1. Bailey AR, Giunta BN, Obregon D, Nikolic WV, Tian J, Sanberg CD, Sutton DT, Tan J. {{Peripheral biomarkers in Autism: secreted amyloid precursor protein-alpha as a probable key player in early diagnosis}}. {Int J Clin Exp Med};2008;1(4):338-344.
Autism is a pervasive developmental disorder characterized by impairments in socialization and communication. There is currently no single molecular marker or laboratory tool capable of diagnosing autism at an early age. The purpose of this study is to explore the plausible use of peripheral biomarkers in the early diagnosis of autism via a sensitive ELISA. Here, we measured plasma secreted amyloid precursor protein alpha (sAPP-alpha) levels in autistic and aged-matched control blood samples and found a significantly increased level of sAPP-alpha in 60% of the known autistic children. We then tested 150 human umbilical cord blood (HUCB) samples and found significantly elevated levels of plasma sAPP-alpha in 10 of 150 samples. As an additional confirmatory measure, we performed Western blot analysis on these samples which consistently showed increased sAPP-alpha levels in autistic children and 10 of 150 HUCB samples; suggesting a group of autistic patients which could be identified in early childhood by levels of sAPP-alpha. While there is need for further studies of this concept, the measurement of sAPP-alpha levels in serum and human umbilical cord blood by ELISA is a potential tool for early diagnosis of autism.
2. Ekas NV, Whitman TL, Shivers C. {{Religiosity, Spirituality, and Socioemotional Functioning in Mothers of Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2008 (Dec 12)
Religious beliefs, religious activities, and spirituality are coping resources used by many mothers of children with autism spectrum disorder (ASD). This study examined whether and how these resources were related to maternal socioemotional functioning. Mothers of children with ASD completed questionnaires assessing religiosity, spirituality, and a wide range of outcome variables, including stress, depression, self-esteem, life satisfaction, positive affect, and sense of control. Analyses revealed that religious beliefs and spirituality were associated with better positive outcomes and, to a lesser extent, lower levels of negative outcomes. Of the two predictors, spirituality accounted for more unique variance in positive outcomes. In contrast, religious activities were related to more negative outcomes and lower levels of positive outcomes.
3. Fischer M, Reuter J, Gerich FJ, Hildbrandt B, Hagele S, Katschinski D, Mueller M. {{Enhanced Hypoxia Susceptibility in Hippocampal Slices from a Mouse Model of Rett Syndrome}}.{ J Neurophysiol};2008 (Dec 10)
Rett syndrome is a neurodevelopmental disorder caused by mutations in the X-chromosomal MECP2 gene encoding for the transcriptional regulator methyl CpG binding protein 2 (MeCP2). Rett patients suffer from episodic respiratory irregularities and reduced arterial oxygen levels. To elucidate whether such intermittent hypoxic episodes induce adaptation/preconditioning of the hypoxia-vulnerable hippocampal network, we analyzed its responses to severe hypoxia in adult Rett mice. The occurrence of hypoxia-induced spreading depression (HSD) – an experimental model for ischemic stroke – was hastened in Mecp2(-/y)males. The extracellular K(+) rise during HSD was attenuated in Mecp2(-/y) males and the input resistance of CA1 pyramidal neurons decreased less before HSD onset. CA1 pyramidal neurons were smaller and more densely packed, but the cell swelling during HSD was unaffected. The intrinsic optical signal and the propagation of HSD were similar among the different genotypes. Basal synaptic function was intact, but Mecp2(-/y) males showed reduced paired-pulse facilitation, higher field potential/fiber volley ratios but no increased seizure susceptibility. Synaptic failure during hypoxia was complete in all genotypes and the final degree of posthypoxic synaptic recovery indistinguishable. Cellular ATP content was normal in Mecp2(-/y) males, but their hematocrit was increased as was HIF-1alpha expression throughout the brain. This is the first study showing that in Rett syndrome, the susceptibility of telencephalic neuronal networks to hypoxia is increased; the underlying molecular mechanisms apparently involve disturbed K(+) channel function. Such an increase in hypoxia susceptibility may potentially contribute to the vulnerability of male Rett patients who are either not viable or severely disabled.
