Total IQ Scores Research Articles

Dp71 and intellectual disability in Indonesian patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscular disease marked by developmental delays due to mutations in the DMD gene, which encodes dystrophin. Brain comorbidity adds to the burden of limited mobility and significantly impacts patients' quality of life and their family. The changes of expression of dystrophin isoforms in the brain due to DMD gene mutations are thought to be related to the cognitive and neurobehavior profiles of DMD. This cross-sectional study aimed to characterize cognitive and neurodevelopmental profiles of patients with DMD and to explore underlying genotype-phenotype associations. Patients with DMD aged 5-18 years from Dr Sardjito Hospital and Universitas Gadjah Mada Academic Hospital from 2017-2022 were included. Multiplex ligation-dependent probe amplification and whole exome sequencing were used to determine mutations in the DMD genes. Cognitive function was measured by intelligence quotient testing using the Wechsler Intelligence Scale for Children and adaptive function tests with Vineland Adaptive Behavior Scales. The Autism Mental Status Exam and Abbreviated Conner's Rating Scale were used to screen for autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD), respectively. The mean total IQ score of DMD patients was lower than that of the general population (80.6 ± 22.0 vs 100 ± 15), with intellectual disability observed in 15 boys (29.4%). Of the 51 patients with DMD, the Dp71 group had the lowest cognitive performance with a total IQ score (46 ± 24.8; p = 0.003), while the Dp427 group and Dp140 group's total IQ scores were 83.0 ± 24.6 and 84.2 ± 17.5 respectively. There were no DMD patients with ASD, while 4 boys (7.8%) had comorbidity with ADHD. Boys with DMD are at higher risk of intellectual disability. The risk appears to increase with mutations at the 3' end of the gene (Dp71 disruption). Moreover, Dp71 disruption might not be associated with ADHD and ASD in patients with DMD.

Impact of PICU Admission on Neurocognitive Function in Children

Abstract Objective To study the impact of admission to a pediatric intensive care unit (PICU) on children's neurocognitive performance. Methods A case–control observational study including 50 children & adolescents and 75 age and gender matched children and adolescents.The study subjects underwent formative IQ testing using the Stanford Binet IQ test 3 months after discharge from the PICU. Results 27 males and 23 females with a mean age of 6.98 years were included in the study. Almost two thirds of the cases were admitted to the PICU post operatively (surgical causes). More than half of the cases needed sedation, 38% needed mechanical ventilation and 12% needed inotropic support. There was no statistically significant difference between cases and controls are regard IQ scores (total, verbal and performance IQ scores), neither was there a difference between medical and surgical cases. Data from similar pediatric cohorts is conflicting. Conclusion PICU does not seem to affect cognitive outcome in pediatric survivors. Further long term studies using standard scoring systems and time points of assessment are required.

NEUROPSYCHOMOTOR DEVELOPMENT IN CHILDREN AND ADOLESCENTS WITH LIVER DISEASES: SYSTEMATIC REVIEW WITH META-ANALYSIS

The nature of liver disease, the evolutionary course and duration of liver diseases, as well as the degree of severity and disability can trigger multiple outcomes with repercussions on neuromotor acquisition and development. To systematically review and conduct a meta-analysis to evaluate the effects of liver disease on the neuropsychomotor development of children and adolescents with their native livers and those who underwent liver transplantation. Observational studies published since the early 1980s until June 2019 were sought in the PubMed and Scopus databases. An α value of 0.05 was considered significant. The statistical heterogeneity of the treatment effect between the studies was assessed by the Cochran's Q test and the I2 inconsistency test, in which values above 25 and 50% were considered indicative of moderate and high heterogeneity, respectively. Analyses were performed with Review Manager 5.3. Twenty-five studies met the eligibility criteria, including 909 children and adolescents with liver disease. Meta-analyses showed deficits in total IQ -0.41 (95%CI: -0.51 to -0.32; N: 9,973), verbal IQ -0.38 (95%CI: -0.57 to -0.18; N: 10,284) and receptive language -0.85 (95%CI: -1.16 to -0.53; N: 921) in liver transplantation, and those with native livers who had symptoms early had total and verbal IQ scores (85±8.8; 86.3±10.6 respectively) lower than the scores of those with late manifestations (99.5±13.8; 96.2±9.2). Gross motor skill was reduced -46.29 (95%CI: -81.55 to -11.03; N: 3,746). Acute or chronic liver disease can cause declines in cognitive, motor and language functions. Although the scores improve after liver transplantation, children remain below average when compared to healthy children.

