1. Al-Qabandi M, Gorter JW, Rosenbaum P. {{Early Autism Detection: Are We Ready for Routine Screening?}}. {Pediatrics};2011 (Jun 13)
BACKGROUND: Autism is a serious neurodevelopmental disorder that has a reportedly rising prevalence rate. The American Academy of Pediatrics recommends that screening for autism be incorporated into routine practice. It is important to consider the pros and cons of conducting autism screening as part of routine practice and its implications on the community. We have explored this question in the context of screening from a scientific point of view. Method: A literature search was conducted to assess the effectiveness of community screening programs for autism. Results: Judged against critical questions about autism, screening programs failed to fulfill most criteria. Good screening tools and efficacious treatment are lacking, and there is no evidence yet that such a program would do more good than harm. Conclusions: On the basis of the available research, we believe that we do not have enough sound evidence to support the implementation of a routine population-based screening program for autism. Ongoing research in this field is certainly needed, including the development of excellent screening instruments and demonstrating with clinical trials that such programs work and do more good than harm.
2. Baker JK, Seltzer MM, Greenberg JS. {{Longitudinal effects of adaptability on behavior problems and maternal depression in families of adolescents with autism}}. {J Fam Psychol};2011 (Jun 13)
Research on families of individuals with autism has tended to focus on child-driven effects utilizing models of stress and coping. The current study used a family systems perspective to examine whether family level adaptability promoted beneficial outcomes for mothers and their adolescents with autism over time. Participants were 149 families of children diagnosed with autism who were between the ages of 10 and 22 years during the 3-year period examined. Mothers reported on family adaptability, the mother-child relationship, their own depressive symptoms, and the behavior problems of their children at Wave 1, and these factors were used to predict maternal depression and child behavior problems 3 years later. Family level adaptability predicted change in both maternal depression and child behavior problems over the study period, above and beyond the contribution of the dyadic mother-child relationship. These associations did not appear to depend upon the intellectual disability status of the individual with autism. Implications for autism, parent mental health, family systems theory, and intervention with this population are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
3. Baret L, Godard B. {{Opinions and intentions of parents of an autistic child toward genetic research results: two typical profiles}}. {Eur J Hum Genet};2011 (Jun 15)
Returning results to research participants is increasingly acknowledged in research ethics guidelines. But few research teams actually do it or provide mechanisms for offering it as an option. We explored the perspective of parents of an autistic child participating in genetic research. In all, 388 questionnaires were sent to 194 parents; 158 questionnaires were completed (89 mothers and 69 fathers), giving a response rate of 41%. 97% of respondents (n=153) fully expressed a strong desire to receive research results, either general or individual ones. The survey solicited parents’ opinions as to what means could be put in place to return research results. The majority held the research team responsible for returning individual results (79.7%, n=126). They indicated that it should occur at the completion of the research project (69%, n=109), by mail (75.3%, n=119). Over three quarters felt the Ministry of Health should cover the associated costs (77.8%, n=123). If the communication of individual findings, whether positive or negative, were to be possible, these would allow some respondents ‘to be prepared for the future’ (37%, n=57), without necessarily having practical benefits (21%, n=32), but at least bringing them ‘relief or understanding’ (14%, n=21). Moreover, parents were clear about the difference between research and clinical settings. This study underlines the importance of broadening the discussion about the communication of research results, especially individual ones. We believe that the integration of different perspectives – those of researchers, clinicians, ethics committees and participants – will enrich the debate and offer enlightenment for future ethical guidelines.European Journal of Human Genetics advance online publication, 15 June 2011; doi:10.1038/ejhg.2011.106.
4. Blankenship K, Erickson CA, Stigler KA, Posey DJ, McDougle CJ. {{Guanfacine extended release in two patients with pervasive developmental disorders}}. {J Child Adolesc Psychopharmacol};2011 (Jun);21(3):287-290.