4. Garcia-Rudaz C, Deng V, Matagne V, Ronnekleiv O, Bosch M, Han V, Percy AK, Ojeda SR. {{FXYD1, a modulator of Na(+),K(+)-ATPase activity, facilitates female sexual development by maintaining GnRH neuronal excitability}}. {J Neuroendocrinol};2008 (Dec 6)
Abstract The excitatory tone to GnRH neurones is a critical component underlying the pubertal increase in GnRH secretion. However, the homeostatic mechanisms modulating the response of GnRH neurones to excitatory inputs remain poorly understood. A basic mechanism of neuronal homeostasis is the Na(+), K(+)-ATPase-dependent restoration of Na(+) and K(+) transmembrane gradients after neuronal excitation. This activity is reduced in a mouse model of Rett syndrome (RTT), a neurodevelopmental disorder in which expression of FXYD1, a modulator of Na(+), K(+)-ATPase activity, is increased. We now report that the initiation, but not the completion of puberty, is advanced in girls with RTT, and that in rodents FXYD1 may contribute to the neuroendocrine regulation of female puberty by modulating GnRH neuronal excitability. Fxyd1 mRNA abundance reaches maximal levels in the female rat hypothalamus by the fourth postnatal week of life, i.e., around the time when the mode of GnRH secretion acquires an adult pattern of release. Although Fxyd1 mRNA expression is low in the hypothalamus, about 50% of GnRH neurones contain Fxyd1 transcripts. Whole-cell patch recording of GnRH-EGFP neurones revealed that the neurones of Fxyd1-null female mice respond to somatic current injections with a lower number of action potentials than wild-type cells. Both the age at vaginal opening and at first oestrous were delayed in Fxyd1(-/-) mice, but adult reproductive capacity was normal. These results suggest that FXYD1 contributes to facilitating the advent of puberty by maintaining GnRH neuronal excitability to incoming transsynaptic stimulatory inputs.
5. Gilby KL. {{A new rat model for vulnerability to epilepsy and autism spectrum disorders}}. {Epilepsia};2008 (Nov);49 Suppl 8:108-110.
Tremendous concern has arisen in response to the recent diagnostic outbreak of childhood developmental disorders, particularly involving attention deficit hyperactivity disorder (ADHD) and the autism spectrum disorders (ASD). Interestingly, similarities in clinical presentation across these disorders may suggest common predisposing factors. For instance, though not widely recognized, an increased predisposition toward seizure is a symptom that is very often associated with ADHD and ASD. Accordingly, a rat strain naturally bred to be seizure-prone simultaneously developed behavioral and physical characteristics analogous to those observed in ADHD/ASD patients. These rats also show early signs of aberrant lipid handling, which is another symptom common to human patients with these disorders. As such, this rat strain could serve as an excellent model system through which to identify common pathophysiological events that constitute a »spectrum of vulnerability »toward ADHD/ASD and epilepsy.
6. Gotham K, Pickles A, Lord C. {{Standardizing ADOS Scores for a Measure of Severity in Autism Spectrum Disorders}}. {J Autism Dev Disord};2008 (Dec 12)
The aim of this study is to standardize Autism Diagnostic Observation Schedule (ADOS) scores within a large sample to approximate an autism severity metric. Using a dataset of 1,415 individuals aged 2-16 years with autism spectrum disorders (ASD) or nonspectrum diagnoses, a subset of 1,807 assessments from 1,118 individuals with ASD were divided into narrow age and language cells. Within each cell, severity scores were based on percentiles of raw totals corresponding to each ADOS diagnostic classification. Calibrated severity scores had more uniform distributions across developmental groups and were less influenced by participant demographics than raw totals. This metric should be useful in comparing assessments across modules and time, and identifying trajectories of autism severity for clinical, genetic, and neurobiological research.
7. Gras-Vincendon A, Bursztejn C, Danion JM. {{[Functioning of memory in subjects with autism.]}}. {Encephale};2008 (Dec);34(6):550-556.Fonctionnement de la memoire chez les sujets avec autisme.
