Platelet Monoamine Oxidase Activity in Alcoholics, Alcoholics with Drug Dependence, and Cocaine Addicts

The main objective of this investigation was to study the influence of drug dependence on platelet monoamine oxidase (MAO) activity in the presence and absence of alcoholism. One hundred and thirteen admissions to alcohol and drug treatment facilities participated in the study. Twenty-six met the criteria for alcoholism (group I), seventy-eight subjects were alcohol-/cocaine- and cannabis-dependent (group II), and the remaining nine were patients with DSM-III-R diagnosis of cocaine addiction (group III). MAO activity was assayed radiochemically with [¹⁴C]tyramine as a substrate (221 μM). The results of this study showed that platelet MAO activity [nmol of product formed x (mg protein)⁻¹ x hr⁻¹] (mean ± SE) was significantly ( p < 0.01) lower in all of these subjects (group 1, 5.50 ± 0.80; group II, 3.90 ± 0.50; group III, 4.3 ± 1.60) as compared with controls (14.85 ± 1.13). Measurements of platelet MAO activity may provide us with a reliable biochemical marker for alcoholism and perhaps addiction to other substances of abuse (i.e., cocaine).     

The Density of Monoamine Oxidase B Sites Is Not Altered in the Postmortem Brain of Alcoholics

The status of the enzyme monoamine oxidase B (MAO-B) was directly evaluated in the postmortem brain from 20 alcoholics and 23 matched controls. The density of MAO-B sites was quantified by the specific binding of the selective inhibitor [³H]Ro 19-6327 (lazabemide) (8 nM) to cortical membranes. A positive correlation between age at death and MAO-B density was observed in the total sample ( r = 0.37, p = 0.015). The density of MAO-B in alcoholics (B_max= 1,263 ± 131 fmol/mg of protein) was not different form that in control (B_max= 1,131 ± 96 fmol/mg of protein). Ethanol in vitro inhibited [³H]Ro 19-6327 binding, with similar potency in membranes form alcoholics ( K _i= 280 ± 13 mM) and controls ( K _i= 338 ± 84 mM). The present results in brain tissue contrast with previous reports of decreased MAO-B enzymatic activity in platelets of alcoholics, but strongly agree with recent genetic studies on MAO-B status in alcoholism.     

A Genetic Familial Study of Monoamine Oxidase B Activity and Concentration in Alcoholics

Platelet monoamine oxidase B (MAO B) activity and concentration were studied in a small sample of alcoholic families ( n = 8) and in 20 unrelated, nonalcoholic controls. Complex segregation analyses of familial data indicated that both activity and concentration are controlled by a single major gene locus with a multifactorial background effect accounting for 0–50% of the variance. When the alcoholic family members ( n = 24) were compared with the controls, all determinations of activity display significant differences, whereas MAO B concentration levels showed no difference. These results indicated that the lowered MAO B activities frequently reported among alcoholics do not reflect a change in the number of MAO B macromolecules expressed in platelets, but could be caused by the presence of an inhibitor or by a polymorphic or variant form of the enzyme.     

Brain GABA-Transaminase and Monoamine Oxidase After Chronic Ethanol Treatment in Rats

The activities of γ-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO-A and -B) were estimated in various brain regions of rats exposed to ethanol for 90 weeks. During the first period (weeks 1–58), the rats had access to both ethanol (10% w/v) and water during a 24-hr interval at the end of each week. At this point, the animals were given either a saline injection (intraperito-neally, group 1) or an ethanol injection (2.0 g/kg ip, group 2). During the second period (weeks 59–90), the rats in groups 1 and 2 had continuous access to both ethanol and water. The third group was composed of untreated control rats. Compared with controls, there was an increase of 20–45% in the mean brain GABA-T activity in both groups of ethanol-treated rats. However, analysis of the data for the individual ethanol-treated rats revealed a considerable difference in brain GABA-T activity. Thus, -30% of the ethanol-treated rats showed approximately twice the activity of rats in the exposed groups and in the control group. There was no connection between ethanol intake, water intake, or body weight and GABA-T activity in any of the brain regions examined. There was no effect of ethanol in vitro on the activity of GABA-T in the brain cortex in concentrations of 20–100 mki, whereas acetaldehyde inhibited the activity by 15% at these concentrations. The present results suggest that there is a bimodal distribution with respect to the effect of ethanol on rat brain GABA-T activity. With regard to MAO, the activities (both forms) in the brain remained unaffected after 90 weeks of ethanol treatment.     

