CNVs conferring risk of autism or schizophrenia affect cognition in controls.

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.

Long-term outcome of medically confirmed and self-reported early traumatic brain injury in two nationwide samples.

PRIMARY OBJECTIVES: To assess long-term effects of early traumatic brain injury (TBI) on mental health, cognition, behaviour and adjustment and to identify prognostic factors. METHODS AND PROCEDURES: A 1-year nationwide cohort of all 0-19 year old Icelandic children and adolescents diagnosed with TBI in 1992-1993 (n = 550) received a questionnaire with clinical outcome scales and questions on TBI and socio-economic status (SES) by mail ∼16 years post-injury. A control group (n = 1232), newly selected from the National Registry, received the same questionnaire. Non-respondents answered a shorter version by telephone. Overall participation was 67%. MAIN OUTCOMES AND RESULTS: Medically confirmed and self-reported TBI was reflected in worse outcome. Force of impact, number and severity of TBIs predicted poorer results. Parental SES and demographic factors had limited effects. Not reporting early, medically confirmed TBI did not exclude cognitive sequelae. In self-reported disability, absence of evaluation for compensation was not linked to outcome. CONCLUSIONS: Clinical outcome was consistent with late complaints attributed to early TBI. TBI-related variables had greater prognostic value than other factors. Self-reporting of TBI sustained very early in life needs supplementary information from parents and medical records. More consistency in compensation evaluations following paediatric TBI is indicated.

The scope of early traumatic brain injury as a long-term health concern in two nationwide samples: prevalence and prognostic factors.

PRIMARY OBJECTIVES: To examine the scope of paediatric traumatic brain injury (TBI) as a health concern and to identify prognostic factors for TBI-related sequelae. METHODS AND PROCEDURES: The study was prospective and nationwide. A questionnaire was sent to a study group (SG) of all 0-19 years old in Iceland, diagnosed ∼16 years earlier with TBI during a 1-year period, 1992-1993 (n = 550) and to a control group (CG) (n = 1232), selected from the National Register. MAIN OUTCOMES AND RESULTS: In the CG 49.5% reported having sustained TBI and 7.0% reported long-term disability. In the group with TBI, force of impact to the head, more than one incident of TBI and the injury severity by gender interaction predicted late symptoms. TBI severity had substantially less effect than force of impact and was close to non-existent for females. CONCLUSIONS: Based on two independent nationwide samples, the scope of TBI as a health concern in adolescence and young adulthood is greater than previously documented. The findings suggest that TBI event-related factors, especially force of impact, have greater predictive value than clinical symptoms of severity at the acute stage, females being more sensitive to the effects of mild TBI than males.

A sequence variant associating with educational attainment also affects childhood cognition.

Only a few common variants in the sequence of the genome have been shown to impact cognitive traits. Here we demonstrate that polygenic scores of educational attainment predict specific aspects of childhood cognition, as measured with IQ. Recently, three sequence variants were shown to associate with educational attainment, a confluence phenotype of genetic and environmental factors contributing to academic success. We show that one of these variants associating with educational attainment, rs4851266-T, also associates with Verbal IQ in dyslexic children (P = 4.3 × 10-4, ß = 0.16 s.d.). The effect of 0.16 s.d. corresponds to 1.4 IQ points for heterozygotes and 2.8 IQ points for homozygotes. We verified this association in independent samples consisting of adults (P = 8.3 × 10-5, ß = 0.12 s.d., combined P = 2.2 x 10-7, ß = 0.14 s.d.). Childhood cognition is unlikely to be affected by education attained later in life, and the variant explains a greater fraction of the variance in verbal IQ than in educational attainment (0.7% vs 0.12%,. P = 1.0 × 10-5).

The Adult Reading History Questionnaire (ARHQ) in Icelandic: Psychometric Properties and Factor Structure.

This article describes psychometric testing of an Icelandic adaptation of the Adult Reading History Questionnaire (ARHQ), designed to detect a history of reading difficulties indicative of dyslexia. Tested in a large and diverse sample of 2,187 adults, the Icelandic adaptation demonstrated internal consistency reliability (Cronbach's alpha = .92) and test-retest reliability (r = .93). Validity was established by comparing scores of adults who as children received ICD-10 diagnoses of specific reading disorder (F81.0; n = 419) to those of adults defined as nondyslexics (n = 679). ROC curve analysis resulted in an area under the curve of .92 (95% CI = .90, .93, p < .001) and a cutoff score of .43 with sensitivity of 84.5% and specificity of 83.7%. An exploratory factor analysis (n = 2,187) suggested three subscales, Dyslexia Symptoms, Current Reading, and Memory, the mean scores of which differed significantly among diagnosed dyslexics, relatives of dyslexics, and population controls. Our results support the applicability of the ARHQ in Icelandic as a self-report screening tool for adult dyslexia in Iceland.

