Louise O'Donnell

Developmental sex differences in verbal learning.

Although sex differences in verbal learning and memory have been reported in adults, much less is known about when these sex differences emerge and how they develop. In this study, 401 boys and 410 girls between the ages of 5 and 16 years were administered the California Verbal Learning Test--Childrens Version. Sex differences were found at all age levels. Girls performed better than boys on all of the immediate and delayed recall trials and on the delayed recognition trial. Girls were also more likely than boys to use a semantic clustering strategy and displayed more effective long-term memory mechanisms. Boys made more intrusion errors and displayed greater vulnerability to interference between the 2 test lists. Because boys had higher mean scores on Wechsler Intelligence Scale for Children--Revised Vocabulary, the observed female superiority in verbal learning could not be attributed to sex differences in overall word knowledge.

Influence of Subject Response Style Effects on Retrospective Measures

Recent attempts to reduce internal invalidity in studies employing pretest/posttest self-report in dices of improvement have included the refinement of methodologies employing retrospective reports of pre-treatment states. The present study investigated the operation of social desirability and impression management response bias on such retrospective measures. The results do not support the hypothesis of greater bias on retrospective measurement and, in fact, are in a direction that might suggest an in terpretation of reduced bias on such measures. The results also continue to support superior validity of retrospective over traditional pretest/posttest in dices of improvement following treatment.

Arithmetic Disabilities and ADD Subtypes Implications for DSM-IV

This study investigated whether specific academic deficits were associated with attention-deficit disorder (ADD) subtypes. Twenty students (ages 8-12) with attention-deficit disorder with hyperactivity (ADD/H) were compared to 20 students with attention-deficit disorder without hyperactivity (ADD/noH). Group differences were compared using a MANCOVA, and paired t tests were used to compare within-group differences. Dependent variables for the within-group differences were four achievement subtest scores from the Woodcock-Johnson Psycho-Educational Battery-Revised: Letter-Word Identification, Passage Comprehension, Calculation, and Applied Problems. Consistent with much of the previous research, no significant between-group differences were found on the achievement measures. Significant differences did, however, appear in the six within-group comparisons, all involving lower performance on the Math Calculations subtest. For students with ADD/H, only one comparison (with Math Applied Problems) reached significance. Students with ADD/noH, however, had significantly lower scores on the Calculation subtest compared to all of the other achievement subtests. These results provided additional support for the hypothesis that inattention exerts a specific and deleterious effect on the acquisition of arithmetic computation skills. These findings have important implications for the diagnosis and treatment of ADHD as conceptualized in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994), because they suggest that students with ADHD-Predominantly Inattentive Type may be at increased risk for arithmetic calculation deficits.

Tetrasomy 18p: report of the molecular and clinical findings of 43 individuals.

Thus far, the phenotype of tetrasomy 18p has been primarily delineated by published case series and reports. Findings reported in more than 25% of these cases include neonatal feeding problems, growth retardation, microcephaly, strabismus, muscle tone abnormalities, scoliosis/kyphosis, and variants on brain MRI. Developmental delays and cognitive impairment are universally present. The purpose of this study was to more fully describe tetrasomy 18p at both the genotypic and the phenotypic levels. Array CGH was performed on 43 samples from individuals with tetrasomy 18p diagnosed via routine karyotype. The medical records of 42 of these 43 individuals were reviewed. In order to gain additional phenotypic data, 31 individuals with tetrasomy 18p underwent a series of clinical evaluations at the Chromosome 18 Clinical Research Center. Results from the molecular analysis indicated that 42 of 43 samples analyzed had 4 copies of the entire p arm of chromosome 18; one individual was also trisomic for a section of proximal 18q. The results of the medical records review and clinical evaluations expand the phenotypic description of tetrasomy 18p to include neonatal jaundice and respiratory distress; recurrent otitis media; hearing loss; seizures; refractive errors; constipation and gastroesophageal reflux; cryptorchidism; heart defects; and foot anomalies. Additional findings identified in a small number of individuals include hernias, myelomeningocele, kidney defects, short stature, and failure to respond to growth hormone stimulation testing. Additionally, a profile of dysmorphic features is described. Lastly, a series of clinical evaluations to be considered for individuals with tetrasomy 18p is suggested.

