Genetic and environmental influences on illicit drug use and tobacco use across birth cohorts

BACKGROUND: The prevalence of use of many psychoactive substances has changed considerably in recent years. While genetic factors impact on overall risk for substance use, we know little about whether the etiological importance of these factors differs across birth cohorts. One theory, which postulates that heritability of deviant traits increases in permissive environments, predicts a positive relationship across cohorts between prevalence and heritability of substance use. METHOD: The lifetime history of use of tobacco, cannabis, cocaine, sedatives and stimulants were assessed in 4826 twins from male-male and female-female pairs born in Virginia from 1934 to 1974. Using empirical methods based on prevalence by birth year, these twins were divided into three cohorts for each substance (e.g. for cannabis 1934-1953, 1954-1968 and 1969-1974). Structural equation modeling was performed using the Mx software package. RESULTS: Prevalence rates for psychoactive substance use differed substantially across cohorts, most markedly for cocaine, sedatives and stimulants, which were highest in the 1958-1963 cohort. However, for all substances, the best-fit model constrained estimates of the etiological role of genetic and environmental risk factors to be equal across both sex and cohort. CONCLUSIONS: We found no evidence in this sample for any systematic relationship between heritability and prevalence of psychoactive substance use--which should be a rough index of drug availability and/or acceptability. This sample had reasonable power to detect large changes in heritability across cohorts and at least moderate power to detect relatively small changes.     

Predictive value of the early clinical signs in Rett disorder

The British Isles Survey for Rett has registered 1,159 cases over up to 20 years. Indicators of health and severity, recorded at intervals throughout life, are drawn from clinical examinations, reports and postal questionnaires. This study aimed to establish the stability and predictive value of an early severity score based on muscle tone, locomotor ability, feeding difficulty, scoliosis and epilepsy. Data from people with clinically documented classic or non-classic Rett and health records over 20-30 years indicate that severity scores tend to increase throughout the first 15 years and then to stabilise in mild and severe, classic and non-classic Rett. Severity scores before regression reflect later severity scores within relatively wide inter-quartile ranges. In general, the adult severity level is around 40 points above the pre-regression level for classic Rett and around 20 points for non-classic Rett. High early severity scores are associated with reduced cumulative survival. Used with caution, early signs are helpful in diagnosis and prognosis. The mutations T158M, R255X and R168X are generally associated with more severe and R306C and R133C with less severe disease but exceptions make these unreliable predictors of outcome.     

Anorexia nervosa mortality in Northeast Scotland, 1965-1999

OBJECTIVE: Most previous studies of mortality in anorexia nervosa patients have shown an increased risk of premature death but have been limited by methodological constraints. This study aimed to overcome some of these constraints by having a large original sample size, diagnosis confirmed by case note review, a long duration of follow-up, and a clear base population. METHOD: The authors identified 524 anorexia nervosa cases seen in specialist services in Northeast Scotland; anorexia nervosa diagnosis was confirmed by scrutinizing case notes. Those who had died were identified from the National Health Service register or register of deaths. The death rates and causes of death were analyzed. RESULTS: Twenty-three patients died, giving a crude death rate of 4.4% and a standardized mortality rate of 3.3 (95% CI=2.2-4.9). In only one-third of the cases was anorexia nervosa on the death certificate, but an eating disorder or other psychiatric pathology probably contributed to several of the other deaths. Older age at the time the patient was seen at the specialist service was the only identifiable risk factor in the group of patients who died. The median length of time between diagnosis and death was 11 years. CONCLUSIONS: Anorexia nervosa is associated with increased risk of premature death. It is possible that death rates could be reduced by early diagnosis and by long-term specialist care.     

Aicardi syndrome in a girl with mild developmental delay, absence of epilepsy and normal EEG

We report a 6-year-old girl with corpus callosum agenesis and other cerebral malformations, scoliosis and hypopigmented chorioretinal lacunae in both fundi typical of Aicardi syndrome. She has never had epilepsy and the EEG has always been normal, observations not reported previously in Aicardi syndrome. She was mildly mentally retarded with a full scale IQ of 61. The patient exhibited an unusually mild Aicardi syndrome phenotype.     

Sincalide in patients with parenteral nutrition-associated gallbladder disease

OBJECTIVE: To review the role of sincalide in treating and preventing parenteral nutrition (PN)-associated gallbladder disease. DATA SOURCES: A MEDLINE (1996-March 2004) search was performed using the key terms cholecystokinin, sincalide, parenteral nutrition, cholelithiasis, cholestasis, and sludge. DATA SYNTHESIS: Five human studies investigated the safety and efficacy of sincalide in patients with PN-associated gallbladder disease. Sincalide at intravenous doses of 0.04 microg/kg 3 times daily increased bile flow and improved serum bilirubin levels. However, patients with advanced liver disease did not respond to sincalide therapy. Long-term follow-up data on sincalide effects on liver disease progression are not yet available. CONCLUSIONS: Sincalide improved the signs of cholestasis. However, its long-term effects in preventing and treating PN-associated gallbladder disease remain unknown and its routine use for this indication cannot be recommended at this time.     

The potential role of HMG-CoA reductase inhibitors in pediatric nephrotic syndrome

OBJECTIVE: To evaluate the safety and efficacy of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as a potential treatment option for the dyslipidemia associated with childhood nephrotic syndrome. DATA SOURCES: Searches of MEDLINE (1966-April 2004), Cochrane Library, International Pharmaceutical Abstracts (1977-April 2004), and an extensive manual review of journals were performed using the key search terms nephrotic syndrome, familial hypercholesterolemia, dyslipidemia, and HMG-CoA reductase inhibitor. STUDY SELECTION AND DATA EXTRACTION: Two prospective uncontrolled studies evaluating the safety and efficacy of statin therapy in pediatric nephrotic syndrome were included. DATA SYNTHESIS: While an extensive amount of data is available in adult nephrotic syndrome in which statin therapy decreases total plasma cholesterol 22-39%, low-density lipoprotein cholesterol (LDL-C) 27-47%, and total plasma triglycerides 13-38%, only 2 small uncontrolled studies have been conducted evaluating the utility of these agents in pediatric nephrotic syndrome. These studies indicate that statins are capable of safely reducing total cholesterol up to 42%, LDL-C up to 46%, and triglyceride levels up to 44%. CONCLUSIONS: Lowering cholesterol levels during childhood may reduce the risk for atherosclerotic changes and may thus be of benefit in certain patients with nephrotic syndrome. Statins have demonstrated short-term safety and efficacy in the pediatric nephrotic syndrome population. Implementing pharmacologic therapy with statins in children with nephrotic syndrome must be done with care until controlled studies are conducted in this population.