Fragile X syndrome: Neural network models of sequencing and memory

A comparative framework of memory processes in males with fragile X syndrome (FXS) and typically developing (TYP) mental age-match children is presented. Results indicate a divergence in sequencing skills, such that males with FXS recall sequences similarly to TYP children around five and a half years of age, but the males with FXS recall significantly worse when compared to TYP children around seven and a half years of age. Performance on one working memory measure, an n-back Card Task, is modeled with a neural network. To date, no network models explicate the sequencing and memory processes in those with FXS. Noise was added to various levels (weight matrices) in the FXS model and outputs approximated human FXS performance. Three models were compared: (1) FXS; (2) younger mental age-TYP matches; (3) older reading level-TYP matches. Modeling can help to reify conceptualizations of deficits and to guide in the creation of more valid, science-based remediations. The FXS model suggested that the levels of phonological representation and sequencing in memory were candidates for targeted therapies in males with FXS.     

中医证实质研究的困惑及出路

根据中医证实质研究的现状,分析了证实质研究存在困惑的原因,并提出证的诊断标准化以及走病证结合的研究之路是中医证实质研究的出路。     

The Psychological Burden Inflicted By Multiple Cancers in Li-Fraumeni Families: Five Case Studies

To gain insight into the psychological, emotional, relational, and family problems of families afflicted by Li-Fraumeni syndrome, we interviewed members of five such families in the Pediatric Oncology Department, Gustave Roussy Institute, where at least one member of the family had been treated. These interviews showed that families were psychologically fragile, that their interactions and thinking patterns were related to a family background plagued by the repeated occurrence of cancer, and was often marked by physical or psychological violence. They had complex imaginary etiologic explanations, and showed an ambivalent willingness to learn about cancer and the risks involved. They expressed their fear of transmitting doom and death, posed questions about whether their parents would have had them had they known the test result, and about what their own attitude would be toward childbearing. Thus genetic testing awoke disconcerting and unsolved questions for them. These first results can contribute to the design of supportive interventions and future clinical research.     

An Opportunity for Genetic Counseling Intervention: Depression in Parents of Individuals with Proteus Syndrome

Depression is common, affecting 2–5% of the general population. Parental depression can confound adjustment to, and caring for, a child with a genetic condition. As part of a study on psychosocial issues of parents caring for children with Proteus syndrome, 31 parents (20 mothers and 11 fathers) completed a depression screening tool, the Beck Depression Inventory. Approximately 23% (4/20 mothers and 3/11 fathers) scored positive on the tool. Pessimism, sense of failure, general lack of satisfaction, sense of punishment, self-dislike, social withdrawal, indecisiveness, work inhibition, somatic preoccupation, and loss of libido were reported more frequently by the group of parents with positive screen results than those with normal results. These data suggest that symptoms of depression may be prevailing among parents of individuals with Proteus syndrome. Because effective interventions for depression are readily available, genetic counselors working with families affected with rare, overgrowth disorders should specifically assess parents for physical and affective symptoms of depression and refer them for appropriate clinical treatment.     

The relationships among verbal short-term memory, phonological awareness, and new word learning: evidence from typical development and Down syndrome

This study examined the correlates of new word learning in a sample of 64 typically developing children between 5 and 8 years of age and a group of 22 teenagers and young adults with Down syndrome. Verbal short-term memory and phonological awareness skills were assessed to determine whether learning new words involved accurately representing phonological information in memory. Results showed a relationship between verbal short-term memory measures and typically developing individuals’ ability to learn the phonological form of novel words but not their ability to learn the physical referent of new words. Similarly, individuals with Down syndrome showed impaired verbal short-term memory and impaired form but not referent learning. Together, these findings specify the circumstances in which an accurate phonological representation within short-term memory is required for new word learning.     