The prognostic value of injury severity, location of event, and age at injury in pediatric traumatic head injuries.

AIMS: To estimate the prognostic value of injury severity, location of event, and demographic parameters, for symptoms of pediatric traumatic head injury (THI) 4 years later. METHODS: Data were collected prospectively from Reykjavik City Hospital on all patients age 0-19 years, diagnosed with THI (n = 408) during one year. Information was collected on patient demographics, location of traumatic event, cause of injury, injury severity, and ICD-9 diagnosis. Injury severity was estimated according to the Head Injury Severity Scale (HISS). Four years post-injury, a questionnaire on late symptoms attributed to the THI was sent. RESULTS: Symptoms reported were more common among patients with moderate/severe THI than among others (p < 0.001). The event location had prognostic value (p < 0.05). Overall, 72% of patients with moderate/severe motor vehicle-related THI reported symptoms. There was a curvilinear age effect (p < 0.05). Symptoms were least frequent in the youngest age group, 0-4 years, and most frequent in the age group 5-14 years. Gender and urban/rural residence were not significantly related to symptoms. CONCLUSIONS: Motor vehicle related moderate/severe THI resulted in a high rate of late symptoms. Location had a prognostic value. Patients with motor vehicle-related THI need special consideration regardless of injury severity.

Urban-rural differences in pediatric traumatic head injuries: A prospective nationwide study.

AIMS: To estimate differences in the incidence of recorded traumatic head injuries by gender, age, severity, and geographical area. METHODS: The study was prospective and nationwide. Data were collected from all hospitals, emergency units and healthcare centers in Iceland regarding all Icelandic children and adolescents 0-19 years old consecutively diagnosed with traumatic head injuries (N = 550) during a one-year period. RESULTS: Annual incidence of minimal, mild, moderate/severe, and fatal head injuries (ICD-9 850-854) was 6.41 per 1000, with 95% confidence interval (CI) 5.9, 7.0. Annual incidence of minimal head injuries (ICD-9 850) treated at emergency units was 4.65 (CI 4.2, 5.1) per 1000, mild head injuries admitted to hospital (ICD-9 850) was 1.50 (CI 1.3, 1.8) per 1000, and moderate/severe nonfatal injuries (ICD-9 851-854) was 0.21 (CI 0.1, 0.3) per 1000. Death rate was 0.05 (CI 0.0, 0.1) per 1000. Young children were at greater risk of sustaining minimal head injuries than older ones. Boys were at greater risk than girls were. In rural areas, incidence of recorded minimal head injuries was low. CONCLUSIONS: Use of nationwide estimate of the incidence of pediatric head injury shows important differences between urban and rural areas as well as between different age groups.

[Extremely Low Birthweight Infants in Iceland. Health and development.].

OBJECTIVE: Survival of extremely low birthweight infants (BW<1000g) in Iceland has increased in recent years, especially since the availability of surfactant therapy for Respiratory Distress Syndrome of Prematurity. This study was part of a geographically defined national study on survival, health, development and longterm outcome of extremely low birthweight (ELBW) infants in Iceland focusing on health, development and disabilities with reference to a control group. MATERIAL AND METHODS: Information from the National Birth Registry on births in Iceland of ELBW infants weighing 500-999g was collected in two periods 1982-90 and 1991-95, before and after surfactant therapy became available. Information on pregnancy, birth, diseases in the newborn period and later health problems was collected from hospital records. The ELBW infants born in 1991-95 and matched control children were enrolled to a prospective study on longterm health and development. The children undervent medical examinations and developmental testing at 5 years of age in 1996-2001. Comparison was made between the two groups of ELBW infants and between ELBW infants and control children born in 1991-95. RESULTS: In 1982-90 the longterm survival of ELBW infants at 5 years of age was 22% and 52% in 1991-95. In both periods 1982-90 and 1991-95 similar data was found on ELBW infants regarding mothers health, pregnancy, birth and neonatal period. Difference was found in maternal age being significantly higher (p=0.02) and significally more deliveries by cesarian section (p=0.02) in the latter period. The two groups of ELBW infants were similar regarding sex, birthweight and diseases in the newborn period. Comparison between 35 ELBW infants and 55 control children born 1991-95 showed that significantly more mothers of ELBW children smoked during pregnancy (p=0.003) and suffered from various diseases (p=0.001). More ELBW children were born by cesarian section (p=0.001) than control children and their parents reported more longterm health problems regarding astma (p=0.001), convulsions (p=0.001), difficulties in swallowing (p=0.001) and weight gaining (p=0.005). At five years of age significantly more ELBW children born in 1991-95 compared to control children had abnormal general physical examination (p