INTRODUCTION: Autism is an early developmental disorder with cognitive impairments that leads to learning and social integration disabilities. The characterization of memory functions in individuals with autism has been the subject of numerous investigations, with widely varying conclusions. The notable differences between these studies can be attributed to variations in the age, intelligence and level of severity of the participants with autism. LITERATURE FINDINGS: The purpose of our review of the recent literature is to describe the memory function of individuals with autism. Some of the different memory subtypes are intact, others are impaired. Short-term memory (digit span) is not impaired while working memory is impaired in some of its components, but the findings are inconsistent. More recent studies demonstrate reduced spatial working memory abilities in autism and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory. Episodic long-term memory, as measured by free recall, cued recall or recognition tasks, is intact, but participants with autism perform significantly less well than controls as the complexity of the verbal or visual material to be recalled increases. Source or contextual memory involves a variety of characteristics specifying the conditions under which specific items or facts are acquired: it has been investigated in individuals with autism with different methods. Deficits in source memory for temporal information have been found, but there were no reality monitoring deficits. Recent findings indicate that the nature of source memory confusion in autism does not appear to reflect a generalized deficit in attaching context to memories, but rather is dependant on the specific to-be-remembered information that involves social aspects of context. The self-reference effect is missing, with individuals with autism recalling events performed by themselves less well than the events performed by a peer, suggesting they have difficulties in relation to processes involving the self. Studies involving assessment of subjective states of awareness during recognition show less conscious recollection and more feelings of familiarity. Recent investigations are consistent in demonstrating memory impairments related to the failure of subjects with autism to use organizing strategies or meaning to support memory, an effect which grows with the increasing complexity of the material. Memory deficits in autism may be related more to retrieval and less to encoding, as deficit in source memory in participants with autism is largely eliminated when source was supported at test. DISCUSSION: The neuroanatomical basis of the specificities of memory impairment in autism is still uncertain, but it is suggested that autism involves an impairment in the conversion of limbic inputs into medial prefrontal outputs. Memory deficits found in individuals with autism may explain some of the clinical symptoms. Failure to encode all the information, especially its social aspects, may therefore contribute to dysfunction in the social, communication, and reasoning domains. Abnormal memory functioning in autism is also related to more general cognitive impairments, including executive function deficits and central coherence weakness. Evidence of the normality of certain memory capacities, at least in individuals with moderate autistic symptomatology, is encouraging for adaptive improvements in cognitive functioning.
8. Hartman AL. {{Does the effectiveness of the ketogenic diet in different epilepsies yield insights into its mechanisms?}} {Epilepsia};2008 (Nov);49 Suppl 8:53-56.
The ketogenic diet (KD) has been used successfully in a variety of epilepsy syndromes. This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. It also includes syndromes where genetics play a major role, such as Dravet syndrome, tuberous sclerosis, and Rett syndrome. Study of the KD in humans and animals harboring various genetic mutations may yield insights into the diet’s mechanisms. Comparison of the diet’s effectiveness with other treatments in specific syndromes may be another useful tool for mechanistic studies. The diet’s utility in epilepsy syndromes of various etiologies and in some neurodegenerative disorders suggests it may have multiple mechanisms of action.
9. Hoeffer CA, Tang W, Wong H, Santillan A, Patterson RJ, Martinez LA, Tejada-Simon MV, Paylor R, Hamilton SL, Klann E. {{Removal of FKBP12 Enhances mTOR-Raptor Interactions, LTP, Memory, and Perseverative/Repetitive Behavior}}. {Neuron};2008 (Dec 10);60(5):832-845.
FK506-binding protein 12 (FKBP12) binds the immunosuppressant drugs FK506 and rapamycin and regulates several signaling pathways, including mammalian target of rapamycin (mTOR) signaling. We determined whether the brain-specific disruption of the FKBP12 gene in mice altered mTOR signaling, synaptic plasticity, and memory. Biochemically, the FKBP12-deficient mice displayed increases in basal mTOR phosphorylation, mTOR-Raptor interactions, and p70 S6 kinase (S6K) phosphorylation. Electrophysiological experiments revealed that FKBP12 deficiency was associated with an enhancement in long-lasting hippocampal long-term potentiation (LTP). The LTP enhancement was resistant to rapamycin, but not anisomycin, suggesting that altered translation control is involved in the enhanced synaptic plasticity. Behaviorally, FKBP12 conditional knockout (cKO) mice displayed enhanced contextual fear memory and autistic/obsessive-compulsive-like perseveration in several assays including the water maze, Y-maze reversal task, and the novel object recognition test. Our results indicate that FKBP12 plays a critical role in the regulation of mTOR-Raptor interactions, LTP, memory, and perseverative behaviors.
