Mathematics anxiety in children with developmental dyscalculia

Background  

Math anxiety, defined as a negative affective response to mathematics, is known to have deleterious effects on math performance in the general population. However, the assumption that math anxiety is directly related to math performance, has not yet been validated. Thus, our primary objective was to investigate the effects of math anxiety on numerical processing in children with specific deficits in the acquisition of math skills (Developmental Dyscalculia; DD) by using a novel affective priming task as an indirect measure.     

Children in Residential Group Care With No Family Ties: Facing Existential Aloneness

The issue of children living in residential group care in Israel completely without family ties is studied in order to explore the feelings of staff and uncover possible characteristics of these children. Data were collected through focus groups, questionnaires, and life stories of children who left group care at 18 years of age. Results reveal that the children's aloneness is central in their lives and arouses painful and powerful emotions that staff members tend to avoid. Facing the future alone without support and guidance led to major crisis during adolescence. Those who had formed a long-term, significant relationship with an adult fared better.     

The Novel Cholinesterase–Monoamine Oxidase Inhibitor and Antioxidant,Ladostigil, Confers Neuroprotection in Neuroblastoma Cells and Aged Rats

The current therapeutic advance in which future drugs are designed to possess varied pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil (TV3326; (N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate). Ladostigil combines neuroprotective effects with monoamine oxidase (MAO)-A and MAO-B and cholinesterase (ChE) inhibitory activities in a single molecule, as a potential treatment for Alzheimer’s disease (AD) and Lewy body disease. In the present study, we demonstrate that ladostigil (10⁻⁶–10 μM) dose-dependently increased cell viability, associated with increased activity of catalase and glutathione reductase and decrease of intracellular reactive oxygen species production in a cytotoxic model of human SH-SY5Y neuroblastoma cells exposed to hydrogen peroxide (H₂O₂). In addition, ladostigil significantly upregulated mRNA levels of several antioxidant enzymes (catalase, NAD(P)H quinone oxidoreductase 1 and peroxiredoxin 1) in both H₂O₂-treated SH-SY5Y cells, as well as in the high-density human SK-N-SH neuroblastoma cultured apoptotic models. In vivo chronic treatment with ladostigil (1 mg/kg per os per day for 30 days) markedly upregulated mRNA expression levels of various enzymes involved in metabolism and oxidation processes in aged rat hippocampus. In addition to its unique combination of ChE and MAO enzyme inhibition, these results indicate that ladostigil displays neuroprotective activity against oxidative stress-induced cell apoptosis, which might be valuable for aging and age-associated neurodegenerative diseases. Orit Bar-Am, Orly Weinreb, and Tamar Amit share equal recognition.     

Co-transmission of conduct problems with attention-deficit/hyperactivity disorder: familial evidence for a distinct disorder

Summary Common disorders of childhood and adolescence are attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). For one to two cases in three diagnosed with ADHD the disorders may be comorbid. However, whether comorbid conduct problems (CP) represents a separate disorder or a severe form of ADHD remains controversial. We investigated familial recurrence patterns of the pure or comorbid condition in families with at least two children and one definite case of DSM-IV ADHDct (combined-type) as part of the International Multicentre ADHD Genetics Study (IMAGE). Using case diagnoses (PACS, parental account) and symptom ratings (Parent/Teacher Strengths and Difficulties [SDQ], and Conners Questionnaires [CPTRS]) we studied 1009 cases (241 with ADHDonly and 768 with ADHD + CP), and their 1591 siblings. CP was defined as ≥4 on the SDQ conduct-subscale, and T ≥ 65, on Conners’ oppositional-score. Multinomial logistic regression was used to ascertain recurrence risks of the pure and comorbid conditions in the siblings as predicted by the status of the cases. There was a higher relative risk to develop ADHD + CP for siblings of cases with ADHD + CP (RRR = 4.9; 95%CI: 2.59–9.41); p < 0.001) than with ADHDonly. Rates of ADHDonly in siblings of cases with ADHD + CP were lower but significant (RRR = 2.9; 95%CI: 1.6–5.3, p < 0.001). Children with ADHD + CP scored higher on the Conners ADHDct symptom-scales than those with ADHDonly. Our finding that ADHD + CP can represent a familial distinct subtype possibly with a distinct genetic etiology is consistent with a high risk for cosegregation. Further, ADHD + CP can be a more severe disorder than ADHDonly with symptoms stable from childhood through adolescence. The findings provide partial support for the ICD-10 distinction between hyperkinetic disorder (F90.0) and hyperkinetic conduct disorder (F90.1). The first two authors contributed equally to this paper. Correspondence: Robert D. Oades, Clinic for Child and Adolescent Psychiatry and Psychotherapy, The University of Duisburg-Essen, Virchowstr. 174, 45147 Essen, Germany     