5. Breau LM, Camfield CS. {{Pain disrupts sleep in children and youth with intellectual and developmental disabilities}}. {Res Dev Disabil};2011 (Jun 9)
Both chronic pain and sleep problems are common for children with intellectual and developmental disabilities (IDD). Although one study has revealed a relationship between having a medical condition and sleep problems in this population, the role of pain was not examined independently. Thus, the goal of this study was to clarify the specific role of pain in children’s sleep problems. Caregivers of 123 children with IDD (67 male; mean age=10 years, 7 months (SD=49.7 months)) completed the Children’s Sleep Habits Questionnaire (CHSQ) and provided information about children’s pain, function and demographic characteristics. Children were grouped as having: No Pain (86), Treated Pain (21), or Untreated Pain (16). A Multivariate Analysis of Variance (MANOVA) indicated children who had pain had significantly more sleep problems overall (F(16, 222)=2.2, p=.005), and more Night Wakings (F(2, 118)=3.1, p=.05), Parasomnias (F(2, 118)=5.0, p=.009) and Sleep Disordered Breathing (F(2, 118)=5.1, p=.008) in particular. The pattern of sleep problems varied due to whether the child was taking pain medication. Children with pain also had significantly shorter typical sleep duration (F(2, 112)=3.5, p=0.035). The presence of sleep problems did not vary due to functional level or whether children were taking sleep medications. However, parents of children who were taking sleep medications reported that both Bedtime Resistance (F(1, 121)=5.7, p=.019) and Sleep Duration (F(1, 121)=6.0, p=.016) were more problematic for them. This data indicates pain disrupts sleep in children with IDD even when it is being managed pharmacologically, suggesting pain treatment may not be effective. These results suggest that pain should be considered during evaluation and management of sleep problems in children with IDD.
6. Chiri G, Warfield ME. {{Unmet Need and Problems Accessing Core Health Care Services for Children with Autism Spectrum Disorder}}. {Matern Child Health J};2011 (Jun 11)
To investigate the health care experiences of children with autism spectrum disorder, whether they have unmet needs, and if so, what types, and problems they encounter accessing needed care. We address these issues by identifying four core health care services and access problems related to provider and system characteristics. Using data from the 2005-2006 National Survey of Children with Special Health Care Needs (NS-CSHCN) we compared children with autism spectrum disorder with children with special health care needs with other emotional, developmental or behavioral problems (excluding autism spectrum disorder) and with other children with special health care needs. We used weighted logistic regression to examine differences in parent reports of unmet needs for the three different health condition groups. Overall unmet need for each service type among CSHCN ranged from 2.5% for routine preventive care to 15% for mental health services. After controlling for predisposing, enabling and need factors, some differences across health condition groups remained. Families of children with autism spectrum disorder were in fact significantly more at risk for having unmet specialty and therapy care needs. Additionally, families of children with autism spectrum disorder were more likely to report provider lack of skills to treat the child as a barrier in obtaining therapy and mental health services. Disparities in unmet needs for children with autism suggest that organizational features of managed care programs and provider characteristics pose barriers to accessing care.
7. Clopper CG, Rohrbeck KL, Wagner L. {{Perception of Dialect Variation by Young Adults with High-Functioning Autism}}. {J Autism Dev Disord};2011 (Jun 14)
The linguistic profile of people with Autism spectrum disorders typically involves intact perceptual processing, accompanied by deficits in the social functions of language. In a series of three experiments, the impact of this profile on the perception of regional dialect was examined. Young adults with High-Functioning Autism exhibited similar performance to a typically developing comparison group in regional dialect classification and localness rating tasks, suggesting that they can use indexical information in speech to make judgments about the regional background of unfamiliar talkers. However, the participants with High-Functioning Autism were less able to differentiate among the dialects in a language attitudes task, suggesting that they do not share social stereotypes related to dialect variation with the typically developing comparison group.
8. Courchesne E, Karns C, Davis H, Ziccardi R, Carper R, Tigue Z, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln A, Pizzo S, Schreibman L, Haas R, Akshoomoff N, Courchesne R. {{Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study}}. {Neurology};2011 (Jun 14);76(24):2111.
9. Fassio A, Patry L, Congia S, Onofri F, Piton A, Gauthier J, Pozzi D, Messa M, Defranchi E, Fadda M, Corradi A, Baldelli P, Lapointe L, St-Onge J, Meloche C, Mottron L, Valtorta F, Khoa Nguyen D, Rouleau GA, Benfenati F, Cossette P. {{SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function}}. {Hum Mol Genet};2011 (Jun 15);20(12):2297-2307.
Several genes predisposing to autism spectrum disorders (ASDs) with or without epilepsy have been identified, many of which are implicated in synaptic function. Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis. This nonsense mutation was found in all affected individuals from a large French-Canadian family segregating epilepsy and ASDs. Additional mutations in SYN1 (A51G, A550T and T567A) were found in 1.0 and 3.5% of French-Canadian individuals with autism and epilepsy, respectively. The majority of these SYN1 mutations were clustered in the proline-rich D-domain which is substrate of multiple protein kinases. When expressed in synapsin I (SynI) knockout (KO) neurons, all the D-domain mutants failed in rescuing the impairment in the size and trafficking of synaptic vesicle pools, whereas the wild-type human SynI fully reverted the KO phenotype. Moreover, the nonsense Q555X mutation had a dramatic impact on phosphorylation by MAPK/Erk and neurite outgrowth, whereas the missense A550T and T567A mutants displayed impaired targeting to nerve terminals. These results demonstrate that SYN1 is a novel predisposing gene to ASDs, in addition to epilepsy, and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.
