Factor and simplex models for repeated Measures: Application to two psychomotor measures of alcohol sensitivity in twins

As part of a larger study, data on arithmetic computation and motor coordination were obtained from 206 twin pairs. The twins were measured once before and three times after ingesting a standard dose of alcohol. Previous analyses ignored the time-series structure of these data. Here we illustrate the application of simplex models for the genetic analysis of covariance structures in a repeated-measures design and compare the results with factor models for the two psychomotor measures. We then present a bivariate analysis incorporating simplex processes common and specific to the two measures. Our analyses confirm the notion that there is genetic variation affecting psychomotor performance which is switched on in the presence of alcohol. We compare the merits of analysis of mean products versus covariance matrices and confront some practical problems that may arise in situations where the number of subjects is relatively small and where the causal structure among the latent variables places a heavy demand on the data.This work was aided by NATO Grant 86/0823 and grants from the Belgian National Research Fund, the State University of Gent, and the Catholic University of Leuven. The authors would very much like to thank Drs. R. Derom and R. Vlietinck for making possible the Twin Data Analysis Workshop. The collection of data was supported by a grant from the Australian Associated Brewers to N. G. Martin, J. G. Oakeshott, J. B. Gibson, and G. A. Starmer.     

A twin study of psychomotor and physiological responses to an acute dose of alcohol

A battery of psychomotor tasks and physiological measures was administered to 206 pairs of twins before alcohol and then three times at hourly intervals after they ingested a standard dose of ethanol (0.75 g/kg body weight). Repeat measurements were obtained for 41 of these pairs on a second occasion. Performance on motor coordination, standing steadiness, pursuit rotor, arithmetic computation, and reaction-time tasks deteriorated after alcohol, but decrements on the five tasks were generally independent of each other. Measurements of blood pressure, pulse rate, and skin temperature were all elevated following alcohol intake, but these responses were also uncorrelated. The variance in many of these measures increased after alcohol. An analysis of covariance structure revealed that most of this additional variance exposed by alcohol was genetic in origin, particularly for standing steadiness, pursuit rotor, arithmetic computation, and pulse rate. Up to 50% of the variance in body sway after alcohol was estimated to be due to genetic factors expressed only under the influence of alcohol. Although significant correlations were found with blood alcohol concentration, previous drinking experience, and the personality trait Extraversion, little of the genetic variance exposed by alcohol could be explained by these predictors. It is concluded that the sources of the considerable genetic variation affecting performance under alcohol must be sought elsewhere.This work was supported by the Australian Associated Brewers.     

Effects of age, sex and genes on sister chromatid exchange

Sister chromatid exchange (SCE) was studied in cultured lymphocytes from a limited series of 21 like-sexed twin pairs; 11 monozygotic (MZ) and 10 dizygotic (DZ) pairs. The 18 subjects, who were between 57 and 61 years old, had an SCE mean value () of 8.0 whereas the 24 subjects between 33 and 39 years of age had a mean of 6.8. The difference was statistically significant ( P <0.001). The effect of age appeared to be present in both sexes. No significant difference was found between females (%7.3) and males (%7.5), nor between smokers (%7.3) and non-smokers (%7.4). Drug users had a slightly higher mean (%7.9) than non-users (= 7.0) ( P < 0.05). This trend was found in each age group. The within-pair variance was slightly higher in DZ than in MZ pairs. The difference was not significant. We conclude that genetic factors are probably not a major source of subject variation in SCE mean value.     

Change in cohabitation and intrapair similarity of monozygotic (MZ) cotwins for alcohol use,extraversion, and neuroticism

We have reported cross-sectional evidence that behavioral similarities of adult monozygotic (MZ) cotwins are associated with their age at initial separation and the frequency of their subsequent social interaction (Kaprioet al., 1987; Roseet al., 1988; Rose and Kaprio, 1988). Twins who separated early and twins in infrequent interaction were less alike. Data for those reports came from a 1981 survey of the Finnish Twin Cohort. The Finnish cohort had been surveyed in 1975 with a similar questionnaire, and we now report a longitudinal analysis of the 1975–1981 surveys. All cohabiting MZ cotwins, ages 18–25 at the 1975 baseline, were followed up in 1981, and pairwise similarities at baseline and follow-up were compared for three groups: MZ pairs that remained cohabiting, separated pairs in which the cotwins retained regular contact with one another, and separated cotwins whose social interactions at follow-up were infrequent. For alcohol consumption and EPI Neuroticism scores, relative similarities of the MZ cotwins at follow-up paralleled the relative frequencies of their social contact; baseline differences in resemblance for Extraversion scores preceded follow-up differences in social interaction. These findings clarify the directional nature of associations found in our cross-sectional data and provide new, more compelling evidence of effects of shared experience on sibling resemblance for some dimensions of adult behavior.     

