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.     

Impact of habitual cocaine smoking on the physiologic response to maximum exercise

BACKGROUND: Habitual smoking of alkaloidal cocaine (crack) has been reported to be associated with a number of cardiopulmonary complications that may not be clinically obvious but could potentially interfere with normal physiologic responses to exercise and thus impair maximum exercise performance. STUDY OBJECTIVE: To evaluate the impact of regular use of cocaine on maximum exercise. DESIGN: Observational study in crack users and age- and gender-matched control subjects. SUBJECTS: Thirty-five habitual cocaine smokers (21 male and 14 female) and 29 age-matched sedentary control nonsmokers of cocaine (15 male and 14 female), all of whom were in good general health. METHODS: In these subjects, we compared physiologic responses to symptom-limited, incremental maximal exercise performed on a cycle ergometer using a ramp protocol. Comparisons were made for men and women separately. RESULTS: For both men and women, long-term cocaine smokers had a reduced aerobic capacity (maximum oxygen consumption) compared with control nonsmokers but did not show evidence of ventilatory limitation, reduced gas exchange threshold, increased physiologic dead space, or gas exchange abnormality at maximum exercise compared with the healthy control subjects. Although cocaine smokers had reduced maximum heart rates compared with control subjects, the relationship between submaximal heart rate and oxygen uptake was normal, indicating a normal cardiovascular response pattern. However, effort perception was similar between the two groups despite the difference in heart rate at maximum exercise, suggesting the possibility of perceptual dysfunction for effort. Differences in aerobic capacity between the crack users and nonusers could not be explained by differences in physical fitness or altered perception of dyspnea. CONCLUSION: In the subjects we studied, long-term cocaine smoking was associated with reduced maximum exercise performance, probably due to poor motivation or altered effort perception. No other identifiable physiologic abnormality appeared to limit exercise in the habitual crack users.     

Alcoholism and psychological differentiation: Effect of alcohol on field dependence.

1st of a series of studies of stability of perceptual field dependence (taken as an indicator of level of differentiation) during the alcoholic cycle. These studies are in preparation for a longitudinal study of the development of alcoholism. In this 1st study, alcohol ingestion failed to have a significant effect on performance in 2 tests of field dependence, the rod-and-frame and body-adjustment tests. In a 3rd test, the embedded-figures test, speed of locating a simple figure in a complex design was reduced under the influence of alcohol, but this change seems attributable to reduced ability to concentrate under alcohol rather than to a change in perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Histopathologic and molecular alterations in bronchial epithelium in habitual smokers of marijuana, cocaine, and/or tobacco

BACKGROUND: Tobacco smoking has been observed to cause molecular alterations in bronchial epithelium that antedate the development of lung carcinoma. The rising prevalence of marijuana and cocaine use among young adults in the United States prompted us to investigate whether similar molecular and histopathologic alterations occur in habitual smokers of marijuana and/or cocaine who may or may not also smoke tobacco. METHODS: Bronchoscopy was performed in 104 healthy volunteer subjects, including 28 nonsmokers and 76 smokers of one or more of the following substances: marijuana, tobacco, and/or cocaine. Bronchial mucosa biopsy specimens and brushings were analyzed for histopathologic changes, for immunohistopathologic expression of intermediate or surrogate end-point markers that are linked to an increased risk of cancer (Ki-67 [a marker of cell proliferation], epidermal growth factor receptor, p53, Her-2/neu [also known as erbB-2 and ERBB2], globular actin, and abnormal DNA ploidy). Reported P values are two-sided. RESULTS: Smokers of any one substance or of two or more substances exhibited more alterations than nonsmokers in five to nine of the 10 histopathologic parameters investigated (all P < .05), and they exhibited more molecular abnormalities than nonsmokers. Differences between smokers and nonsmokers were statistically significant (all P < or = .01) for Ki-67, epidermal growth factor receptor, globular actin, and DNA ploidy. There was general agreement between the presence of molecular abnormalities and histopathologic alterations; however, when disagreement occurred, the molecular abnormalities (e.g., Ki-67 and epidermal growth factor receptor) were more frequently altered (all P < or = .01). CONCLUSIONS: These findings suggest that smoking marijuana and/or cocaine, like tobacco smoking, exerts field cancerization effects on bronchial epithelium, which may place smokers of these substances at increased risk for the subsequent development of lung cancer.     

Predictive validity of cocaine, sedative, and alcohol dependence diagnoses.