Brain malformations and cognitive performance in spina bifida.

To systematically characterize radiological features of patients with spina bifida, their relationship to cognitive function, and differences between spina bifida aperta (SBA) and spina bifida occulta (SBO). In a retrospective study of 265 patients (117 females, 148 males; median age at imaging 11y, range 1-47y; SBA n=206, SBO n=59), the radiological phenotype was assessed through magnetic resonance imaging (MRI) (SBA n=171, SBO n=59). In 126 patients (SBA n=116, SBO n=10) Kaufman Assessment Battery for Children (KABC) or Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) and Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) were performed. Patients with spina bifida show numerous brain malformations, always present for SBA but rarely for SBO. The most frequent brain malformations in SBA included abnormal corpus callosum (69%), hypoplastic pons (50%), and hypoplastic mesencephalon (20%). Cognitive total IQ scores were below average in 44% (KABC) to 49% (WISC-IV) of children with SBA, while almost all children with SBO scored at least average. Stenogyria (p=0.006), pons (p=0.003), and mesencephalon hypoplasia (p=0.01) correlated with lower total IQ score and verbal comprehension. Various brain malformations correlate significantly with several cognitive domains, while lesion level only correlates with processing speed. IQ scores were significantly lower in patients with SBA than in patients with SBO. Verbal competence, perceptual reasoning, and working memory were significantly impaired for SBA and correlated with stenogyria and abnormalities of the midbrain and corpus callosum. Brain malformations occur more frequently in spina bifida aperta (SBA) than in spina bifida occulta (SBO). Cognitive impairment is less frequent in SBO. Hydrocephalus, stenogyria, midbrain, and corpus callosum abnormalities are associated with lower cognitive function. Difference in prognosis in SBO versus SBA can alter prenatal counselling.

Comparison of cognitive function, socioeconomic level, and the health-related quality of life between epileptic patients with attention deficit hyperactivity disorder and without

BackgroundEpilepsy is one of the most common neurological conditions. Attention deficit hyperactivity disorder (ADHD) in children with epilepsy proves to be very common. Both epilepsy and ADHD impair quality of life. We aimed to evaluate cognitive function, socioeconomic level, and quality of life (QOL) among children with ADHD and epilepsy. A total of 100 children were divided into 5 groups (20 children/group) as (I) epilepsy, (II) ADHD with epilepsy, (III) ADHD with EEG changes, (IV) ADHD without EEG changes, and (V) control. Children aged between 6 and 11 years were recruited for this study. Early Childhood Epilepsy Severity Scale (E-Chess), Conners’ Parent Rating Scale (CPRS), Wechsler Intelligence Scale for Children-3rd edition (WISC-III), socioeconomic scale for assessment of social burden and socioeconomic classes, and PedsQL (quality of life measure) assessed.ResultsChildren with ADHD and epilepsy had the lowest PedsQL total scores and lower scores than other groups especially in performance IQ score. The highest percentage of low socioeconomic class (25%) was observed in the group of ADHD with epilepsy and the group of epilepsy.ConclusionADHD with epilepsy is associated with low performance IQ, poor socioeconomic level, and quality of life. Pediatric Quality of Life Inventory scores show significant correlation with total IQ score in the group of ADHD with epilepsy.

Similarities and differences in psycho-educational assessments of adolescents with specific language impairments and specific learning disabilities: A challenging differential diagnosis.

