; Mongolian gerbils, Meriones unguiculatus; Egyptian spiny mice, Acomys cahirinus). In Experiment 1 human subjects rated the pleasantness, sweetness, and flavor intensity of polysaccharide (Polycose), sucrose, and maltose solutions at concentrations of 0.0125 M to 0.4 M, and 1% to 32% concentrations. At the higher molar concentrations Polycose was rated as less sweet and less pleasant than the sucrose and maltose solutions; there were no differences in the flavor intensity ratings. With the percent concentrations Polycose was rated as less sweet and less flavorable as the sucrose and maltose solutions; there were no reliable differences in the pleasantness ratings. In Experiment 2, the Polycose, sucrose, and maltose preferences of rats, hamsters, gerbils, and spiny mice were compared using 24 hr two-bottle tests (saccharide vs. water) at concentrations of 0.001 M, 0.005 M, 0.01 M, and 0.1 M. In general, the rats displayed stronger preferences for Polycose and maltose than did the other three species. In addition, the gerbils showed a stronger Polycose preference at the 0.1 M concentration than did the hamsters and spiny mice, and the spiny mice display a weaker preference for sucrose than did the other three species. Within species comparisons revealed that all four species displayed preferences for Polycose that were as strong or stronger than their preferences for sucrose and maltose. With only a few exceptions, male and female rodents did not differ in their saccharide preferences. Thus, while rats show the most robust Polycose preference of the four rodent species, all four species were attracted to the taste of polysaccharides. Humans, on the other hand, reported that Polycose solutions were unpleasant. The results suggest that rodents have taste receptors for starch-derived polysaccharides that humans lack.     

Interhemispheric electroencephalographic coherence as a biological marker in alcoholism

Electroencephalographic coherence scores in 21 teetotaler first-degree relatives of alcoholics, 27 subjects with alcohol dependence and 21 healthy subjects without a family history of alcohol abuse were compared. The relatives had significantly higher coherence scores in the frontal and parietal leads than the alcoholics and in the frontal and centroparietal leads than in the healthy subjects. This might represent a trait marker of resilience in subjects at high risk for the development of alcoholism.     

Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism.

OBJECTIVE: A deficit in serotonergic neurotransmission has been linked to impulsive behavior, as well as to disorders characterized by disinhibition. The present study tested the hypothesis that young men at high risk for alcoholism demonstrate greater behavioral disinhibition after acute dietary depletion of tryptophan, the amino acid precursor of serotonin. METHOD: A double-blind, placebo-comparison, between-subjects study design was used. Nonalcoholic young men with a multigenerational paternal family history of alcoholism (N = 13) or with no family history of alcoholism (N = 15) in two previous generations were administered mixtures of tryptophan-deficient amino acid to achieve plasma tryptophan depletion. Comparison subjects with a multigenerational paternal family history of alcoholism (N = 1) and comparison subjects with no family history of alcoholism (N = 18) were given a balanced mixture. Five hours after this, all were tested on a modified Taylor task and a go/ no-go task measuring aggressive response and disinhibition, respectively. RESULTS: Plasma tryptophan levels were reduced by 89% in both groups. Tryptophan depletion had no effect on aggressive response. In contrast, tryptophan-depleted individuals with a family history of alcoholism made more commission errors (responses to stimuli associated with punishment or loss of reward) than did tryptophan-depleted individuals with no family history of alcoholism and those receiving the balanced (comparison) mixture of amino acid in either group. CONCLUSIONS: Low serotonin levels may be implicated in the high disinhibition or impulsivity observed in some individuals with a genetic vulnerability to alcohol abuse or dependence.     

Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of alcoholism.