Familial influences on heart rate, blood pressure, and self-report anxiety responses to stress: Results from 100 twin pairs

Two hundred healthy adolescent to middle-aged individuals (12–44 years, M= 20 years) were tested in a standardized stress protocol. These individuals comprised 20 monozygotic female, 20 monozygotic male, 20 samesex dizygotic female, 20 same-sex dizygotic male, and 20 opposite-sex dizygotic twin pairs. Familial influences on heart rate, blood pressure, and self-report anxiety responses to four different kinds of stressors (Visual-Verbal Test for Conceptual Thought, mental arithmetic, isometric handgrip, cold pressor) were assessed using biometrical genetic model fitting. Evidence of significant genetic effects on resting heart rate and blood pressure was obtained, providing heritability estimates of .65, .63, and .58 for resting heart rate and systolic and diastolic blood pressure, respectively. Cardiovascular reactivity to the Visual-Verbal Test, mental arithmetic, and the cold pressor test appeared to be primarily influenced by genetic and idiosyncratic (nonfamilial) environmental factors, whereas reactivity to handgrip was more related to effects of the family environment. The results of multivariate model fitting suggested that the genetic effects on reactivity were relatively independent of those affecting resting heart rate and blood pressure and that there was significant overlap of genetic influences on heart rate and blood pressure responses to the two active coping tasks.     

The interactive effects of extended wakefulness and low-dose alcohol on simulated driving and vigilance

OBJECTIVES: Sleep deprivation and alcohol both impair driving performance. This study assessed the interactive effect of low-dose alcohol and extended wakefulness. DESIGN: Repeated-measures, crossover design evaluating psychomotor and driving function in a non-sleep-deprived state and after extended wakefulness with and without low-dose alcohol. SETTING: Teaching hospital sleep laboratory. PARTICIPANTS: Nineteen volunteer professional drivers. INTERVENTION & MEASUREMENTS: Driving simulation (AusEd) and the Psychomotor Vigilance Task (PVT) were measured in a rested state (12-15 hours awake) and after extended wakefulness (18-21 hours awake) during two sessions. Alcohol was administered during one session, with performance measured at blood alcohol concentrations (BAC) of 0.00%, 0.03%, and 0.05% in a non-sleep-deprived state, and at 0.03% after extended wakefulness (at 01:00 and 03:00). During the second session, tests were performed at the same times without alcohol. RESULTS: The combination of extended wakefulness and low-dose alcohol had significant deleterious effects on reaction time and lapses (PVT) and variation in lane position and speed (AusEd). Extended wakefulness (18-21 hours awake) combined with low-dose alcohol (0.03% BAC) resulted in more lapses (t = -2.75, P < 0.05) and greater variation in lane position (t = -3.94, P < 0.01) and speed (t = -2.79, P < 0.05) than did a BAC of 0.05% in a rested state. CONCLUSION: The combination of legal low-dose alcohol and extended wakefulness results in impairment worse than that at an alcohol level known to increase accident risk. Avoiding alcohol when driving after extended wakefulness may reduce accident risk.     

Effect of alcohol on sex steroid receptor levels in the hypothalamus and pituitary of male rats

Laboratory of Physiology of the Endocrine System, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. A. Pankov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 2, pp. 204–207, February, 1989.     

The effects of social homogamy and cultural inheritance on the covariances of twins and their parents: A LISREL model

In general, models involving parent-offspring transmission are not possible to specify in LISREL due to the complex constraints implied by assortative mating and genotype-environmental correlation. In this short note we describe one simple model of resemblance among twins and their parents which can be accommodated in the LISREL specification due to the strong assumption of social homogamy. The specification is described fully and checked for identification, and its power to resolve different parameters is briefly examined.     