Specific Language Impairment (SLI) and Specific Learning Disabilities (SLD) have been the subject of extensive research especially with respect to the connection between them. However, the manifestation of these disorders in adolescence has not been thoroughly investigated. The objective of the present study was to compare the intelligence scores and the reading, oral and written language skills of Greek adolescents with SLI and Greek adolescents with SLD, as assessed during their psycho-educational evaluation, in order to clear the path for diagnosis and intervention. 124 Greek adolescents diagnosed with Specific Learning Disabilities and 76 Greek adolescents diagnosed with Specific Language Impairment aged from 11 to 16 years took part in the study. All participants were assessed in reading, oral language and written language skills and took part in IQ testing. Independent samples t-test, chi-square test, odds ratios and their 95 percent confidence intervals were implemented to determine statistically significant differences. Analyses revealed differences in IQ scores and some differences in the skills assessed, thus indicating that SLI adolescents exhibited more difficulties across most of the basic academic skills, whereas SLD adolescents' difficulties confined to the affected written language skills. Specifically, the observed difference was statistically significant for the total and verbal IQ score, and WISC-III scores also disclosed a significant difference for the similarities and information defisub- tests. Regarding reading skills, SLI adolescents were 4.9 times more likely to exhibit line skipping, 5.8 times more likely to exhibit hesitations, 3.2 times more likely to exhibit repetitions of syllables/words/ phrases, and 8.5 times more likely to exhibit non-acknowledgement of punctuation. Regarding reading comprehension, adolescents with SLI were more likely to have difficulty in retrieving simple information questions, making inferences, and giving titles. Adolescents with SLI were also more likely to have difficulties in story reproduction, giving synonyms/opposites, oral sentence reproduction and auditory oral word reproduction. In the area of written language skills, SLI adolescents were more likely to have poor handwriting, poor content, poor structure, and poor use of punctuation. In adolescence, Specific Language Impairment can be a different manifestation of an ongoing language disorder, which finally appears as a different type of Specific Learning Disability, but with a more generalized nature of learning difficulties. This finding should be interpreted in terms of the importance of differential diagnosis, especially during the challenging period of adolescence.

Anxiety disorders in children with high intellectual potential.

Several studies have reported anxiety disorders in children with high intellectual potential (HIP). However, there are discrepant results possibly as a result of methodological biases (different/absent definitions of HIP, small sample sizes, non-validated/adapted/specific tools for assessing anxiety and a single observational source). To examine more thoroughly the relationships between HIP and anxiety in large samples of children using clear definitions of HIP, different observational sources and specific assessments of anxiety. Children with HIP (n = 211, total IQ ≥130) were compared with children without HIP (n = 397, total IQ <130) for anxiety using different observational sources (child psychiatric diagnosis, parental evaluation and child's self-evaluation). Intellectual functioning was assessed using the Wechsler Intelligence Scale. There were significantly more children with HIP who had anxiety disorders than children without HIP based on the child psychiatric diagnosis. Moreover, based on the child's self-evaluation, children with a high Verbal Comprehension Index (VCI ≥130) were significantly more anxious than children with a VCI <130, whereas children with a high Perceptual Reasoning Index (PRI ≥130) were significantly less anxious than children with a PRI <130. Finally, there was no significant relationship between levels of intellectual functioning and anxiety according to parental observation. The results highlight the importance of using multiple observational sources and conducting analyses on different dimensions of intellectual functioning (such as VCI and PRI), rather than only on the composite total IQ score. High verbal potential might be a factor of vulnerability for anxiety, whereas high perceptual reasoning might be a protective factor. Further studies are necessary to understand better the mechanisms underlying these results.