Social Information Processing Skills in Children with Histories of Heavy Prenatal Alcohol Exposure

Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge’s reformulated six-stage model. Fifty-two children (aged 7–11) with and without heavy prenatal alcohol exposure were tested using a structured interview measure of social information processing involving 18 videotaped vignettes of children in group entry and provocation situations. Alcohol-exposed children displayed maladaptive processing patterns on the goal, response generation, and response evaluation steps in group entry situations, and encoding, attribution, response evaluation, and enactment steps during provocation situations. Children with heavy prenatal alcohol exposure also had difficulty on the Test of Problem Solving, and performance correlated with social information processing measures. Such difficulties may lead to problems in social functioning and warrant early intervention.     

IQ in childhood and the metabolic syndrome in middle age: Extended follow-up of the 1946 British Birth Cohort Study

IQ in early adulthood has been inversely associated with risk of the metabolic syndrome in midlife. We tested this association in the British 1946 birth cohort, which assessed IQ at age eight years and ascertained the metabolic syndrome at age 53 years based on modified (non-fasting blood) ATPIII criteria. Childhood IQ was inversely associated with risk of the metabolic syndrome, but this association was almost entirely mediated by educational attainment and achieved occupational social class. This may be consistent with a pattern where childhood IQ is strongly associated with outcomes that reflect neurological disorder, such as the degenerative dementias, but less so with common chronic physical diseases of ageing.     

Chronic glucocorticoid hypersecretion in Cushing’s syndrome exacerbates cognitive aging

Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing’s syndrome (CS), a disorder characterized by chronic exposure to elevated levels of glucocorticoids (GC), is similar to that observed in older individuals. Ten subjects with CS were compared to sex-, age-, and education-matched healthy controls and older subjects (age of CS subjects + 15 yr). All participants were administered tests to assess attention, visuospatial processing, learning and memory, reasoning, concept formation and verbal fluency. MANCOVAs with depression scores as covariate and polynomial contrasts revealed that the age-matched control group performed better than the CS and older subject groups in visual target detection, trail making test, stroop task, digit symbol substitution, block design, object assembly, visual reproduction, spatial memory and similarities. The CS and older subjects performed similarly on these tasks. Further, a principal component analysis revealed two significant factors, representing general cognitive function and verbal memory explaining 39.9% and 10.0% of the variance, respectively. Additional MANCOVAs with depression as a covariate revealed that CS and older control subjects showed impaired performance on general cognitive function compared to age-matched controls. These results suggest that hypersecretion of GCs has “aging-like” effects on cognitive performance in individuals with CS.     

The trajectory of mathematics skills and working memory thresholds in girls with fragile X syndrome

Fragile X syndrome is a common genetic disorder associated with executive function deficits and poor mathematics achievement. In the present study, we examined changes in math performance during the elementary and middle school years in girls with fragile X syndrome, changes in the working memory loads under which children could complete a cognitive switching task, and the association between these two areas of function, in girls with fragile X syndrome relative to their peers. Our findings indicate that the trajectory of math and executive function skills of girls with fragile X differs from that of their peers and that these skills contribute to predicting math achievement and growth in math performance over time. Also, changes in math performance were associated with incremental increases in working memory demands, suggesting that girls with fragile X have a lower threshold for being able to perform under increasing task demands. Still, we found improvement in executive function performance between 10 and 12 years in girls with fragile X rather than a performance plateau as has been reported in other studies. The findings implicate the importance of early intervention in mathematics for girls with fragile X that addresses poor calculation skills, the supporting numerical skills, and deficits in executive functions, including working memory.     

Brief cognitive-behavioral internet therapy for irritable bowel syndrome

While cognitive-behavioral therapy for IBS is quite effective, the limited availability of competent therapists and lack of access to treatment remain problematic. This paper reports on a small, randomized, controlled trial of a five week internet based cognitive-behavioral intervention for IBS with limited therapist feedback via e-mail. Fifty-four IBS patients were recruited via the internet and randomly assigned to either immediate treatment or a wait-list control group. Thirty-one subjects completed the post-treatment assessment. 77% of treatment completers also completed a 3-month follow-up assessment. Treatment completers experienced statistically and clinically significant declines in IBS symptoms and improvements in quality of life. Those gains were substantially maintained at follow-up. Treatment efficacy was partially mediated by reductions in the tendency to catastrophize the social and occupational implications of symptoms, suggesting that catastrophizing may be an important target for treatment.