The effects of age and sex on mental rotation performance,verbal performance,and brain electrical activity

This study examined the effects of age and sex on mental rotation performance, verbal performance, and brain-wave activity. Thirty-two 8-year-olds (16 boys) and 32 college students (16 men) had EEG recorded at baseline and while performing four computerized tasks: a two-dimensional (2D) gingerbread man mental rotation, a 2D alphanumeric mental rotation, of three-dimensional (3D) basketball player mental rotation, and lexical decision making. Additionally, participants completed a paper- and pencil water level task and an oral verbal fluency task. On the 2D alphanumeric and 3D basketball player mental rotation tasks, men performed better than boys, but the performance of women and girls did not differ. On the water level task, men performed better than women whereas there was no difference between boys and girls. No sex differences were found on the 2D gingerbread man mental rotation, lexical decision-making, and verbal fluency tasks. EEG analyses indicated that men exhibited left posterior temporal activation during the 2D alphanumeric task and that men and boys both exhibited greater left parietal activation than women and girls during the 2D gingerbread man task. On the 3D basketball player mental rotation task, all participants exhibited greater activation of the right parietal area than the left parietal area. These data give insight into the brain activity and cognitive development changes that occur between childhood and adulthood.     

Determinants of experimental allergic responses: interactions between allergen dose, sex and age

The prevalence of allergic diseases is influenced by sex and age. Although mouse models are widely used in allergy research, few experimental studies have examined the interaction effects of sex and age on allergy outcomes. Our aim was to investigate the individual and combined effects of sex and age on allergic sensitization and inflammation in two mouse models: an intraperitoneal (i.p.) and an intranasal (i.n.) sensitization model. We also investigated how the allergen immunization dose interacted with age and sex in the i.p. model. Female and male mice were immunized i.p. or i.n. with ovalbumin when 1, 6 or 20 weeks old. In both models, allergen challenges were performed by i.n. delivery. Serum antibodies, draining lymph node cytokine release and airway inflammatory responses were assessed. In the i.p. model, the antibody and cytokine levels and airway inflammation were highly influenced by immunization dose and age. The responses increased with age when using a low immunization dose, but decreased with age when using a high immunization dose. In the i.n. model, antibody production and airway tissue inflammation increased with age. Female compared with male mice generally developed more pronounced antibody and inflammatory responses. Relative to older mice, juvenile mice had augmented airway inflammation to allergen exposures. The study demonstrates that immunization dose, sex and age are highly influential on allergy outcomes. To better mimic different life stages of human allergic airway disease, murine models, therefore, require careful optimization.     

The effects of endotoxin pretreatment on subsequent challenge of mice with cycloheximide and a small dose of endotoxin

Mice treated with 15.0 micrograms of S. enteritidis endotoxin are completely protected against the coagulopathic effects, but only partially protected against the fatal glucocorticoid deficiency which follow an otherwise lethal challenge with cycloheximide and 5.0 micrograms of the same endotoxin given 3 days later. Hydrocortisone treatment results in survival of all such tolerant, challenged animals. The protection conferred against occlusion of glomerular capillaries by fibrin coagula is abolished by EACA, suggesting that tolerance has induced high levels of fibrinolytic activity by the time of challenge, and evidence indicates that this protective degree of fibrinolytic activity persists for more than 24 h after cycloheximide and endotoxin challenge.     

Genetic effects on anger control and their interaction with alcohol intoxication: A self-report study

Individual differences in anger control are important to consider when trying to understand intoxicated aggression (Parrott and Giancola, 2004). We explored, first, genetic and environmental effects on anger control both in self-reported sober and alcohol intoxicated states, and whether the same genetic and environmental effects influence it in both these states, and second, a possible interaction between genetic effects and alcohol in the control of anger. In the population based sample (N = 8964) of Finnish twins (18-33 years) and their siblings (18 years or older), genetic effects on anger control were found both for the self-reported sober (27% for men, 34% for women) and alcohol intoxicated states (29% for men, 37% for women), with high genetic correlations (from .77 to .85) between these states. Genetic effects (26% for men, 29% for women) were also found for the difference in anger control between the self-reported sober and alcohol intoxicated states, suggesting the effect of alcohol on anger control depends on the genotype of the individual.     