EFFECTS OF INTELLIGENCE AND MEMORY ON NEUROPSYCHOLOGICAL RESPONSES IN POLYGRAPH TESTING

The polygraph is widely used to detect concealed information or deception; however, whether examinees’ intelligence and memory quotients would influence the psychophysiological responses, and thus the effectiveness of the polygraph, has rarely been studied systematically. The present study investigated this issue by using a polygraph on 82 participants with intelligence or memory impairments in a Concealed Information Test (CIT). The Wechsler Adult Intelligence Scale and the Wechsler Memory Scale were used to measure participants’ intelligence and memory quotients. Analysis showed that participants’ total IQ score and their scores on subtests, including information, comprehension, similarities, arithmetic, digit-symbol coding, and block design, were positively correlated with skin conductance response and the detect accuracy of the polygraph test. Participants who were tested inaccurately had significantly lower IQ scores than those who were tested accurately. In contrast, no significant correlation was found between MQ and polygraph test accuracy; however, further research is needed to investigate this issue, considering the floor effect of the Wechsler Memory Scale. The present study is not only beneficial for utilizing polygraph more scientifically, but also for expanding its application on people with cognitive impairments.

Effect of treatment on cognitive and attention problems in children with narcolepsy type 1.

To ascertain the presence of cognitive and attention problems in treatment naïve children with narcolepsy type 1 (NT1) and to explore whether children recently diagnosed with NT1 improve with respect to cognition and attention problems 1 year after regular treatment for NT1. A total of 15 treatment naïve children (7-15 years) with recently diagnosed NT1 were recruited from three sleep medicine centers in the Netherlands. The control group consisted of 15 healthy children, being frequency matched on age and gender. Both groups were investigated at baseline to examine intelligence profile (Wechsler Intelligence Scale for Children [WISC] III), attention problems, and processing speed (Bourdon Vos and sustained attention to respond task [SART]). These tests were repeated in children with NT1 1 year after regular (behavioral and medication) treatment for NT1. Children with NT1 scored significantly lower on the verbal scale and processing speed subscale of the WISC III, showed more fluctuations in reaction time of the Bourdon Vos and made more mistakes during the SART than the healthy control group at baseline. Children with NT1 significantly improved on total IQ score, and on the WISC indices processing speed, and perceptual organization 1 year after treatment. At follow-up, test scores of treated children were largely comparable to those of the control group at baseline. Children with NT1 show improvement in several cognitive domains 1 year after start of treatment. Our findings stress the need for early detection and treatment of narcolepsy in childhood.

Assessment of upper airway obstruction in children with specific learning disorder

Aim: A growing number of findings suggest that there is an important relationship between upper airway obstruction (UAO) and specific learning disorder (SLD). However, existing evidence is limited to very few studies. We, thus, aimed to explore chronic UAO conditions in children with specific learning disabilities.Materials and Methods: This study involved seventy-seven children aged 7 to 10 years with SLD and eighty-six healthy children matching in age and gender. Psychiatric disorders were diagnosed through the Diagnostic and Statistical Manual of Mental Disorders (DMS-5) Criteria. Porteus Maze Test and Kent-EGY test were used to assess the intelligence of the participants. The diagnoses of UAO were made by a physical examination, a detailed otorhinolaryngologic examination, the anamnesis and clinical history, anterior rhinoscopy, and flexible endoscopic nasopharyngoscopy according to the type of UAO.Results: The rates of having at least one pathology causing UAO and secondary sleep difficulties due to UAO were significantly higher in children with SLD compared to controls. The severity of SLD was significantly associated with the severity of UAO and the presence of secondary sleep difficulties, but not the presence of UAO. The verbal and total IQ scores were significantly affected by the presence and severity of UAO, while the presence of secondary sleep difficulties significantly impacted all IQ scores.Conclusion: Parents, teachers, otorhinolaryngologists, child psychiatrists, and pediatricians should be aware that the association between learning disorders and UAO. It also would be advisable to screen children with learning disorders in terms of UAO, and vice versa.