This study examined the predictive validity of Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) (R. L. Spitzer et al, 1990) based substance dependence diagnoses (i.e., cocaine, sedative, and alcohol) for 518 opioid-dependent outpatients entering methadone maintenance. Patients were followed over 1 year of treatment, which involved daily methadone substitution supplemented by individual and group counseling. Urine specimens were tested randomly 1–4 times per month. Patients diagnosed with current cocaine, sedative, or alcohol dependence were more likely to use these drugs than were patients with past only or no dependence syndrome. Current cocaine dependence predicted early treatment dropout. The results demonstrate the predictive and discriminant validity of several substance dependence diagnoses common among patients in substance abuse or other psychiatric treatment settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biochemical markers of alcohol use and abuse: experiences from the Pilot Study of the WHO/ISBRA Collaborative Project on state and trait markers of alcohol. International Society for Biomedical Research on Alcoholism

The effects of acute ethanol and acetaldehyde treatment on cell proliferation, cell adhesion capacity, neutral red incorporation into lysosomes, glutathione content, protein sulfhydryl compounds, lipid peroxidation, inner mitochondrial membrane integrity (MTT test), lactate dehydrogenase activity (LDH) and ultrastructural alterations were investigated in a human fetal hepatic cell line (WRL-68 cells). WRL-68 cells were used, due to the fact that, although this cell line expresses some hepatic characteristics, it does not express alcohol dehydrogenase or cytochrome P450 activity, so it could be a good model to study the effect of the toxic agents per se. Cells were exposed during 120 min with 200 mM ethanol or 10 mM acetaldehyde. Under these conditions, cells presented 100% viability and no morphological alteration was observed by light microscopy. Acetaldehyde-treated cells reduced their proliferative capacity drastically while the ethanol-treated ones presented no difference with control cells. Cell adhesion to substrate, measured as time required to adhere to the substrate and time required to detach from the substrate, was diminished in acetaldehyde WRL-68-treated cells. Cytotoxicity measures as neutral red and MTT test showed that acetaldehyde-treated cells presented more damage than ethanol-treated ones. Cellular respiratory capacity was compromised by acetaldehyde treatment due to 40% less oxygen consumption than control cells. Lipid peroxidation values, measured as malondialdehyde production, were higher in ethanol-treated WRL-68 cells (127%) than in acetaldehyde-treated ones (60%) to control cell values. Lactate dehydrogenase activity (LDH) in extracellular media of ethanol-treated cells presented the highest values. GSH content was reduced 95% and thiol protein content was diminished severely in acetaldehyde-treated cells. Transmission electron microscopy showed more ultrastructural alterations in cells treated with acetaldehyde. The results indicate that acetaldehyde, like ethanol, produced damage at cellular level, although more damage could be observed in acetaldehyde WRL-68-treated cells.     

Alcoholism and alcohol abuse among women: report of the Council on Scientific Affairs. American Medical Association

We describe characteristics of women alcohol abusers, risk factors for alcoholism in women, barriers to treatment, and implications and strategies for physicians dealing with alcohol abuse in women patients, including risk assessments and intervention strategies. Alcohol abuse and alcoholism have a different physiologic effect on women than on men. Societal attitudes about women and alcohol and internal (self-perception) and external (environmental) factors can create barriers to the detection and treatment of female alcohol abusers. Physicians are in an excellent position to address the medical, psychologic, and social concomitants of alcoholism and alcohol abuse. The Council on Scientific Affairs recommends that physicians become more active in the prevention, diagnosis, and treatment of alcohol-related problems in women, including the diseases that may be associated with chronic alcohol abuse and the effect of alcohol on the developing fetus. Specific American Medical Association policy and recommendations for physician practice are included.     

Validating a five-factor marijuana motives measure: Relations with use, problems, and alcohol motives.

This study adapted and extended M. L. Cooper's (1994) Drinking Motives Measure to examine marijuana motives among 299 college students. An exploratory factor analysis supported the hypothesized 5-factor marijuana motives model, resulting in enhancement, conformity, expansion, coping, and social motives. Analyses supported the internal consistency and concurrent validity of the 5 marijuana motives. Marijuana motives were significant predictors of marijuana use and added to the prediction of use-related problems above and beyond the contribution of lifetime use. Motives and gender interacted in predicting use and use-related problems. Parallel regression analyses revealed that marijuana and alcohol motives predicted comparable amounts of variance in use and use-related problems. However, different patterns of relations emerged across drugs, supporting the discriminant validity of the marijuana and alcohol motives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of depressive symptoms on smoking abstinence and treatment adherence among smokers with a history of alcohol dependence.