BACKGROUND: Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk for alcoholism, we examined the effects of naloxone, an opioid antagonist, on corticotropin and cortisol responses in nonalcoholic subjects differentiated by paternal history of alcoholism. METHODS: Placebo-controlled, balanced, within-subject design involving 2 test days over a period of 3 to 7 days. Thirty-six subjects (67% male; 53% paternal-history-positive; mean age = 25.0 years) were screened to exclude substance abuse or dependence. Subjects received intravenous naloxone 125 microg/kg or placebo, with sessions in random order. Plasma corticotropin and cortisol were measured for up to 120 min post infusion. RESULTS: Corticotropin responses at baseline and following naloxone did not differ by paternal history of alcoholism; however, paternal-history-positive subjects exhibited greater cortisol concentrations at baseline, and at 15 and 30 min after naloxone administration. Paternal-history-positive subjects also had an earlier and greater peak cortisol response to naloxone and a nonsignificant trend for a greater area under the cortisol time curve than paternal-history-negative subjects. CONCLUSIONS: These findings suggest that individuals with greater vulnerability to alcoholism may have altered Hypothalamic-pituitary axis (HPA) dynamics, a finding that is consistent with a growing body of data on the role of opioidergic neurotransmission in the inherited risk of alcoholism.     

The social complications of chronic alcohol abuse: relative influence of family history and severity of alcohol dependence

Alcoholics with a family history of the disease are said to present more severe consequences than alcoholics without such a history. This study examined the frequency distribution of severe alcohol dependence and police arrests for public drunkenness across samples of alcoholics with (n = 77) and without (n = 37) a family history of alcoholism. Both the percentage of subjects presenting severe dependence and the history of police arrests were greater in the positive family history group, but these differences did not reach conventional levels of statistical significance. However, results of logistic regression analyses demonstrate that male sex, younger age and, above all, severity of alcohol dependence, are better correlates of the occurrence of police arrests than is the subject's family history of alcoholism. The picture presented by this sample of outpatient alcoholics appears to qualify some currently held assumptions of the influence of family history on the phenomenology of alcoholism.     

Middle-latency auditory evoked potentials in children at high risk for alcoholism.

PURPOSE: In the course of a high-risk study for alcoholism, the middle-latency auditory evoked potentials (MAEPs) of children of alcoholics were explored. MATERIAL AND METHODS: A series of auditory clicks (0.1 ms, 60 dB SL, 1.1/s) were used to record the Pa and Pb peaks of the MAEPs in 15 children of alcoholics with a multigenerational family history of alcoholism, and 17 control subjects, ranging from 10 to 14 years of age. RESULTS: The latency of Pb was shorter in the high-risk than in the control group, and there was also a significant risk group by age interaction on Pa latency. The amplitude of Pa was smaller in the children of alcoholics. CONCLUSIONS: The characteristics of the MAEPs of the high-risk subjects did not match the pattern of abnormalities previously observed in chronic alcoholics, which are supposed to be a consequence of the neurotoxic effects of ethanol. Nonetheless, the results showed significant differences in MAEPs between children of alcoholics and controls, pointing to an anomalous pattern of information transmission from thalamus to cortex that should be further analyzed using larger samples in a broader age range.     

Biological markers in alcoholism

The search for biological markers of a predisposition towards alcoholism is the result of data indicating that this disorder is genetically influenced. The present paper reviews some methodological considerations important for trait marker research in alcoholism. To date, the most promising results have come from studies comparing populations at elevated risk (i.e., sons of alcoholics) to controls. Such investigations point towards a decreased intensity of reaction to ethanol in sons of alcoholics, a decreased amplitude of the P300 wave of event-related potentials, and the possibility of a unique pattern of waves on the background cortical EEGs. The potential implication of these findings is discussed.     