Platelet Monoamine Oxidase Activity in Subgroups of Alcoholics and Controls: Results from the Collaborative Study on the Genetics of Alcoholism

Objective : Platelet monoamine oxidase (MAO) B activity levels were evaluated to determine whether low platelet MAO activity is a marker for alcoholism, correlates of alcoholism (e.g., cigarette smoking), or a subtype of alcoholism. Methods : Adult women ( n = 788) and men ( n = 685) participating in the Collaborative Study on the Genetics of Alcoholism study were evaluated with a semistructured interview, and blood samples were obtained for determination of platelet MAO activity using tryptamine (0.1 mM) as substrate. DSM-III-R alcohol-dependent individuals were subgrouped using four currently available methods (e.g., two variations of the type 1/type 2 scheme, primary versus secondary typology, type A/type B dichotomy). Results : In the overall sample, subjects'gender, cigarette smoking status, and the Collaborative Study on the Genetics of Alcoholism site at which their platelets were prepared explained 22% of the variance in platelet MAO activity levels, and multivariate analysis showed that carrying a broad diagnosis of alcohol dependence did not uniquely explain any additional variance in platelet MAO activity levels. Furthermore, within each of the alcoholic subgrouping methods tested, there were no significant differences in platelet MAO activity for type 1 versus type 2, type A versus type B, or primary versus secondary alcoholics. Conclusions : Cigarette smoking and male gender are associated with decreased platelet MAO activity levels. After considering these factors, a diagnosis of alcohol dependence does not predict any additional variance in MAO-B activity. Phenotypes of alcoholics (e.g., type 1 versus type 2, type A versus type B, primary versus secondary) do not differ in platelet MAO activity. The results suggest that decreased platelet MAO activity is not a trait marker of alcoholism or one of its subtypes; but, rather, is a state marker of cigarette smoking.     

Low Platelet Gamma-Aminobutyrate Aminotransferase and Monoamine Oxidase Activities in Chronic Alcoholic Patients

The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) were estimated in blood platelets from 25 male chronic alcoholics and from 27 healthy male volunteers without histories of alcohol abuse. Based on clinical criteria, the alcoholics were classified into type 1 or type 2 alcoholism. The activity of GABA-T was found to be lower both in type 1 and type 2 alcoholics than in healthy volunteers. With regard to MAO, the platelet activity was found to be significantly lower only in type 2 alcoholics in concordance with previous reports. No significant correlation was found between the activities of GABA-T and MAO in the blood platelets of healthy volunteers. The inhibitory effect of 400 mM ethanol on the platelet MAO activity increased with decreasing concentrations of the substrate phenylethylamine. The degree of inhibition of ethanol on the platelet MAO activity, however, did not differ significantly between alcoholics and controls.     

Personality Characteristics of Sisters and Spouses of Male Alcoholics

Sisters of alcoholics from high-density multigenerational families were assessed to determine personality characteristics. Spousal similarity was evaluated in proband/spouse pairs and in spouse pairs from the parental generation, allowing for comparisons of selection versus contagion as explanations for this similarity.
Sisters were found to differ from control women with respect to Alienation and Social Closeness from the Multidimensional Personality Questionnaire, and Scale 6 (Paranoia) from the Minnesota Multiphasic Personality Inventory. Only spouses from the parental generation were similar on Alienation, suggesting that exposure over time (contagion) leads to greater similarity in parents from High-Risk families. Modest correlations in spouse pairs from both generations suggest that assortative mating for Social Closeness occurs among the parents of these individuals from High-Risk families, and further suggest that a diminished level of Social Closeness for sisters of alcoholics may be mediated in part by additive genetic variance. It is concluded that assortative mating for particular traits may contribute to increased risk for alcoholism. Also, failure to mate assortatively for other traits (e.g., Traditionalism, Harm Avoidance) may also contribute to increased rates in High-Risk families.     