This study examined the effect of depressive symptoms on smoking abstinence and treatment adherence among smokers with a past history of alcohol dependence. Participants (24 women, 27 men) were randomly assigned to behavioral counseling (BC) or behavioral counseling plus cognitive-behavioral mood management training (CBT). The Hamilton -Rating Scale for Depression (HRSD; A Hamilton, 1967) was administered to assess baseline depressive symptoms. Participants who received CBT and had higher HRSD scores were more likely to achieve short-term abstinence from smoking and attend more treatment sessions than those with lower depression scores, whereas for BC participants the effect of HRSD scores was the opposite. Smokers with a history of alcohol dependence reporting high levels of depressive symptoms may benefit from a mood management intervention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Progression from a smoking lapse to relapse: Prediction from abstinence violation effects, nicotine dependence, and lapse characteristics.

Determinants of progression from an initial smoking lapse to relapse, using prospective data from 133 participants were examined. Participants used palm-top computers to record their first lapse, and their reaction to it, within minutes of the event, and were followed for 3 months to assess subsequent smoking. Indicators of the Abstinence Violation Effect—self-efficacy, attributions, and affective reactions to the lapse—generally failed to predict progression to relapse, but participants who felt like giving up after the first lapse progressed more rapidly to a second lapse. Participants who attempted restorative coping were less likely to progress to another lapse on the same day. Those whose lapses were triggered by stress progressed more quickly, whereas those triggered by eating and drinking or accompanied by alcohol consumption progressed more slowly. More nicotine-dependent participants progressed more rapidly toward relapse, but neither the amount smoked in the first lapse nor its subjective reinforcement predicted progression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relations among personality, symptoms of alcohol and marijuana abuse, and symptoms of comorbid psychopathology: Results from a community sample.

This study examined the relation of the Five-Factor Model (FFM) of personality to symptoms of alcohol and marijuana abuse before and after controlling for symptoms of antisocial personality disorder (APD) and internalizing psychopathology. The 481 participants completed a well-validated measure of the FFM and a structured diagnostic interview at age 21 years. Hierarchical regression analyses indicated that unique constellations of personality characteristics were associated with symptoms of alcohol abuse, marijuana abuse, APD, and internalizing disorders. For example, symptoms of alcohol abuse were associated with high Extraversion and low Conscientiousness, whereas symptoms of marijuana abuse were characterized by low Extraversion and high Openness to Experience. Findings have implications for models of the etiology and treatment of substance use and abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland

A population-based, case-control study of pancreas cancer was undertaken in Opole, Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer: this is the first aetiological study of pancreas cancer reported from Poland where the reported mortality rate has doubled since 1963. This study of pancreas cancer has provided some further supporting evidence of an association between increased pancreas risk with increasing levels of cigarette smoking. The risk rose with increasing lifetime cigarette consumption with a trend which was weakly significant (p = 0.061). Findings regarding lifetime tea and coffee consumption were not consistent with intake of either beverage increasing the risk of this disease. There was a strongly significant trend of decreasing risk with increasing lifetime consumption of tea (p < 0.001), which was also apparent when the analysis was restricted to subjects who were interviewed directly. For coffee consumption, which is low in Poland, there was also a negative association apparent in the data which was not statistically significant among the sub-set of subjects who were directly interviewed. The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p = 0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland.     

Risk factors for adolescent substance abuse and dependence: Data from a national sample.

A national household probability sample of 4,023 adolescents aged 12 to 17 years was interviewed by telephone about substance use, victimization experiences, familial substance use, and posttraumatic reactions to identify risk factors for Diagnostic and Statistical Manual of Mental Disorders- (4th ed.; American Psychiatric Association, 1994) defined substance abuse/dependence. Age and ethnicity data were available for 3,907 participants. Major findings were (a) adolescents who had been physically assaulted, who had been sexually assaulted, who had witnessed violence, or who had family members with alcohol or drug use problems had increased risk for current substance abuse/dependence; (b) posttraumatic stress disorder independently increased risk of marijuana and hard drug abuse/dependence; and (c) when effects of other variables were controlled, African Americans, but not Hispanics or Native Americans, were at approximately 1/3 the risk of substance abuse/dependence as Caucasians. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of monetary contingencies on smoking relapse: Influences of trait depression, personality, and habitual nicotine intake.