Research-supported differential diagnosis of specific learning disabilities

Publisher Summary This chapter discusses research-generated inclusionary criteria for defining dyslexia in children and adults. Writing disabilities, in particular, are under-diagnosed and under-treated and may be an unrecognized contributor to academic failure and school drop-out rates. The International Dyslexia Association (IDA) defines dyslexia as a specific learning disability characterized by unexpected difficulty in accuracy and rate of decoding, word reading and text reading, and spelling. Exclusionary criteria prevent confusion of dyslexia with reading problems having other biological causes. The University of Washington (UW) research team conducted confirmatory factor analyses to evaluate the measurement model based on latent traits underlying multiple indicators or measures of the same process. Current school assessment practices focus on making educational decisions about whether children qualify for special education services rather than on making differential diagnoses. Insufficient attention is given to etiology of reading problems, linking assessment to research-supported effective instruction, and prognosis for long-range outcomes.

Improving student comfort with death and dying discussions through facilitated family encounters.

ObjectiveThe purpose of this study was to explore the educational potential for a collaboration between palliative medicine and psychiatry designed to improve first-year medical students’ knowledge and comfort with end-of-life issues through a facilitated small-group discussion with family members of recently-deceased loved ones.MethodsA group of 222 first-year medical students were divided into 14 small groups. Each group also consisted of two mental-health providers, one palliative-medicine interdisciplinary team member, and one family member of a recently-deceased hospice patient. A death- and- dying discussion between students and family members was facilitated by the mental-health and palliative-medicine faculty and was followed by post-activity evaluations.ResultsAs a result of the facilitated activity, 77% of participants reported increased comfort levels and 85% reported improved knowledge of end-of-life issues. Students reporting benefit were more likely to perceive higher facilitator and family comfort levels with end-of-life discussions, better activity organization, and utility of post-encounter group discussion.ConclusionFacilitated conversations between students and family members of recently-deceased loved ones may improve comfort and knowledge with end-of-life conversations. Future studies should explore the longer-range impact of this educational activity.

Establishing a reference group for distal 18q-: Clinical description and molecular basis

Abstract Although constitutional chromosome abnormalities have been recognized since the 1960s, clinical characterization and development of treatment options have been hampered by their obvious genetic complexity and relative rarity. Additionally, deletions of 18q are particularly heterogeneous, with no two people having the same breakpoints. We identified 16 individuals with deletions that, despite unique breakpoints, encompass the same set of genes within a 17.6-Mb region. This group represents the most genotypically similar group yet identified with distal 18q deletions. As the deletion is of average size when compared with other 18q deletions, this group can serve as a reference point for the clinical and molecular description of this condition. We performed a thorough medical record review as well as a series of clinical evaluations on 14 of the 16 individuals. Common functional findings included developmental delays, hypotonia, growth hormone deficiency, and hearing loss. Structural anomalies included foot anomalies, ear canal atresia/stenosis, and hypospadias. The majority of individuals performed within the low normal range of cognitive ability but had more serious deficits in adaptive abilities. Of interest, the hemizygous region contains 38 known genes, 26 of which are sufficiently understood to tentatively determine dosage sensitivity. Published data suggest that 20 are unlikely to cause an abnormal phenotype in the hemizygous state and five are likely to be dosage sensitive: TNX3, NETO1, ZNF407, TSHZ1, and NFATC. A sixth gene, ATP9B, may be conditionally dosage sensitive. Not all distal 18q- phenotypes can be attributed to these six genes; however, this is an important advance in the molecular characterization of 18q deletions.