Cognitive Functions in Breastfed versus Artificially Fed in Preschool Children

Background: Breastfeeding has been widely researched and reviewed in relation to cognitive performance in children, but early reviews have not provided compelling evidence linking breastfeeding to cognitive development Objective: To assess the effect of breastfeeding duration and exclusivity on the cognitive development of a group of preschool Egyptian children. Methods: The current study was a cross sectional comparative study that included 90 apparently healthy preschool Egyptian children aged 3 - <6 years who were classified into three equal groups according to their type of feeding in early infancy. Assessment of neurocognitive function and IQ was done using the following 3 tests: Stanford-Binet test 5th edition Arabic version (2003), Kaufman Assessment Battery for Children (2004), Illinois Test of Psycholinguistic Abilities (ITPA) (2001). Results: There was significant increase in IQ detected by kauffaman test in breastfed group than either mixed or artificially fed, while no significant difference was found in IQ between mixed and artificial fed groups. There was significant increase in psycholinguistic age in breastfed group in comparison to artificially fed groups, while no significant difference was found between breastfed and mixed fed or mixed fed and artificially fed groups. Children who were breastfed had better scores in Total IQ than either artificially or mixed fed. Also, there was significant increase in total IQ scores in mixed than artificially fed groups. A significant positive relation was found between the total duration of breastfeeding and Binet total IQ score. Conclusion: The effect of breastfeeding is dose-dependent, the longer the duration of breastfeeding, the more is the benefit, the strongest effect for cognitive function in breastfed children was more prominent in psycholinguistic age.

Multi-media biomarkers

OPS 03: Machine learning in environmental epidemiology, Room 315, Floor 3, August 26, 2019, 4:30 PM - 5:30 PM Background/Aim: Exposure assessment traditionally relies on measured chemical concentrations in a single biological medium. Toxicokinetic properties cause chemicals to distribute unevenly among different media, thus each medium provides incomplete information about body burden. We propose that machine learning and statistical approaches developed for mixtures can create aggregated exposure estimates, which we term multi-media biomarkers (MMBs), for a given chemical that outperform exposure estimates from individual media. Methods: We measured lead (Pb) in blood, hair, nails, and urine to derive aggregated MMBs and then tested their association with Wechsler Intelligence Scale for Children (WISC) total IQ scores in the Public Health Impact of Metals Exposure (PHIME) project, a study of Italian adolescents aged 10-14 years (N~720). We used a supervised learning technique, weighted quantile sum regression (WQS), and an unsupervised learning technique, independent component analysis (ICA) to create the Pb MMB. Since the MMB produced using ICA is not normally distributed, we measured adjusted associations between Pb and IQ using Spearman correlation and residuals generated from a model where sex and age are predictors of IQ. Results: Total IQ was associated with the Pb MMB for ICA (r=-0.14; p=0.03) and for WQS (r=-0.16; p=0.01). Total IQ was not associated with Pb measured using the individual exposure biomarkers (blood: r=-0.10; p=0.11, urine: r=0.09; p=0.13, hair: r=-0.10; p=0.11, nails: r=-0.06; p=0.35). Weights highlighting the contributions to each MMB indicate that nails (59%) and hair (23%) contributed most for WQS, whereas blood (51%) and nails (21%) contributed most for ICA. Conclusions: These results indicate that MMBs can be more effective measures of exposure than individual biomarkers. Though MMBs have increased assay costs, they may increase statistical power when the choice of exposure medium is unclear. Future work will need to validate these methods for other toxicants and evaluate the associations with WISC subscales.

Comparison of CNS Relapse, Survival and Intelligent Quotient in Non-High Risk ALL Children Treated with Intrathecal Methotrexate or Triple Intrathecal Therapy