Of 56 male smokers, 34 were randomly assigned (by 60% random odds) to quit smoking immediately, whereas the remaining 22 were assigned to quit after an additional 31 days. Compensation ($300) was contingent on abstinence for a minimum of 31 or 2 days (depending on random assignment) and completion of all experimental sessions. Contingencies for the immediate-quit group required 31 days of abstinence; those for the delayed-quit group required only 2 days of abstinence. Contingency duration (31 vs. 2 days) predicted days to relapse. All but 4 of the 31-day contingency participants maintained abstinence for at least 31 days, whereas only 3 of the 2-day contingency group abstained for 31+ days. However, 31-day contingencies did not result in longer postcontingency time to relapse. Higher trait neuroticism, depression, and psychopathic deviate scores predicted decreased time to relapse. Prequit cotinine concentrations and Fagerstr?m Tolerance Questionnaire scores failed to predict time to relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence

The Tap (taxis toward peptides) receptor and the periplasmic dipeptide-binding protein (DBP) of Escherichia coli together mediate chemotactic responses to dipeptides. Tap is a low-abundance receptor. It is present in 5- to 10-fold-fewer copies than high-abundance receptors like Tar and Tsr. Cells expressing Tap as the sole receptor, even from a multicopy plasmid at 5- to 10-fold-overexpressed levels, do not generate sufficient clockwise (CW) signal to tumble and thus swim exclusively smoothly (run). To study the signaling properties of Tap in detail, we constructed reciprocal hybrids between Tap and Tar fused in the linker region between the periplasmic and cytoplasmic domains. The Tapr hybrid senses dipeptides and is a good CW-signal generator, whereas the Tarp hybrid senses aspartate but is a poor CW-signal generator. Thus, the poor CW signaling of Tap is a property of its cytoplasmic domain. Eighteen residues at the carboxyl terminus of high-abundance receptors, including the NWETF sequence that binds the CheR methylesterase, are missing in Tap. The Tart protein, created by removing these 18 residues from Tar, has diminished CW-signaling ability. The Tapl protein, made by adding the last 18 residues of Tar to the carboxyl terminus of Tap, also does not support CW flagellar rotation. However, Tart and Tapl cross-react well with antibody directed against the conserved cytoplasmic region of Tsr, whereas Tap does not cross-react with this antibody. Tap does cross-react, however, with antibody directed against the low-abundance chemoreceptor Trg. The hybrid, truncated, and extended receptors exhibit various levels of methylation. However, Tar and Tapl, which contain a consensus CheR-binding motif (NWETF) at their carboxyl termini, exhibit the highest basal levels of methylation, as expected. We conclude that no simple correlation exists between the abundance of a receptor, its methylation level, and its CW-signaling ability.     

Mood states and sleepiness in college students: influences of age, sex, habitual sleep, and substance use

Survey and laboratory evidence suggests several factors affecting sleep-wake patterns of college students. These factors include social and academic demands, diminution of parental guidance, reduction of total sleep time, delayed bedtime, and increased nap episodes. In this study, we examined the problem of falling asleep in school as a correlate of negative moods in this population (N = 294). A multivariate analysis showed significant main effects of sleepiness on mood states based on the Profile of Mood States. Students who fell asleep in school reported higher negative mood states. Significant interactions were observed among sleepiness and age, sex, race, and duration of sleep. Specifically, younger men reported higher negative moods. No interactions were noted for alcohol and marijuana consumption; however, students who fell asleep in school consumed more alcoholic beverages and smoked more than those who did not. Perhaps falling asleep in school could be used as an index that characterizes students who manifest adaptive or psychological difficulty.     

Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: Basic findings from the National Comorbidity Survey.

Studying prevalence of Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) drug dependence among Americans 15–54 yrs old, the authors found about 1 in 4 (24%) had a history of tobacco dependence; about 1 in 7 (14%) had a history of alcohol dependence, and about 1 in 13 (7.5%) had a history of dependence on an inhalant or controlled drug. About one third of tobacco smokers had developed tobacco dependence and about 15% of drinkers had become alcohol dependent. Among users of the other drugs, about 15% had become dependent. Many more Americans age 15–54 have been affected by dependence on psychoactive substances than by other psychiatric disturbances now accorded a higher priority in mental health service delivery systems, prevention, and sponsored research programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.