Circulating Monoamine Oxidase B and Phenolsulfotransferase Activities in Essential Hypertensive Patients

Circulating monoamine oxidase (MAO) and phenolsulfotransferase M and P (PST M, PST P) activities were determined in 24 untreated essential hypertensive patients and in 35 age-matched normotehsive healthy controls. These enzymes are involved in the inactivation of monoamines and their metabolites. After lysis of blood, enzymatic activities were determined by radioenzymatic techniques using as substrates [¹⁴C]-beta-phenylethylamine for MAO, 3–methoxy-4–hydroxyphenylglycol for PST M and phenol for PST P. MAO activity measured by this method is fully accounted for by platelet MAO B activity. Women presented higher MAO activity than men. Significantly lower MAO-B activities were     

Tridimensional Personality Traits in Sons of Alcoholic and Nonalcoholic Fathers

Sons of alcoholics (SOAs; n = 27) and sons of nonalcoholics (SONAs; n = 23) were compared across Tridimensional Personality Questionnaire (TPQ) and Sensation Seeking scales and measures of plasma homovanillic acid and platelet monoamine oxidase activity. SOAs and SONAs did not differ significantly on any measure. The pattern of correlations between TPQ and Sensation Seeking scales provided some support for the construct validity of TPQ measures. Scores on the TPQ Novelty Seeking scale and platelet monoamine oxidase activity were significantly inversely associated ( r =–0.52, p < 0.02) among SOAs, but not among SONAs ( r =–0.06).     

胃起搏对大鼠胃窦肌间神经丛单胺氧化酶mRNA表达的影响

目的研究胃窦肌间神经丛中单胺氧化酶mRNA表达,探讨5羟色胺(5-HT)在胃起搏机制中的作用。方法通过手术建立Wistar大鼠胃起搏模型(近远端胃各缝制一对电极),分为起搏组(n=10)和对照组(n=6)。采用逆转录聚合酶链反应(RT-PCR)检测起搏组和对照组胃窦肌间神经丛中MAO-A mRNA、MAO-B mRNA的表达量,以恒定表达的β-actin作为内参照。计算MAO-AmRNA、MAO-B mRNA与β-actin mRNA表达积分光密度值的比例(MA/B,MB/B),以反映组织中MAO-AmRNA、MAO-B mRNA的相对表达量。结果RT-PCR研究显示起搏组MAO-A mRNA表达显著弱于对照组,起搏组MA/B比值明显较对照组较少(0.37±0.11vs0.95±0.57,P<0.001);而起搏组MAO-B mRNA表达与对照组无差别,两组间MB/B比值比较也无显著性意义(0.97±0.24vs1.01±0.58,P>0.05)。结论胃起博后胃肌间神经丛内单胺氧化酶mRNA表达量明显减少,表明胃窦肌间神经丛内5-HT可能在胃起搏中发生了重要作用。     

Effect of the Cytochrome P-1450IIE1 Genotype on Ethanol Elimination Rate in Alcoholics and Control Subjects

We studied an influence of genetic polymorphisms in the cytochrome P-450IIE1 (CYP2E1) gene on ethanol elimination rate in alcoholic patients and healthy subjects. The CYP2E1 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method for 124 alcoholics and 54 healthy subjects. There was no significant difference in the gene frequency of CYP2E1 between alcoholics and healthy control subjects. Blood ethanol concentrations in the 65 alcoholics on admission ranged from 0.32 to 4.22 mg/ml. In the patients with the c1/c2 genotype, the elimination rate was significantly correlated with blood ethanol concentration. In each of the three genotypes of CYP2E1, the patients were divided into three groups based on ethanol concentrations. The average of the ethanol elimination rate in the patients with c1/c2 having blood ethanol levels of ≧2.5 mg/ml was significantly higher than the rates in the two other groups of c1/c2. When blood ethanol levels were ≧2.5 mg/ml, the elimination rate in the patients with c1/c2 was significantly higher than that in those with c1/cl. Regardless of the CYP2E1 genotype, the elimination rate in the alcoholics was higher than that in the control subjects when blood ethanol levels were < 1.0 mg/ml. These results suggest the possibility that the c2 allele of CYP2E1 influences the rate of ethanol elimination at high ethanol levels. The rate of ethanol elimination was independent of liver disorder judged by serum total bilirubin values.     