Background Compared to intrathecal methotrexate (IT MTX), triple intrathecal therapy (TIT) has shown promising results in decreasing central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL). We aimed to compare these two IT regimens in terms of CNS relapse, survival, and IQ in Iranian non-high risk ALL children. Materials and Methods In a two phases clinical trial study, 203 children with non-high risk ALL, aged 1-10 years at diagnosis, who were previously treated with the same systemic protocol but with two different IT regimens, based on IT regimen allocated to IT MTX (n = 109) and TIT (n = 84) groups were studied. In phase 1, isolated CNS relapses (i-CNS) and five-year survival of the two groups was compared, and in phase 2, IQ score of survivors of two groups was measured and compared. Results The overall rate of i-CNS relapse was 13.8% and the incidence of i-CNS relapse in contrast to other areas in the IT MTX group, was higher than in the TIT group (17.4% vs. 9.6%; P= 0.03). Most i-CNS relapses were asymptomatic and early and there was no significant relation between IT formulation and secondary relapse and mortality rate in patients with i-CNS relapse (P> 0.05). The 5-year survival of TIT group was more than the IT MTX group (80.9% vs.70.6%; P=0.04), but the mean scores of full-scale, verbal, and performance IQ (except cubes) were not significantly different in the two groups. Conclusion Based on the results, TIT regimen compared to IT MTX reduced i-CNS relapse and increased 5-year survival in Iranian children with ALL but had no significant differences in total IQ score.

An exploration of the association between matrix reasoning and eating disturbance behavior in girls with autism spectrum disorder.

BackgroundAlthough there have been suggestions that central coherence may be associated with eating disturbances (EBD) in children with autism spectrum disorder (ASD), relatively little attention has been given to specific aspects of IQ and EDB.MethodsThe association between total IQ, perceptual and verbal composite scores and subtests was explored in a sample of 50 high-functioning girls with ASD (mean age = 9.7 years, SD = 2.4 years, range = 6 years to 14 years). Self-reports and mothers’ reports were collected about the girls’ EDB.ResultsThere were only isolated associations between mothers’ data and the girls’ IQ. Selected aspects of the girls’ self-reported EDB were significantly associated with matrix reasoning.ConclusionThe role of IQ, particularly matrix reasoning, in the assessment and treatment of EDB in girls with ASD, is highlighted by these findings.

The Predictive Value of Amplitude-Integrated Electroencephalography in Preterm Infants for IQ and Other Neuropsychological Outcomes at Early School Age

Background: Amplitude-integrated electroencephalography (aEEG) is used increasingly in neonatal intensive care and seems helpful in predicting outcomes at the age of 2 years. Objectives: To determine whether early aEEG patterns in preterm infants are equally useful in predicting outcomes at early school age. Methods: We recorded aEEG in 41 preterms (gestational age 26.0–32.9 weeks) at a median postnatal age of 9.7 h (IQR 7.0–25.3) and in 43 preterms on median day 8 (IQR 7–9). We assessed aEEG by pattern recognition and calculated the means of the aEEG amplitude centiles. At a median of 7.39 years, i.e., early school age, we assessed their motor, cognitive, and behavioral outcomes. Results: Depressed aEEG patterns were not associated with poorer outcomes. Cyclicity directly after birth was associated with a higher total IQ (mean 104 vs. 97, p = 0.05) and higher scores on visual perception (mean percentile 57.1 vs. 40.1, p = 0.049) and visual memory (mean percentile 34.5 vs. 19.1, p = 0.090). We found some associations between the aEEG amplitude centiles and cognitive outcomes, but none for motor or behavioral outcomes. There was an increased risk of abnormal scores on long-term verbal memory in cases of the lower 5th and 50th aEEG amplitude centiles directly after birth. The odds ratios were 0.65 (95% CI 0.42–0.99, p = 0.040) and 0.71 (95% CI 0.52–0.96, p = 0.025), respectively. Conclusions: In relatively healthy preterm infants the value of aEEG in predicting neuropsychological outcomes at early school age is limited. The presence of cyclicity directly after birth tends to be associated with better cognition.

Regional brain tissue changes and associations with disease severity in children with sleep-disordered breathing.