Arginine vasopressin and adrenocorticotropin secretion in response to psychosocial stress is attenuated by ethanol in sons of alcohol-dependent fathers

Familial risk and environmental stress promote the development of alcohol dependence. We investigated whether a positive family history of alcoholism affects the neuroendocrine response to a standardized laboratory stress test in healthy subjects without alcohol use disorders. Twenty-four high-risk subjects with a paternal history of alcoholism (PHA) and 16 family history negative (FHN) controls were evaluated. Psychosocial stress was induced by having subjects deliver a 5-min speech and mental arithmetics in front of an audience on separate days, after drinking either placebo or ethanol (0.6 g/kg) in a randomized sequence. Adrenocorticotropin (ACTH) was measured in 10 plasma samples covering up to 75 min after the stress test. Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and at 75 min after stress onset. The stress test induced a phasic increase in ACTH secretion. At the time of maximum ACTH, AVP was significantly increased in relation to baseline. Compared to placebo, alcohol administration significantly attenuated maximum ACTH concentration in PHA but not FHN subjects, and decreased AVP measured in the same samples in PHA but not FHN subjects. We conclude that activation of the hypothalamic-pituitary-adrenal system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. Secretion of both ACTH and AVP suggest that alcohol attenuates the stress response selectively in PHA but not FHN subjects. This might imply some short-term positive alcohol effect in sons of alcoholics, but also constitute a mechanism by which their risk to develop alcohol use disorders is increased.     

Behavioural and emotional problems in children of alcoholic mothers and fathers

 The Child Behavior Check List (CBCL) was used to compare a sample of 103 Danish children of alcoholics (CoA) to a Danish population-based sample (N = 780). The CoA had a significantly greater incidence of symptoms on 17 of the 118 CBCL items. Compared to the reference population, daughters of alcoholics were more impaired than sons of alcoholics on most CBCL measures. In families with maternal alcoholism daughters had higher internalising and depression scores than sons, and in families with paternal alcoholism, sons had higher internalising and depression scores than daughters. The CoA also had a significantly greater risk of scoring above the 95th percentile on internalising behaviour, depression symptoms and socially deviant behaviour. On all CBCL dimensions, almost half of the CoA samples functioned as well as the average of the reference population. The results from this study suggest that CoA should be regarded as a risk group but with very heterogeneous consequences in response to parental alcoholism. Accepted: 29 November 1999     

Parental alcoholism as a risk factor in benzodiazepine abuse: a pilot study

Nine of 12 men with a family history of alcoholism but only two of 12 control subjects had euphoric responses to alprazolam. The authors conclude that sons of alcoholics may be at high risk to abuse alprazolam.     

High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors

CONTEXT: Predisposition to alcoholism is likely an interaction between genetic and environmental factors that confer vulnerability and protection. Alcoholic subjects have low levels of dopamine D(2) receptors in striatum, and increasing D(2) receptor levels in laboratory animals reduces alcohol consumption. OBJECTIVES: To test whether high levels of D(2) receptors may be protective against alcoholism and whether this is mediated by their modulation of activity in orbitofrontal cortex and cingulate gyrus (regions involved in salience attribution, emotional reactivity, and inhibitory control). DESIGN: Research (nonalcoholic subjects with a family history of alcoholism) and comparison (nonalcoholic subjects with a negative family history) sample. SETTING: Outpatient setting. PARTICIPANTS: Fifteen nonalcoholic subjects who had an alcoholic father and at least 2 other first- or second-degree relatives who were alcoholics (family-positive group) and 16 nonalcoholic controls with no family history of alcoholism (family-negative group). MAIN OUTCOME MEASURES: Results of positron emission tomography with raclopride C 11 to assess D(2) receptors and with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain function). Personality measures were obtained with the Multidimensional Personality Questionnaire. RESULTS: Availability of D(2) receptors was significantly higher in caudate and ventral striatum in family-positive than family-negative subjects. In family-positive but not family-negative subjects, striatal D(2) receptors were associated with metabolism in anterior cingulate (Brodmann area 24/25) and orbitofrontal (Brodmann area 11) and prefrontal (Brodmann area 9/10) cortices, and with personality scores of positive emotionality. CONCLUSIONS: The higher-than-normal D(2) receptor availability in nonalcoholic members of alcoholic families supports the hypothesis that high levels of D(2) receptors may protect against alcoholism. The significant associations between D(2) receptors and metabolism in frontal regions involved with emotional reactivity and executive control suggest that high levels of D(2) receptors could protect against alcoholism by regulating circuits involved in inhibiting behavioral responses and in controlling emotions.     

Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are associated with alcoholism-related traits.

BACKGROUND: This study examined the hypothesis that allelic variants of the ionotropic glutamatergic N-methyl-D-aspartate receptor (NMDAR) are associated with vulnerability to alcoholism and some related traits. METHODS: We investigated the silent G2108A and C2664T polymorphisms of the NMDAR1 and the NMDAR2B genes, respectively. The case control study included 367 alcoholic and 335 control subjects of German origin. The family-based study comprised 81 Polish alcoholic patients and their parents using the transmission disequilibrium test. RESULTS: The genotype frequencies of the NMDAR1 polymorphism differed significantly between control and alcoholic subjects. This difference was also observed in more homogenous subgroups of alcoholic subjects with vegetative withdrawal syndrome and Cloninger type 1. Patients with a history of delirium tremens or seizures during withdrawal showed a significantly increased prevalence of the A allele. Genotyping of the NMDAR2B polymorphism revealed a significantly reduced T allele in Cloninger type 2 alcoholics and in patients reporting an early onset compared with control subjects. Our family-based study for NMDAR2B, revealed a trend to a preferred transmission of the C allele by the fathers, and families with early-onset patients contributed most to this trend. CONCLUSIONS: These results suggest that variants in NMDAR genes are associated with alcoholism and related traits.     

Norepinephrine transporter gene polymorphism is not associated with susceptibility to alcohol dependence

Abnormalities in monoamine neurotransmission have been implicated in the pathogenesis of alcoholism, mood disorders and schizophrenia. Murine norepinephrine transporter gene (NET) has been mapped to a region on chromosome 8 where a quantitative trait locus for ethanol sensitivity. Therefore we tested whether norepinephrine transporter (NET) gene variants confer susceptibility to either alcohol dependence or severe alcohol withdrawal symptoms. There is a highly polymorphic silent G1287A mutation in the NET gene. In our study 157 alcoholics and 185 healthy unrelated matched control subjects were analyzed for a silent G1287A mutation. No significant differences in allele and genotype distribution between control subjects f(A)=0.33 and alcoholics f(A)=0.29 were found. No significant results were found in more homogenous subgroups, i.e. alcoholics with severe alcohol withdrawal (seizures, delirium), early onset age<26 nor dependent patients with positive familial history of alcoholism. These results suggest that the NET gene polymorphism in exon 9 accession number: mRNA: NM_001043, genomic contig.: NT_019610, is unlikely to be involved in the susceptibility to alcoholism and severe alcohol withdrawal.     

Influence of premorbid risk factors on neuropsychological performance in alcoholics

This report provides new evidence that neuromedical risk factors influence levels of behavioral impairment in alcoholics. Using a factorial model, the effects of age, neuromedical risk history, and duration of sobriety were studied in relation to neuropsychological performance. The data showed a consistent interaction between duration of abstinence and risk status: Recently detoxified alcoholics (sober 1 month) with a positive premorbid risk history had worse neuropsychological performance than did those without such historical risk events. By contrast, long-term abstinent alcoholics (sober 4 years) did not demonstrate the interaction between alcohol history and positive premorbid risk history. The present results are held to mean that neuromedical risk factors may exert a differential influence on test scores of recently detoxified men, suggesting a source of variance in neurobehavioral studies of alcoholism requiring attention by investigators.     

