Developmental language disorders--a follow-up in later adult life. Cognitive, language and psychosocial outcomes

BACKGROUND: Little is known on the adult outcome and longitudinal trajectory of childhood developmental language disorders (DLD) and on the prognostic predictors. METHOD: Seventeen men with a severe receptive DLD in childhood, reassessed in middle childhood and early adult life, were studied again in their mid-thirties with tests of intelligence (IQ), language, literacy, theory of mind and memory together with assessments of psychosocial outcome. They were compared with the non language disordered siblings of the DLD cohort to control for shared family background, adults matched to the DLD cohort on age and performance IQ (IQM group) and a cohort from the National Child Development Study (NCDS) matched to the DLD cohort on childhood IQ and social class. RESULTS: The DLD men had normal intelligence with higher performance IQ than verbal IQ, a severe and persisting language disorder, severe literacy impairments and significant deficits in theory of mind and phonological processing. Within the DLD cohort higher childhood intelligence and language were associated with superior cognitive and language ability at final adult outcome. In their mid-thirties, the DLD cohort had significantly worse social adaptation (with prolonged unemployment and a paucity of close friendships and love relationships) compared with both their siblings and NCDS controls. Self-reports showed a higher rate of schizotypal features but not affective disorder. Four DLD adults had serious mental health problems (two had developed schizophrenia). CONCLUSION: A receptive developmental language disorder involves significant deficits in theory of mind, verbal short-term memory and phonological processing, together with substantial social adaptation difficulties and increased risk of psychiatric disorder in adult life. The theoretical and clinical implications of the findings are discussed.     

Incidence of autism spectrum disorders: changes over time and their meaning

Aim: Several reviews have noted a huge increase in the rate of diagnosed autism spectrum disorders. The main aims of this paper are: 1) to use published empirical findings to consider whether the rise reflects a true increase in incidence, as distinct from the consequences of better ascertainment and a broadening of the diagnostic concept; and 2) to consider how epidemiological data may be used to test hypotheses about possible causal influences, using MMR and thimerosal as examples. Methods: Search of the literature for studies with a large epidemiological base population, systematic standardized screening, a focus on an age group for which diagnostic assessments are reliable and valid, and diagnosis by trained professionals using high-quality research assessments. Also, search of a broader literature to consider the evidence from all epidemiological studies with respect to the hypothesized causal effect of MMR and thimerosal on autism spectrum disorders. Results: The true incidence of autism spectrum disorders is likely to be within the range of 30-60 cases per 10 000, a huge increase over the original estimate 40 years ago of 4 per 10 000. The increase is largely a consequence of improved ascertainment and a considerable broadening of the diagnostic concept. However, a true risk due to some, as yet to be identified, environmental risk factor cannot be ruled out. There is no support for the hypothesis for a role of either MMR or thimerosal in causation, but the evidence on the latter is more limited.

Conclusion: Progress in testing environmental risk hypotheses will require the integration of epidemiological and biological studies.     

Role for plasma membrane-related Ca2+-ATPase-1 (ATP2C1) in pancreatic beta-cell Ca2+ homeostasis revealed by RNA silencing

Changes in intracellular Ca(2+) concentration play a key role in the regulation of insulin secretion by glucose and other secretagogues. Here, we explore the importance of the secretory pathway Ca(2+)-ATPase, plasma membrane-related Ca(2+)-ATPase-1 (PMR1; human orthologue ATP2C1) in intracellular Ca(2+) homeostasis in pancreatic islet beta-cells. Endogenous PMR1 mRNA and protein were detected in both isolated rat islets and beta-cell-derived lines (MIN6 and INS1). Subcellular fractionation of the cell lines revealed PMR1 immunoreactivity in both microsomal and dense-core secretory vesicle-enriched fractions. Correspondingly, depletion of cellular PMR1 with small interfering RNAs inhibited Ca(2+) uptake into the endoplasmic reticulum and secretory vesicles by approximately 20%, as assessed using organelle-targeted aequorins in permeabilized INS1 cells. In intact cells, PMR1 depletion markedly enhanced flux though L-type Ca(2+) channels and augmented glucose-stimulated, but not basal, insulin secretion. Whereas average cytosolic [Ca(2+)] increases in response to 30.0 mmol/l glucose were unaffected by PMR1 depletion, [Ca(2+)] oscillation shape, duration, and decay rate in response to glucose plus tetraethylammonium were modified in PMR1-depleted single cells, imaged using fluo-3-acetoxymethylester. PMR1 thus plays an important role, which is at least partially nonoverlapping with that of sarco(endo-)plasmic reticulum Ca(2+)-ATPases, in the control of beta-cell Ca(2+) homeostasis and insulin secretion.     

Effect of breast augmentation on the accuracy of mammography and cancer characteristics

Context  Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation. Objective  To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation. Design, Setting, and Participants  A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10 533 women with augmentation and 974 915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt. Main Outcome Measures  Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status. Results  Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval {CI}, 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P = .008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P = .052) for women with breast augmentation vs without. Conclusions  Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation.      

Genetic and environmental risk factors in adolescent substance use

BACKGROUND: The present study was undertaken with the goal of understanding the causes of association between substance use and both conduct disturbance (CD) and depression in adolescent boys and girls. METHOD: Multivariate genetic structural equation models were fitted to multi-informant, multi-wave, longitudinal data collected in extensive home interviews with parents and children with respect to 307 MZ male, 392 MZ female, 185 DZ male, and 187 DZ female, same-sex twin pairs aged 12-17 years from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). RESULTS: Although conduct disturbance and depression were moderately associated with substance use, the pattern of genetic and environmental risk differed for males and females and across the two disorders. Genetic factors were predominant in girls' substance use whereas boys' use was mediated primarily by shared environmental factors reflecting family dysfunction and deviant peers. The patterns of correlations across the two waves of the study were consistent with conduct disturbance leading to substance use in both males and females, but depression leading to smoking, drug use and, to a lesser extent, alcohol use in girls. CONCLUSIONS: The comorbidity between substance use and depression, and between substance use and conduct disturbance in childhood/adolescence, probably reflects rather different mediating mechanisms--as well as a different time frame, with conduct disturbance preceding substance use but depression following it. In both, the co-occurrence partially reflected a shared liability but, in girls, genetic influences played an important role in the comorbidity involving depression, whereas in both sexes (but especially in boys) environmental factors played a substantial role. The extent to which these differences reflect genuine differences in the causal mechanisms underlying substance use and CD/depression in boys and girls revealed in the present analysis awaits replication from studies of other general population samples.