Children with sleep-disordered breathing (SDB) exhibit behavioral, cognitive, and autonomic deficits, suggestive of neural injury. We assessed whether the tissue alterations resulted from acute or chronic processes, and whether alterations correlated with disease severity. Brain tissue integrity was examined with mean diffusivity (MD) (3.0 T scanner) in 20 nonsnoring controls (mean age ± SEM, 12.2 ± 0.6 years; 10 males) and 18 children with SDB (12.3 ± 0.7 years; 11 males). Sleep, cognitive, and behavioral measures were compared between groups following overnight polysomnography using Student's t tests. Whole-brain MD maps were realigned and averaged, normalized, smoothed, and compared between groups using ANCOVA (covariates: age, gender, and socioeconomic status). Partial correlations were calculated between whole-brain smoothed MD maps and obstructive apnea-hypopnea indices (OAHIs). Age, gender, and sleep variables did not differ between groups. The SDB group showed higher OAHIs, body mass indices, and systolic blood pressure. Significantly reduced MD values (acute changes) appeared in the hippocampus, insula, thalamus, temporal and occipital cortices, and cerebellum, but were increased (chronic damage) in the frontal and prefrontal cortices in the SDB group over controls. Both positive and negative correlations appeared with extent of tissue changes and disease severity. Externalizing and Total Problem Behaviors were significantly higher in children with SDB. Verbal, performance, and total IQ scores trended lower, and behavioral scores trended higher. Pediatric SDB is accompanied by predominantly acute brain changes in areas that regulate autonomic, cognitive, and mood functions, and chronic changes in frontal cortices essential for behavioral control. Interventions need to be keyed to address acute vs chronic injury.

Association between a functional interleukin 6 receptor genetic variant and risk of depression and psychosis in a population-based birth cohort

ObjectiveInterleukin 6 (IL-6) levels are commonly elevated in patients with depression and psychosis and in people who are at risk of developing these disorders. A common, functional variant in the IL6R gene (IL6R Asp358Ala; rs2228145 A > C) is known to dampen down inflammation by impairing IL6R signaling. We have examined the association of Asp358Ala with diagnosis of depression and psychosis, serum IL-6, CRP levels, and a number of risk factors commonly linked with inflammation, depression or psychosis. We predicted that if IL-6 were related to depression/psychosis risk causally, rather than due to confounding, Asp358Ala would be associated with risk of these disorders, serum IL-6, CRP levels, but not with any of the confounders. MethodWe used data from the population-based ALSPAC birth cohort. Serum IL-6 and CRP levels were measured at age 9 years. Psychotic disorder, ICD-10 diagnosis of severe depressive episode, and total depression score were assessed at age 18 years. IL6R Asp358Ala was genotyped using the Illumina HumanHap550 quad genome-wide SNP genotyping platform. Risk factors assessed include sex, body mass index, social class, ethnicity, maternal education, birth weight, gestational age, maternal post-natal depression, childhood psychological and behavioral problems, and total IQ score. ResultsAsp358Ala was associated with decreased risk of severe depression and/or psychosis; adjusted odds ratio for those with CC, compared with AA, genotype was 0.38 (95% CI, 0.15–0.94). The variant was associated with increased serum IL-6 levels (P = 5.5 × 10−22) but decreased serum CRP levels (P = 3.5 × 10−5), consistent with an anti-inflammatory effect downstream of IL-6. Asp358Ala was not associated with total depression score. Asp358Ala was not associated with any of the other risk factors commonly linked with inflammation, depression or psychosis (all P > 0.20). ConclusionsThe findings provide further evidence that the IL-6/IL6R pathways are involved in pathogenesis of severe depression and psychosis, and may be novel therapeutic targets. Previously reported associations between IL-6, depression and psychosis are unlikely to be fully explained by confounding. Based on a small number of cases, findings from the current study need replication in other samples.