10. Houlihan LM, Harris SE, Luciano M, Gow AJ, Starr JM, Visscher PM, Deary IJ. {{Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936}}. {Genes Brain Behav};2008 (Dec 10)
As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified SNPs within candidate genes that might influence cognition or age-related cognitive change. This study investigated ten candidate genes in over 1,000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in ten genes previously associated with cognition, Alzheimer’s disease or autism were genotyped in 1,063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN. Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, co-varying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 (P < 0.05). No SNPs reached the Bonferroni-level of significance (all P-values > 0.0015). Of the ten genes, we discuss that COMT, KL, PRNP, PPP1R1B, SORL1 and WRN especially merit further attention for association with cognitive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition.
11. Mostafa GA, El-Sayed ZA, El-Aziz MM, El-Sayed MF. {{Serum anti-myelin-associated glycoprotein antibodies in Egyptian autistic children}}. {J Child Neurol};2008 (Dec);23(12):1413-1418.
Autoimmunity to brain could play an etiopathogenic role in a subgroup of autistic patients. The frequency of serum anti-myelin-associated glycoprotein antibodies, as an index for autoimmunity to brain, and their relation to family history of autoimmunity were investigated in 32 autistic and 32 healthy matched children. Autistic children had significantly higher serum anti-myelin-associated glycoprotein antibodies than healthy children (2100 [1995] and 1138 [87.5] Buhlmann titre unit, P < .001). Anti-myelin-associated glycoprotein positivity was elicited in 62.5% of autistic children. Family history of autoimmunity in autistic children (50%) was significantly higher than controls (9.4%). Anti-myelin-associated glycoprotein serum levels were significantly higher in autistic children with than those without such history (P < .05). In conclusion, autism could be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further studies are warranted to shed light on the etiopathogenic role of anti-myelin-associated glycoprotein antibodies and the role of immunotherapy in autism.
12. Muller RA. {{From loci to networks and back again: anomalies in the study of autism}}. {Ann N Y Acad Sci};2008 (Dec);1145:300-315.
Recent developments in functional imaging as well as the emergence of new anatomical imaging techniques suited for the study of white matter have shifted investigational paradigms from a localized to a more holistic network approach. Aside from detecting local activity, functional MRI can be applied to the study of connectivity. However, the concept of « functional connectivity » remains broad, and specific designs and analyses may affect the results. In addition, connectivity cannot be viewed in isolation. Rather, from a developmental perspective, connectivity and local cortical architecture are intimately related. Therefore, combined approaches examining local organization and connectivity are the most promising avenues for elucidating disturbances of neurofunctional organization in developmental disorders. Here this approach is illustrated via data obtained from autism research that suggest impaired local cortical architecture and reduced long-range connectivity between cerebral regions.
13. Niklasson L, Rasmussen P, Oskarsdottir S, Gillberg C. {{Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome}}. {Res Dev Disabil};2008 (Dec 12)
This study assessed the prevalence and type of associated neuropsychiatric problems in children and adults with 22q11 deletion syndrome. One-hundred consecutively referred individuals with 22q11 deletion syndrome were given in-depth neuropsychiatric assessments and questionnaires screens. Autism spectrum disorders (ASDs) and/or attention deficit/hyperactivity disorder (ADHD) were diagnosed in 44 cases. ASD was diagnosed in 23 cases of whom only 5 had autistic disorder. ADHD was diagnosed in 30 individuals. In nine of these cases with ASD or ADHD there was a combination of these diagnoses. Mental retardation (MR) with or without ASD/ADHD was diagnosed in 51 individuals. ASD, ADHD, and/or MR were present in 67 cases. Females had higher IQ than males. The results of this study showed that the vast majority of all individuals with 22q11 deletion syndrome have behavior and/or learning problems and more than 40% meet criteria for either ASD, ADHD or both. Neuropsychiatric and neuropsychological evaluations are indicated as parts of the routine clinical assessment of individuals with 22q11 deletion syndrome.