Prolidase deficiency associated with systemic lupus erythematosus (SLE): single site experience and literature review

ABSTRACT: INTRODUCTION: Prolidase deficiency (PD) is a rare autosomal recessive disorder which may have a wide spectrum of clinical features. These features include a characteristic facies, cognitive impairment, rashes or skin ulceration, splenomegaly, recurrent infections involving mainly the respiratory system, and iminodipeptiduria. The disorder is caused by a mutation in the PEPD gene. OBJECTIVE: To describe a cohort of unrelated PD patients from Northern Israel whose inborn error of metabolism was associated with systemic lupus erythematosus (SLE) and to identify in the medical literature all PD cases mimicked by and/or associated with SLE. METHODS: Three patients with PD associated with SLE were clinically, biochemically and genetically investigated. These patients were from 3 unrelated consanguineous families residing in Northern Israel. A computer-assisted (PubMed) search of the medical literature from 1975 to 2011 was performed using the following key words: Prolidase deficiency, SLE, and systemic lupus erythematosus. RESULTS: An association between PD and SLE was found in 10 PD patients. These 10 patients included three from our cohort of 23 PD patients, and seven out of just under 70 PD patients previously reported in the literature. CONCLUSION: The present findings underscore the relatively high incidence of the association between SLE and PD, suggesting that this association may not be coincidental. The phenotypic similarities between SLE and PD might suggest that the PEPD gene constitutes a modifier gene or a genetic risk factor in the causation of SLE.     

Tau's role in the developing brain: implications for intellectual disability

Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.     

MARK2/Par-1 guides the directionality of neuroblasts migrating to the olfactory bulb

In rodents and most other mammals studied, neuronal precursors generated in the subventricular zone (SVZ) migrate to the adult olfactory bulb (OB) to differentiate into interneurons called granule and periglomerular cells. How the newborn cells navigate in the postnatal forebrain to reach precisely their target area is largely unknown. However, it is often thought that postnatal neurogenesis recapitulates the neuronal development occurring during embryogenesis.During brain development, intracellular kinases are key elements for controlling cell polarization as well as the coupling between polarization and cellular movement. We show here that the polarity kinase MARK2 maintains its expression in the postnatal SVZ-OB system. We therefore investigated the potential role of this kinase in adjusting postnatal neuroblast migration. We employed mouse brain slices maintained in culture, in combination with lentiviral vector injections designed to label neuronal precursors with GFP and to diminish the expression of MARK2. Time-lapse video microscopy was used to monitor neuroblast migration in the postnatal forebrain from SVZ precursors to cells populating the OB.We found that reduced MARK2 expression resulted in altered migratory patterns and stalled neuroblasts in the rostral migratory stream (RMS). In agreement with the observed migratory defects, we report a diminution of the proportion of cells reaching the OB layers. Our study reveals the involvement of MARK2 in the maintenance of the migratory direction in postnatally-generated neuroblasts and consequently on the control of the number of newly-generated neurons reaching and integrating the appropriate target circuits.     

Cancer Risk After Exposure to Treatments for Ovulation Induction

Uncertainty continues as to whether treatments for ovulationinduction are associated with increased risk of cancer. Theauthors conducted a long-term population-based historical cohortstudy of parous women. A total of 15,030 women in the JerusalemPerinatal Study who gave birth in 1974–1976 participatedin a postpartum survey. Cancer incidence through 2004 was analyzedusing Cox's proportional hazards models, controlling for ageand other covariates. Women who used drugs to induce ovulation(n = 567) had increased risks of cancer at any site (multivariatehazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06,1.74). An increased risk of uterine cancer was found among womentreated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28,8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34).No association was noted between use of ovulation-inducing agentsand ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42).Ovulation induction was associated with a borderline-significantincreased risk of breast cancer (multivariate HR = 1.42, 95%CI: 0.99, 2.05). Increased risks were also observed for malignantmelanoma and non-Hodgkin lymphoma. These associations appearedstronger among women who waited more than 1 year to conceive.Additional follow-up studies assessing these associations bydrug type, dosage, and duration are needed. breast neoplasms; cohort studies; incidence; lymphoma, non-Hodgkin; melanoma; ovarian neoplasms; ovulation induction; uterine neoplasms