Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort.

BACKGROUND: Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. METHODS: We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. RESULTS: Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. CONCLUSION: Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.

Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior.

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

Insulin infusions in the neonatal unit: delivery variation due to adsorption.

OBJECTIVE: To assess the extent of the variability in insulin delivery over time, under conditions used in Australian neonatal units, studying the following variables: diluent, preconditioning, flushing, sequential preconditioning and flushing, insulin concentration, flow rate, catheter type, and addition of albumin. METHODOLOGY: A range of simulated insulin infusions was studied. Infusions were run over 22 h, with aliquots of infusate collected at baseline and after 15 min, 30 min, 1 h, 2 h, 6 h and 22 h. Insulin concentration was assayed using a radioimmunoassay. RESULTS: An infusion of 50 mU insulin/mL at 1 mL/h gave negligible insulin delivery until 22 h. However, after preconditioning and flushing the tubing, consistent insulin delivery was attained by 6 h. An infusion of 200 mU insulin/mL at 1 mL/h did not provide consistent delivery until 6 h. At this concentration and rate, consistent insulin delivery was attained within 30 min of the start of the infusion either by preconditioning and flushing the tubing, or by addition of albumin to the infusate. CONCLUSION: Clinically significant variation in intravenous insulin delivery will occur in the neonatal setting unless counter-measures are taken, such as sequential preconditioning and flushing of the delivery system or the addition of albumin to the infusate.

Association of burners with cervical canal and foraminal stenosis.

The purpose of this study was to determine whether the burner phenomenon is associated with cervical canal and foraminal stenosis in a scholastic population. Lateral cervical radiographs were reviewed for 64 athletes, 15 to 18 years of age, who had sustained at least one burner. Controls consisted of age-matched athletes who had sustained head or neck trauma without evidence of the burner phenomenon (N = 32). Pavlov ratios were calculated for levels C-3 through C-6; both mean minimum and mean average ratios were determined. Available oblique radiographs from both the study (N = 31) and control (N = 15) groups were then used to calculate the foramen/vertebral body ratio--a measure of relative foraminal height. Significant differences were found between the burner and control groups for the mean minimum and mean average Pavlov ratios and foramen/vertebral body ratios. Scholastic athletes sustaining the burner phenomenon have an increased risk of cervical canal and foraminal stenosis as measured by the Pavlov and foramen/vertebral body ratios, respectively. The foramen/vertebral body ratio is an easily reproducible and reliable means of assessing foraminal dimensions from oblique radiographs and controls for x-ray magnification and rotation. Foraminal stenosis assessment may prove useful in predicting burner risk, especially in athletes with extension-compression injuries.

Accuracy of pedicle screw placement with the assistance of lateral plain radiography.

To determine the accuracy of pedicle screw placement with the assistance of lateral plain radiography, a prospective study was performed between June 1991 and March 1994 on patients who had undergone pedicle screw fixation of their thoracolumbar spine for degenerative and traumatic conditions. Sixty-five of 72 patients had the appropriate imaging studies, including an intraoperative lateral plain radiograph and a post-operative computed tomography scan to evaluate pedicle screw placement. A total of 238 screws were inserted from the T11 to L5 vertebral levels. Twenty-four screws penetrated the pedicle wall (18 medial and 6 lateral) and two screws penetrated the anterior vertebral body cortex, for an overall 89.1% success rate. Only two patients had neurologic complications consistent with canal intrusion of a pedicle screw, corresponding to a 0.84% neurologic complication rate. Imaging techniques such as fluoroscopy and anteroposterior plain radiographs, which may increase the incidence of infection from prolonged operative time, are unnecessary in uncomplicated cases. Pedicle screw insertion in the thoracolumbar spine with the use of lateral plain radiography alone is safe and effective, and it minimizes operative time and expense.

Delivery of vitamin A from parenteral nutrition solutions in neonates.