A review of 18p deletions

Since 18p‐ was first described in 1963, much progress has been made in our understanding of this classic deletion condition. We have been able to establish a fairly complete picture of the phenotype when the deletion breakpoint occurs at the centromere, and we are working to establish the phenotypic effects when each gene on 18p is hemizygous. Our aim is to provide genotype‐specific anticipatory guidance and recommendations to families with an 18p‐ diagnosis. In addition, establishing the molecular underpinnings of the condition will potentially suggest targets for molecular treatments. Thus, the next step is to establish the precise effects of specific gene deletions. As we look forward to deepening our understanding of 18p‐, our focus will continue to be on the establishment of robust genotype–phenotype correlations and the penetrance of these phenotypes. We will continue to follow our 18p‐ cohort closely as they age to determine the presence or absence of some of these diagnoses, including spinocerebellar ataxia (SCA), facioscapulohumeral muscular dystrophy (FSHD), and dystonia. We will also continue to refine the critical regions for other phenotypes as we enroll additional (hopefully informative) participants into the research study and as the mechanisms of the genes in these regions are elucidated. Mouse models will also be developed to further our understanding of the effects of hemizygosity as well as to serve as models for treatment development.

Congruence of Test-Behavior Dimensions among Child Groups that Vary in Gender, Race-Ethnicity, and Ses

The possibility of construct bias was investigated with the Guide to the Assessment of Test Session Behavior for the WISC-III and WIAT (GATSB). Specifically, the study examined whether the three constructs measured by the GATSB (i.e., Avoidance, Inattentiveness, and Uncooperative Mood) share the same factor structure across demographic groups that vary in gender, race-ethnicity (Anglo, African-American, Hispanic), and SES (high, middle, low). Children (N = 969) ranged between the ages of 6 and 16 years and comprised the GATSBs standardization and validity-study samples. Coefficients of factorial congruence/similarity were sufficiently high to warrant the conclusion that the GATSBs three constructs are comparable (i.e., share the same factor structure) for children who differ by gender, race-ethnicity, and SES. The current findings align with previous bias studies conducted with the GATSB (Glutting, Oakland, & Konold, 1994; Nandakumar, Glutting, & Oakland, 1993) and indicate that Anglo examiners can place considerable confidence in using this instrument to measure the test-taking behaviors of children who differ by gender and SES as well as those who are Anglo, African-American, and Hispanic.

Consequences of chromsome18q deletions

Providing clinically relevant prognoses and treatment information for people with a chromsome18q deletion is particularly challenging because every unrelated person has a unique region of hemizygosity. The hemizygous region can involve almost any region of 18q including between 1 and 101 genes (30 Mb of DNA). Most individuals have terminal deletions, but in our cohort of over 350 individuals 23% have interstitial deletions. Because of this heterogeneity, we take a gene by gene approach to understanding the clinical consequences. There are 196 genes on 18q. We classified 133 of them as dosage insensitive, 15 (8%) as dosage sensitive leading to haploinsufficiency while another 10 (5%) have effects that are conditionally haploinsufficient and are dependent on another factor, genetic or environmental in order to cause an abnormal phenotype. Thirty‐seven genes (19%) have insufficient information to classify their dosage effect. Phenotypes attributed to single genes include: congenital heart disease, minor bone morphology changes, central nervous system dysmyelination, expressive speech delay, vesicouretreral reflux, polyposis, Pitt‐Hopkins syndrome, intellectual disability, executive function impairment, male infertility, aural atresia, and high frequency sensorineural hearing loss. Additionally, identified critical regions for other phenotypes include: adolescent idiopathic scoliosis and pectus excavatum, Virchow‐Robin perivascular spaces, small corpus callosum, strabismus, atopic disorders, mood disorder, IgA deficiency, nystagmus, congenital heart disease, kidney malformation, vertical talus, CNS dysmyelination growth hormone deficiency and cleft palate. Together these findings make it increasingly feasible to compile an individualized syndrome description based on each persons individuated genotype. Future work will focus on understanding molecular mechanisms leading to treatment.