Platelet MAO activity as a biological marker in subgroups of alcoholism

In the Stockholm Adoption Study, two types of alcoholism, "Type I" and "Type II", have been identified on the basis of genetic predisposition. In the present study, this classification has been applied to a clinical sample. The two types of alcoholism were clinically clearly identifiable. Type I alcoholism was characterized by late onset and few social complications. Type II alcoholism was characterized by early onset, use and abuse not only of alcohol, but also of glue, cannabis, amphetamine and opioids, together with several social complications. The subjects with Type II alcoholism had also more alcoholism and depression among their first-degree relatives than the subjects with Type I alcoholism. Furthermore, the two types of alcoholism were separable by means of the biological marker - platelet MAO activity. While platelet MAO activity was normal in Type I alcoholics, as compared with healthy controls, it was clearly low in the Type II alcoholics. This subclassification of alcoholism seems to be of value in future studies concerning the etiology, epidemiology and treatment of alcoholism.     

Ethylmaltol Odor Enhances Salivary Hemodynamic Responses to Sucrose Taste as Detected by Near-Infrared Spectroscopy

The perceived intensity of the taste of a food is enhanced only if the odor of the food is perceptually similar to the taste. For example, a caramel-like odor enhances the perceived intensity of sweetness. The way gustatory and olfactory signals are integrated in the brain depends largely on one’s previous experiences with taste and odor pairings. To elucidate the effects of a sweet, sugary odor, ethylmaltol, on sucrose taste, as perceived by the central integration of flavor, we recorded salivary hemodynamic responses to the odor and taste pairings using near-infrared spectroscopy (NIRS) of seven panelists. First, we observed concentration-dependent increases in the amplitude of the responses to 0 to 6 % sucrose solutions. Second, when ethylmaltol odor was added to a 4 % sucrose solution, we observed a significant increase in the amplitude of the responses from all panelists. The addition of ethylmaltol to a tasteless solution caused no significant change in the amplitude of the salivary hemodynamic response. These results indicate that the sweet odor of ethylmaltol enhances the salivary hemodynamic response when combined with a sweet taste. Therefore, a congruent combination of sweet odor and taste greatly enhances salivary responses, which are dependent on the central integration of odor and taste.     

Spatial-anatomical mapping of NoGo-P3 in the offspring of alcoholics: evidence of cognitive and neural disinhibition as a risk for alcoholism.

OBJECTIVE: The concept of disinhibition as a behavioral and biological trait has been considered to be involved in the etiology of alcoholism and its co-existing disorders. The magnitude and functional mapping of event-related potential P3(00) components were analyzed, in order to examine the possible response inhibition deficits in the offspring of alcoholics. METHODS: The P3 components were compared between 50 offspring of alcoholics (OA) and a matched normal control group (NC) using a visual Go/NoGo task. The low-resolution electromagnetic tomography (LORETA) was used to analyze the functional brain mapping between groups. RESULTS: The results indicated that the OA group manifested decreased P3 amplitude during the NoGo but not the Go condition compared to the NC group. The voxel-by-voxel analysis in LORETA showed group differences at several brain regions including prefrontal areas during the processing of NoGo but not Go signals. CONCLUSIONS: The decreased NoGo-P3 suggests that cognitive and neural disinhibition in offspring of alcoholics may serve as a neurocognitive index for a phenotypic marker in the development of alcoholism and related disorders. SIGNIFICANCE: Dysfunctional neural and response inhibition in the offspring of alcoholics perhaps provides an endophenotypic marker of risk for the development of alcoholism and related disorders.     

Influence of premorbid risk factors on neuropsychological performance in alcoholics

Abstract

This report provides new evidence that neuromedical risk factors influence levels of behavioral impairment in alcoholics. Using a factorial model, the effects of age, neuromedical risk history, and duration of sobriety were studied in relation to neuropsychological performance. The data showed a consistent interaction between duration of abstinence and risk status: Recently detoxified alcoholics (sober 1 month) with a positive premorbid risk history had worse neuropsychological performance than did those without such historical risk events. By contrast, longterm abstinent alcoholics (sober 4 years) did not demonstrate the interaction between alcohol history and positive premorbid risk history. The present results are held to mean that neuromedical risk factors may exert a differential influence on test scores of recently detoxified men, suggesting a source of variance in neurobehavioral studies of alcoholism requiring attention by investigators.