The delivery of Vitamin A from parenteral nutrition may be suboptimal. To investigate this sample solutions were prepared and Vitamins A and E concentrations from the solution bags and the efflux from the lines were measured over a 24 h period. The results show that mean Vitamin A levels in the solution bags declined from a range of 57-66% to 17% of expected over 24 h and at the efflux of the lines from a range of 13-29% to 4% of expected, giving a calculated delivery of 10% of expected. There is no improvement with light protection or an ethylene vinyl acetate system. Mixing the vitamin preparation in lipid showed less decline (from 92 to 70% of expected over 24 h), but the delivery was variable. When vitamins were added to a lipid-dextrose-amino acid solution, there was minimal loss from the solution bag and line with a calculated delivery of 94% of expected. The delivery of Vitamin E from all systems was constant with a mean calculated delivery of 74% of expected. It was concluded that the mixing of multivitamins in dextrose-amino acid-electrolyte solutions results in poor delivery of Vitamin A and this is improved by mixing lipid solution. This is important in preterm infants who are prone to become Vitamin A deficient.

The psychological aspects of artificial nutritional support.

Patients receiving artificial nutritional support are subject to ongoing psychological stress. They are often physically ill, are required to follow a rigid dietary regime and, by necessity, are involved in an ongoing relationship with members of the treating team. This paper presents examples of the clinical problems and discusses the role of the psychiatrist as a member of the multidisciplinary team.

Parenteral nutrition: current status and concepts.

Parenteral nutrition is regarded as a form of nutrition in some countries and as an extension of intravenous fluid therapy in others. The optimum clinical application of parenteral nutrition as a form of therapy requires detailed knowledge of the nutrient solutions themselves, including the commonly used solutions such as dextrose, soybean oil emulsion, synthetic crystalline L-amino acid solutions; older solutions such as xylitol, protein hydrolysates; and newer solutions such as glycerides and special purpose amino acid solutions. Additionally, information has accumulated over the past 10 years, leading to the rational use of vitamins and trace elements in parenteral nutrition. Metabolism of the substrates has been correlated with known pathways of intermediary metabolism in normal, starved and stressed subjects. Several new concepts have arisen: a) Infusion of excessive quantities of dextrose results in lipogenesis and increased carbon dioxide production. Hyperalimentation of this type is being replaced by infusion of lesser quantities of dextrose, supplemented by intravenous infusion of lipid as a calorie source. b) Protein hydrolysates and racemic synthetic crystalline amino acid solutions have been replaced by synthetic crystalline L-amino acid solutions. c) A new fat emulsion based on safflower oil is competing successfully with the traditional soybean oil emulsion. d) Newer substrates are being explored. These include branched chain amino acids, keto analogues of amino acids, synthetic glycerides and maltose. e) Deficiencies of essential fatty acids, trace elements and vitamins have been studied in patients on long term parenteral nutrition and their mechanisms elucidated. Official recommendations for intravenous administration of these nutrients have been made. f) Several techniques have been applied in several circumstances, including protein sparing therapy, cyclic nutrition, home therapy, and parenteral nutrition in liver and renal failure. Parenteral nutrition is now used extensively, not only in major hospitals where the resources of a team approach with physician, nurse, pharmacist and dietitian are available, but also in smaller hospitals where all of these facilities may not be at hand. However, whatever the setting, the principles behind the clinical application of parenteral nutrition should be well understood by those involved, including current approaches to safe preparation and infusion of parenteral nutrition solutions.

A survey of cephalosporin use. Monitoring use in a hospital setting.

A survey of cephalosporin use was conducted at Flinders Medical Centre, a teaching hospital incorporating most specialty services. All in-patients who were prescribed cephalosporins over a seven-week period were monitored, and an evaluation of appropriateness of use was made by means of defined criteria. The cost of usage was also determined. During the study, 55 patients were given 57 courses of cephalosporins. In 59% of courses a cephalosporin was not the drug of choice; this figure comprised 42% of 33 therapeutic and 71% of 24 prophylactic courses. In most cases, the appropriate drug would have been a penicillin, usually a penicillinase-resistant penicillin. Prophylactic courses were often longer than normal recommendations. Each course cost approximately $25, about twice that of more appropriate drugs. It is suggested that future criteria-based reviews should be conducted to identify practice deficiencies, and that guidelines for antibiotic use be created.