Gendered Members of Alcoholics Anonymous: Varieties of Spiritual Experiences in Recovery

Women and men share similar as well as different strategies in developing their spirituality as part of their overall 12-Step experience. Special attention is paid to gender differences to account for a variety of spiritual experiences in recovery. The language and use of metaphors as women and men work the 12 Steps in achieving a “spiritual awakening” is explored, recognizing the predominantly male ethos of Alcoholics Anonymous since its inception. The influence of age in expressions of spirituality, distinguishing between young adults, middle-age adults, and older adults, is referenced. Need for further understanding of gender differences, with a focus on the spiritual dimensions of recovery, is recommended.     

Glatt's Curve Revisited: A Pilot Study Investigating the Progression of Recovery in Alcoholics Anonymous

Glatt's 1958 curve is used in AA to illustrate the nature of alcohol dependence and recovery, and spiritual gains are considered an important point in the recovery progression. Sixteen AA members, who had experienced transformational changes, were interviewed regarding the progression of recovery surrounding their transformation. Their progressions were compared with Glatt's hypothetical curve. For most, the transformation was located in the middle of the recovery progression and was positively correlated with Glatt's progression. For this sample, the working of the 4th step of AA appeared to be an important catalyst for transformational change. In addition, the experience of transformation often resulted in a rebirth of ideals and a new set of enduring moral values.     

Pathways into Risk: Temperament and Behavior Problems in Three- to Five-Year-Old Sons of Alcoholics

Evidence suggests that a child with a difficult temperament, reared in an alcoholic family, is at high risk for the development of behavior problems that antedate the emergence of antisocial behavior, alcoholism, and coactive psychopathology. However, the causal linkage between difficult temperament and problem behavior in childhood, and antisociality and alcohol abuse in adulthood is far from certain, in part because few studies assess emergent behavior patterns in young children of alcoholics. In this study, we investigated the temperament-behavior problem relationship in 191 3- to 5-year-old boys, 149 of whom were being reared in high-risk alcoholic, low socioeconomic environments. Boys were classified as high in problem behavior or not based on standardized clinical cut-off scores for Total Behavior Problems from the Child Behavior Checklist. Results indicated that boys rated in the clinical range for total behavior problems exhibited more characteristics of difficult temperament than boys who were not rated in the clinical range. Parents of the boys in the clinical group had significantly more alcohol-related problems, higher levels of antisociality, and significantly lower levels of socioeconomic status, income, and education. Results are consistent with the supposition that the difficult temperament-behavior problem relationship flourishes in the context of an antisocial, alcoholic family environment.     

Humility and 12-Step Recovery: A Prolegomenon for the Empirical Investigation of a Cardinal Virtue in Alcoholics Anonymous

Alcoholics Anonymous (AA) offers a live stage to study how humility is worn by thousands for another day of sobriety and more freedom from the bondage of self. It has been the coauthors’ intent to emphasize the significance of humility as a cardinal virtue across the 12-Step program and as essential to all its key elements. The coauthors have placed this emphasis in the context of a wider theological history of thought as this converged on Bill W. and AA. In addition, the coauthors have offered a constructive developmental interpretation of the 12 Steps that relies on a model of four modulations of humility. Finally, the coauthors have reviewed in brief some approaches to the measurement of humility in this context, and suggest several aims for future research.     

Upregulation of Serotonin Transporter by Alcohol in Human Dendritic Cells: Possible Implication in Neuroimmune Deregulation