14. Pelphrey KA, Carter EJ. {{Brain mechanisms for social perception: lessons from autism and typical development}}. {Ann N Y Acad Sci};2008 (Dec);1145:283-299.
In this review, we summarize our research program, which has as its goal charting the typical and atypical development of the social brain in children, adolescents, and adults with and without autism. We highlight recent work using virtual reality stimuli, eye tracking, and functional magnetic resonance imaging that has implicated the superior temporal sulcus (STS) region as an important component of the network of brain regions that support various aspects of social cognition and social perception. Our work in typically developing adults has led to the conclusion that the STS region is involved in social perception via its role in the visual analysis of others’ actions and intentions from biological-motion cues. Our work in high-functioning adolescents and adults with autism has implicated the STS region as a mechanism underlying social perception dysfunction in this neurodevelopmental disorder. We also report novel findings from a study of biological-motion perception in young children with and without autism.
15. Roberts JE, Mankowski JB, Sideris J, Goldman BD, Hatton DD, Mirrett PL, Baranek GT, Reznick JS, Bailey DB, Jr. {{Trajectories and Predictors of the Development of Very Young Boys with Fragile X Syndrome}}. {J Pediatr Psychol};2008 (Dec 12)
OBJECTIVE: To describe the development of young boys with fragile X syndrome (FXS). METHODS: Fifty-five boys (aged 8-48 months at study entry) with the full mutation FXS received multiple developmental assessments. RESULTS: As expected, the boys’ rate of development was significantly lower than chronological age expectations. No evidence of slowing in the rate of development was found. Autistic behavior was negatively associated with development, but maternal IQ was not. Developmental delays were evident in some domains as early as 9 months; however, initial detection of delays is complicated by measures and criteria used. Developmental age scores at 31 months of age were related to scores obtained at 61 months of age only in the global composite and visual reception domain. CONCLUSIONS: Developmental delays are evident in some infants with FXS as young as 9 months of age. Pediatric psychologists need to be informed about the developmental profiles in young children with FXS to accurately diagnose, treat, and support these children and their families.
16. Romero-Rubio MT, Andres-Celma M, Castello-Pomares ML, Rosello M, Ferrer-Bolufer I, Martinez-Castellano F. {{[ARX mutations and mental retardation of unknown etiology: three new cases in Spain.]}}. {Rev Neurol};2008 (Dec 16-31);47(12):634-637.Mutaciones en el gen ARX y retraso mental no filiado: tres nuevos casos en Espana.
INTRODUCTION. Mental retardation has an approximated prevalence of 2% in the general population and its most frequent cause is X-fragile syndrome. This genetic disorder predominantly affects males and it is mainly caused by the expansion of CGG in FMR1 gene. Recently has been demonstrated that mutations in a new called ARX gene (aristaless-related homeobox) can also cause a similar form of X linked mental retardation, as well as other neurological disorders (autism, Partington or West syndrome). The most frequent mutation that has been reported is the c.428_451 dup24, which comprises almost 60% of all described. It causes an expansion of a polyalanine tract of ARX protein. CASE REPORTS. We report three cases of mental retardation in two different families where the mutation in ARX gene c.428_451 dup24 was found while X-fragile syndrome screening was made. Personal and familiar history, phenotype and evolution are described. CONCLUSION. The molecular analysis of this mutation should be considered as a routine for the genetic diagnosis of mental retardation in males of nondrafted cause.