Humans Chromosome 1 Fractal periods signature is highly correlated with Intelligence and Brain Evolution

Abstract DUF1220 proteins regions show the largest Homo-Sapiens lineage-specific increase in copy number of any protein-coding region in the human genome and map principally to 1q21.1. DUF1220 deletions have been associated with microcephaly and macrocephaly, respectively. DUF1220 copy number has been linked to both brain size in humans and brain evolution among primates. Remarkably, dosage variations involving DUF1220 sequences have now been linked to human brain expansion, autism severity, total IQ, and cognitive and mathematical aptitude scores. We analyzed in chromosome 1q a total of 245 DUF1220 proteins. Finally the method is extended analysing the long 1q21 region from 7 other close primates like Neanderthal, great apes : chimp, gorilla, orangutan and monkeys : macaque, marmoset, vervet. This remarkable property is confirmed by comparing these primates to other mammals such as mice, rabbit, cow, dolphin and Elephant. We then show four classes of multi-periodic fractal structures for all 19 DUF1220 regions and 19 NBPF genes studied cases. The analysis of these spectra of fractal periods1 reveals a simple linear interdependence, hierarchization and unification between the numerical sequences of each of these 4 spectra and the sequences of Fibonacci and Lucas. Given the evidence of this numerical relationship, we suggest that this discovery may be one of the major causes of a cognitive development of man superior to that of the great primates. Finally the mathematical roots of this whole numbers resonance patterns is discussed.

Effect of Intrathecal Methotrexate Injectionon Neurocognitive Functions in Children with Non Hodgkin Lymphoma after Treatment

Introduction and aim of work: Neurocognitive late effects are common sequelae of cancer in children, especially in those who have undergone treatment for brain tumors or in those receiving prophylactic cranial radiation or intrathecal chemotherapy therapy to treat leukemia and non Hodgkin lymphoma (NHL). As NHL represents 8–10% of all malignancies in children between 5–19 years of age (Cairo, 2009) and all NHL children receive intrathecal methotrexate as therapy or prophylaxis so we studied effect of intrathecal methotrexate in NHL treated children in their cognitive function and compare it with normal children, also we studied effect of some risk factors (age at disease onset and number of intrathecal injections) on the affected intelligence subscales and lastly a suitable and applicable model to evaluate neurocognitive function was done. Patients and methods: The study included 25 NHL treated children and 10 children as controls, all children are subjected to some specific neurocognitive tests and sheet for assessment of neurocognitive function as complementary study. Result: It showed that total IQ score, verbal and quantitative subscales are significantly affected in NHL patients and verbal subscale is more affected in children who began treatment at younger age

DUF1220 Homo Sapiens and Neanderthal fractal periods architectures breakthrough

DUF1220 proteins regions show the largest Homosapiens lineage-specific increase in copy number of any protein- coding region in the human genome and map principally to 1q21.1, and partially also in 1p. DUF1220 deletions and reciprocal duplications have been associated with microcephaly and macrocephaly, respectively. In Colorado University Dr Sikela team established that human genome sequences encoding DUF1220, show a dramatically elevated copy number in the human lineage and variation in DUF1220 copy number has been linked to both brain size in humans and brain evolution among primates. Remarkably, dosage variations involving DUF1220 sequences have now been linked to human brain expansion, autism severity, total IQ, and cognitive and mathematical aptitude scores. We analyzed in chromosome 1q a large region of 218 contiguous DUF1220 as well as in the chromosome 1p five other regions of DUF1220 smaller, then a total of 245 DUF1220 proteins. We supplemented by analyzing 16 RNAs of NBPF genes containing these DUF1220 and also 3 representative NBPF genes from Neanderthal genome. Finally the method is extended ananlysing the long 1q21 region from 7 other close primates like Neanderthal, great apes : chimp, gorilla, orangutan and monkeys : macaque, marmoset, vervet. This remarkable property is confirmed by comparing these primates to other mammals such as mice, rabbit, cow, dolphin and Elephant. We then show four classes of multi-periodic fractal structures for all 19 DUF1220 regions and 19 NBPF genes studied cases. The analysis of these spectra of fractal periods2 reveals a simple linear interdependence, hierarchization and unification between the numerical sequences of each of these 4 spectra and the sequences of Fibonacci and Lucas. Given the evidence of this numerical relationship, we suggest that this discovery may be one of the major causes of a cognitive development of man superior to that of the great primates