Background: Alcohol is the most widely abused substance and its chronic consumption causes neurobehavioral disorders. It has been shown that alcohol affects the function of immune cells. Dendritic cells (DC) serve as the first line of defense against infections and are known to accumulate neurotransmitters such as 5‐hydroxytryptamine (5‐HT). The enzyme monoamine oxidase‐A (MAO‐A) degrades 5‐HT that is associated with clinical depression and other neurological disorders. 5‐HT is selectively transported into neurons through the serotonin transporter (SERT), which is a member of the sodium‐ and chloride‐dependent neurotransmitter transporter (SLC6) family. SERT also serves as a receptor for psychostimulant recreational drugs. It has been demonstrated that several drugs of abuse such as amphetamine and cocaine inhibit the SERT expression; however, the role of alcohol is yet to be elucidated. We hypothesize that alcohol can modulate SERT and MAO‐A expression in DC, leading to reciprocal downregulation of 5‐HT in extracellular medium. Methods: Dendritic cells were treated with different concentrations (0.05% to 0.2%v/v) of alcohol for 24–72 hours and processed for SERT and MAO‐A expression using Q‐PCR and Western blots analysis. In addition, SERT function in DC treated with alcohol both in the presence and absence of imipramine, a SERT inhibitor was measured using 4‐[4‐(dimethylamino)styryl]‐1‐methylpyridinium iodide uptake assay. 5‐HT levels in culture supernatant and intracellular 5‐hydroxy indole acetic acid (5‐HIAA) and cyclic AMP were also quantitated using ELISA. Results: Dendritic cells treated with 0.1% alcohol for 24 hours showed significant upregulation of SERT and MAO‐A expression compared with untreated DC. We also observed that 0.1% alcohol enhanced the function of SERT and decreased extracellular 5‐HT levels compared with untreated DC cultures, and this was associated with the elevation of intracellular 5‐HIAA and cyclic AMP levels. Conclusions: Our study suggests that alcohol upregulates SERT and MAO‐A by elevating cyclic AMP, which may lead to decreased concentration of 5‐HT in the extracellular medium. As 5‐HT is a major neurotransmitter and an inflammatory mediator, its alcohol‐mediated depletion may cause both neurological and immunological deregulation.     

Alcohol Schema Acquisition in Preschoolers: Differences Between Children of Alcoholics and Children of Nonalcoholics

Cognitive schemas provide the structure within which children organize their knowledge and beliefs about the use of alcohol. The development of schemas about alcohol should be affected both by age and parental patterns of alcohol use. We examined differences in alcohol schema development among 139 male children of alcoholics (COAs) and 82 controls [children of nonalcoholics (NCOAs)] utilizing the Appropriate Beverage Task as an indicator of these processes. Overall, the vast majority of the sample identified at least one alcoholic beverage from photographs, even at age 3. COAs were more likely to identify at least one alcoholic beverage. With age controlled, COAs were better able to identify specific alcoholic beverages and correctly identified a larger number of alcoholic beverages. There was a trend for these children of alcoholic men to attribute more alcoholic beverage use to male adults than NCOAs. Moreover, differences in these children's attributions of alcoholic consummatory behavior were predicted by their parents' current consumption levels. Results provide evidence that alcohol schemas are detectable in early childhood and are more common in children from alcoholic homes. Discussion focuses on the potential relevance of these risk attributes to the development of more fully formed alcohol expectancies and to the later emergence of alcohol-related difficulty.     

Formation of malondialdehyde adducts in livers of rats exposed to ethanol: role in ethanol-mediated inhibition of cytochrome c oxidase

BACKGROUND: Previous studies in our laboratory demonstrated that short-term ethanol consumption by maternal rats increased the hepatic levels of 4-hydroxynonenal (HNE) in both the adult and the fetus. Additionally, HNE inhibited cytochrome c oxidase (COX) by forming adducts with the enzyme subunits. The present study examined modification of COX by another major aldehydic lipid peroxidation product, malondialdehyde (MDA), and its role in COX inhibition by ethanol. METHODS AND RESULTS: It is demonstrated in vitro that MDA inhibits the activity of purified COX while forming adducts with the enzyme. Compared with HNE, MDA is a more potent inhibitor of COX. Overnight incubation at room temperature caused an 80% decrease in COX activity by MDA versus a 67% decrease by HNE. MDA produced marked inhibition of COX activity at physiologically relevant concentrations, e.g., 43% inhibition at 10 microM. Although our previous studies documented that HNE formed adducts primarily with subunit IV of COX via histidine residues, the current report showed that MDA forms adducts with both subunit IV and subunit V via lysine residues. Furthermore, both aldehydes induce carbonyl formation in subunit IV. The in vivo role of MDA in the impairment of COX by ethanol is assessed in both adult and fetal liver after maternal ethanol consumption. CONCLUSIONS: The results showed that: (1) there are significant increases in MDA levels in liver homogenate as well as mitochondria in both adult and fetal livers after ethanol exposure; (2) these MDA levels are in the nanomole/mg protein range, in contrast to picomole/mg protein range of HNE in identical setting; and (3) ethanol-induced production of MDA is accompanied by enhanced formation of MDA adducts with COX. These findings suggest that MDA may play at least as equally an important role as HNE in ethanol-induced inhibition of COX.