17. Spek A, Schatorje T, Scholte E, van Berckelaer-Onnes I. {Verbal fluency in adults with high functioning autism or Asperger syndrome}. {Neuropsychologia};2008 (Nov 24)
The semantic and phonemic fluency performance of adults with high functioning autism (HFA), Asperger syndrome and a neurotypical control group were compared. All participants were matched for age and verbal ability. Results showed that the participants with HFA were significantly impaired in their performance of both semantic fluency tasks and the phonemic fluency task using the letter M. The Asperger group was only impaired in their performance of the semantic fluency tasks ‘professions’. The social components of the ‘professions’ task may have influenced the performance of the two disorder groups for this subtest negatively. The fluency deficits could not be attributed to a lack of the use of strategies or to difficulties in switching between strategies. The impairment in two of the three verbal fluency subtests in the HFA group can be attributed to the relatively low processing speed found in this group.
18. Spreng RN, McKinnon MC, Mar RA, Levine B. {{The toronto empathy questionnaire: scale development and initial validation of a factor-analytic solution to multiple empathy measures}}. {J Pers Assess};2009 (Jan);91(1):62-71.
To formulate a parsimonious tool to assess empathy, we used factor analysis on a combination of self-report measures to examine consensus and developed a brief self-report measure of this common factor. The Toronto Empathy Questionnaire (TEQ) represents empathy as a primarily emotional process. In 3 studies, the TEQ demonstrated strong convergent validity, correlating positively with behavioral measures of social decoding, self-report measures of empathy, and negatively with a measure of Autism symptomatology. Moreover, it exhibited good internal consistency and high test-retest reliability. The TEQ is a brief, reliable, and valid instrument for the assessment of empathy.
19. Stein MT, Drahota A, Chavira DA. {{Ian: a 7-year old with prenatal drug exposure and early exposure to family violence}}. {J Dev Behav Pediatr};2008 (Dec);29(6):512-515.
CASE: A 7(1/2)-year-old boy is brought to a new primary care pediatrician because his grandparents, who have legal custody, want a « fresh look » at his behavior. Ian’s grandmother begins the history with the comment, « He started out kind of rough. » He was exposed to methamphetamine and marijuana throughout gestation and his mother had bipolar disease and hypertension. A Cesarean section for failure to progress was followed by normal Apgar scores and an unremarkable neonatal course. Ian’s parents physically fought during the first 6 months of his life; at that time, the parents separated and the grandparents assumed care. Ian was expelled from three preschools due to physical aggression directed at other children. He also found it difficult to separate from his grandmother. In first grade, Ian often ran out of the classroom and was verbally, and at one time, physically abuse to his teacher. When he was expelled from school, the grandparents decided to home school Ian. Ian learned to read about 100 words and his spelling improved. Currently, Ian is in the first grade in a class of 10 children with behavioral problems; Ian has his own aid to insure his safety while in school. His teacher reports frequent fidgety behavior, difficulty sitting in his seat or at circle time, and trouble focusing on learning tasks. While his grandparents describe Ian as a « sweet and happy » child at home, they are concerned with repetitive behaviors (e.g., frequent flushing of the toilet because he worried that it is broken and brushing his teeth over 10 times each day), fear of leaving the house, and insisting on order to certain things such as his toys and having a « meltdown » when they are not in order. Severe tantrums are limited to once each month. A receptive and expressive language disorder was diagnosed at 4-years old followed by speech therapy and a social skills-language group program. A few months before the current pediatric visit, Ian had psychoeducational testing: The Wechsler Intelligence Scale-IV revealed verbal intelligence quotient (IQ) of 75 and a performance IQ of 108 with a full scale score of 81. The Gilliam Autism Rating Scale-2 indicated a probability of autism with significant scores in stereotype behavior, communication, and social interactions. During the physical examination, he constantly moved while in chair and required frequent redirection and refocusing on many tasks. Eye contact was appropriate, but he often used words out of context with scripted references to videos at home. Foul language was used both randomly and directed to the examiner. After saying, « here comes the bitch, » he apologized. Ian demonstrated appropriate joint attention and reciprocal play without over-focusing on a single toy. Growth measurements were at the 95th percentile. Physical and neurological examinations were normal with the exception of mild asymmetry of auricle size and slightly abducted auricles in association with mildly small palpebral fissures.