The effects of host age, virus dose, and virus strain on heterologous rotavirus infection of suckling mice

Seven-day-old suckling CD-1 mice, born to seronegative dams, were orally inoculated with a number of animal and human rotaviruses. Simian (SA11), rhesus (RRV), and bovine (B223) rotaviruses were found to replicate and cause severe disease. Canine (K9), bovine (B641), and human (Wa) rotaviruses either replicated minimally and caused minimal disease (K9, B641) or failed to replicate or cause disease (Wa). The features of SA11 infection of mice were examined in greater detail. Suckling mice were susceptible to infection and disease from 1 day of age to 13-15 days of age. Restriction of disease occurred at an earlier age (13 days) than restriction of replication (15 days). Dose-response studies in seven-day-old mice showed that virus replication and disease could be induced with doses as low as 1 x 10(2) pfu/mouse; however, both intestinal virus titers and severity of disease increased in parallel with virus dose. Intestinal virus replication appeared to be restricted in SA11 infections. Only at very low doses (1 x 10(2) pfu/mouse) did virus replication occur to levels above the inoculated dose. While light microscopic examination showed classical features of rotavirus infection in the ileum, electron microscopic examination revealed only the accumulation of large numbers of electron-lucent vacuoles in the ileal enterocytes of infected mice. Structures typical of rotavirus morphogenesis were not detected in enterocytes from mice infected with rotavirus SA11.     

The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection

Introduction

Helicobacter pylori infection is associated with decreased alcohol dehydrogenase (ADH) activity in the gastric mucosa. The decrease in gastric ADH activity depends on the severity of inflammation and mucosal injury. This damage can be a reason of the release of enzyme from gastric mucosa and leads to the increase of the ADH activity in the sera of patients with H. pylori infection.

Material and methods

Serum samples were taken from 140 patients with H. pylori infection. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate.

Results

The activity of ADH IV in the serum of patients with H. pylori infection increased about 42% (7.86 mU/l) in the comparison to the control level (4.52 mU/l). Total activity of ADH was 1105 mU/l in patients group and 682 mU/l in control. The diagnostic sensitivity for ADH IV was 88%, specificity 90%, positive and negative predictive values were 91% and 84% respectively. Area under ROC curve for ADH IV was 0.84.

Conclusions

Helicobacter pylori infection of gastric mucosa is reflected in the serum by significant increase of class IV and total ADH activity. The results suggest a potential role for ADH IV as a marker of H. pylori infection.     

The effects of social demand on breast self-examination self-report

The measurement of breast self-examination (BSE) adherence typically relies on verbal self-report. These studies systematically manipulated social demand within a face-to-face interview and examined the effects on self-reported BSE frequency. In Study 1, subjects (n=37) received either a high-demand or a low-demand preface prior to being asked about BSE practice over the past year. Study 2 (n=89) was a replication, with the addition of a no-preface (control) condition. Results from Study 1 indicated that although the conditions were comparable on demographic and breast cancer/BSE knowledge variables, the high-demand condition reported a significantly higher number of BSEs than the low-demand condition. An attenuation of this pattern was found in Study 2, with the control condition reporting a frequency between the low demand's and the high demand's reported frequencies. The implications for BSE intervention and prevalence research are discussed.     

急性饮酒对青年心率变异的影响及性别差异研究

目的通过检测轻度急性饮酒前后心率变异性指标,评价酒精对于自主神经活动影响的性别差异。方法20例健康志愿者．其中男性10例．年龄（20．1±0．6）岁：女性10例．年龄（19．6±0．8）岁。根据受试者体质量计算乙醇溶液饮用量（0．27g／kg）。分别在饮酒前和饮酒后15min、45min共3次记录心电信号．提取RR间期时间序列,计算心率变异性（HRV）评价指标,包括时域参数RR间期的平均值（RRI）、全部RR间期标准差（SDRR）、全程相邻RR间期之差的均方根（RMSSD）、相邻RR间期之差大于50ms的心搏动数占总心搏动数的比例（pNN50）,频域参数低频频段（LF）、高频频段（HF）和LF／HF,Poincar6图参数宽度（短轴,SDl）、长度（长轴,SD2）和SDl／SD2。结果时域参数、频域参数和P0inca诺参数存急性饮酒后降低。对于RMSSD和SDRR参数．仅在女性受试者中观测到饮酒45min后降低．差异均具有统计学意义（P〈0．05）。对于LF和SDl参数在饮酒后15min即观测到在男性受试者中降低,差异均具有统计学意义（P〈0．05）。结论少量的急性饮酒降低了心率变异程度．酒精抑制了副交感神经的活动度．女性比男性对酒精的敏感程度更高．男性自主种经活动对酒精影响的响应时间更短。