20. Vincent JB, Noor A, Windpassinger C, Gianakopoulos PJ, Schwarzbraun T, Alfred SE, Stachowiak B, Scherer SW, Roberts W, Wagner K, Kroisel PM, Petek E. {{Characterization of a de novo translocation t(5;18)(q33.1;q12.1) in an autistic boy identifies a breakpoint close to SH3TC2, ADRB2, and HTR4 on 5q, and within the desmocollin gene cluster on 18q}}. {Am J Med Genet B Neuropsychiatr Genet};2008 (Dec 11)
We have recently reported the identification of a de novo balanced translocation t(5;18)(q33.1;q12.1) in a boy with autism. Here we discuss the identification of the breakpoints on chromosomes 5 and 18, and subsequent genomic and candidate gene analyses. The 18q breakpoint lies between desmocollin genes DSC1 and DSC2. The chromosome 5 breakpoint lies at the 3′ end of the SH3TC2 gene and distal to beta-adrenergic receptor gene ADRB2 and serotonin receptor gene HTR4. We hypothesized that the transcription of one (or more) of these genes is affected by the translocation by position effect. Looking at allele-specific gene expression for the genes at the 5q locus, we were able to determine that ADRB2 is expressed from both the normal and derivative alleles. Due to the lack of expression in available tissues or lack of available informative transcribed SNPs, we were unable to exclude the involvement of SH3TC2 and HTR4 due to position effect. However, we determined that both DSC1 and DSC2 are only transcribed from the normal chromosome 18 in lymphocytes from the proband. This monoallelic expression of DSC2 may put the patient at risk for arrythmogenic right ventricular cardiomyopathy. Desmocollin genes encode cell-adhesion molecules, and are also highly expressed in brain regions, and thus may also be important for normal neuronal functioning. While a role for SH3TC2, ADRB2, and HTR4 as putative candidate genes for autism cannot be discounted, a role for the desmocollin genes at the 18q breakpoint should also be considered. (c) 2008 Wiley-Liss, Inc.
21. Zeegers M, Pol HH, Durston S, Nederveen H, Schnack H, Daalen EV, Dietz C, Engeland HV, Buitelaar J. {{No differences in MR-based volumetry between 2- and 7-year-old children with autism spectrum disorder and developmental delay}}. {Brain Dev};2008 (Dec 8)
OBJECTIVE: To study brain volumes in children with ASD as compared to children with a mental retardation or a language delay (developmentally delayed). In addition, to study the association of intellectual functioning on brain volumes in children with ASD or developmental delay. Methods: Thirty-four children with ASD and 13 developmentally delayed children without ASD, between 2 and 7 years old, matched on age and developmental level, participated in a MRI study. Volumes of cranium, total brain, cerebellum, grey and white matter, ventricles, hippocampus and amygdala were measured. Results: No significant differences in volumes of intracranium, total brain, ventricles, cerebellum, grey or white matter or amygdala and hippocampus between the ASD group and the developmentally delayed group were found. In the developmentally delayed group, a significant correlation (0.73) was found between intellectual functioning and total brain volume after partialling out intracranial volume. In the ASD group, the correlation between intellectual functioning and brain volume corrected for intracranial volume was not significant. Conclusion: No evidence was found for overall differences in brain volumes in children with ASD compared to developmentally delayed children between 2 and 7 years. The finding that higher intellectual functioning was not associated with a relative larger brain volume in children with ASD may suggest that a relative enlargement of the brain may not be beneficial to patients with autism.
22. {{[Psychotic spectrum disorders in childhood]}}. {Srp Arh Celok Lek};2008 (Sep-Oct);136(9-10):555-558.
For a long time, there was a strong belief of existing continuity between childhood-onset psychoses and adult psychoses. Important moment in understanding psychotic presentations during infancy and childhood is Kanner’s description of early infantile autism. Later studies of Rutter and Kolvin, as well as new classification systems, have delineated pervasive developmental disorders from all other psychotic disorders in childhood. But clinical experience is showing that in spite of existence of the group of pervasive developmental disorders with subgroups within it and necessary diagnostic criteria–there are children with pervasive symptoms, who are not fulfilling all necessary diagnostic criteria for pervasive developmental disorder. Therefore, in this paper we are discussing and pointing at psychotic spectrum presentations in children, which have not the right place in any existing classification system (ICD-10, DSM-IV).