10. Howell PC, Larson J, Coffey DB. {{Treatment of bipolar disorder in an adolescent with autistic disorder: a diagnostic and treatment dilemma}}. {J Child Adolesc Psychopharmacol};2011 (Jun);21(3):283-286.
11. Kopp S, Gillberg C. {{The Autism Spectrum Screening Questionnaire (ASSQ)-Revised Extended Version (ASSQ-REV): An instrument for better capturing the autism phenotype in girls? A preliminary study involving 191 clinical cases and community controls}}. {Res Dev Disabil};2011 (Jun 8)
We wanted to develop and validate an extension of the Autism Spectrum Screening Questionnaire (ASSQ)-the ASSQ Revised Extended Version (ASSQ-REV) – for better capturing the female phenotype of autism spectrum disorders (ASD). Clinic girls and Clinic boys, most of whom with ASD and/or attention-deficit/hyperactivity disorder (ADHD), and Community girls without a clinical diagnosis of any kind of neuropsychiatric disorder were compared on the results of the parent-rated ASSQ and on a new set of items (ASSQ-GIRL). The ASSQ-REV discriminated well between cases and non-cases. Certain single ASSQ-GIRL items were much more typical of girls than of boys with ASD. The most striking of these were « avoids demands », « very determined », « careless with physical appearance and dress » and « interacts mostly with younger children ». The issue of whether or not there is a gender-specific ASD for phenotype is discussed.
12. Marcus RN, Owen R, Manos G, Mankoski R, Kamen L, McQuade RD, Carson WH, Corey-Lisle PK, Aman MG. {{Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study}}. {J Child Adolesc Psychopharmacol};2011 (Jun);21(3):229-236.
Abstract Aim: To report the long-term efficacy of aripiprazole in the treatment of irritability in children and adolescents (ages 6-17 years) with autistic disorder. Methods: This was a 52-week, open-label, flexible-dose (2-15 mg/day) study of aripiprazole for the treatment of children and adolescents with irritability associated with autistic disorder. Eligible subjects were enrolled from two 8-week randomized trials or were enrolled as de novo subjects. « Prior aripiprazole » subjects had received treatment with aripiprazole for 8 weeks before entering this study. Evaluation of efficacy, a secondary objective after evaluation of safety and tolerability in this study, was conducted using the caregiver-rated Aberrant Behavior Checklist-Irritability subscale and the clinician-rated Clinical Global Impression-Improvement score. Results: Three hundred thirty subjects received treatment (de novo, n = 86; prior aripiprazole, n = 174; prior placebo, n = 70) and 199 subjects (60.3%) completed 52 weeks of treatment. At their last study visit, 38.2% of subjects were receiving concomitant central nervous system medications (commonly antidepressants, 13.4%; psychostimulants, 11.5%; antiepileptics, 5.9%). At week 52 (observed cases data set), the mean change from baseline in Aberrant Behavior Checklist Irritability subscale scores was -8.0 in de novo subjects and -6.1 in prior placebo subjects; prior aripiprazole subjects maintained symptom improvement that was achieved with treatment in the prior study. At endpoint, the majority of subjects had a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved). Conclusion: Aripiprazole reduced symptoms of irritability associated with autistic disorder in pediatric subjects ages 6-17 years who were studied for up to 1 year.
13. Mironov S, Skorova E, Hartelt N, Mironova LA, Hasan MT, Kugler S. {{Erratum to: Remodelling of the respiratory network in a mouse model of Rett syndrome depends on brain-derived neurotrophic factor regulated slow calcium buffering by S. L. Mironov, E. Skorova, N. Hartelt, L. A. Mironova, M. T. Hasan, and S. Kugler. J Physiol June 1, 2009 587 (11) 2473-2485; doi:10.1113/jphysiol.2009.169805}}. {J Physiol};2011 (Jun 13)
The article by Mironov et al. (2009) contained an error in Fig. 7B. Figure 7 should have appeared as follows. It should be noted that the error does not alter results or discussion in the text.
14. Roberts JE, Miranda M, Boccia M, Janes H, Tonnsen BL, Hatton DD. {{Treatment effects of stimulant medication in young boys with fragile X syndrome}}. {J Neurodev Disord};2011 (Jun 14)
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by a CGG repeat expansion at Xq27.3 on the FMR1 gene. The majority of young boys with FXS display poor attention and hyperactivity that is disproportionate to their cognitive disability, and approximately 70% meet diagnostic criteria for attention-deficit/hyperactivity disorder. Psychopharmacology is employed with 82% of young males 5-17 years of age, with stimulant medication as the most common medication prescribed. This study evaluated the effects of stimulant medication on the academic performance, attention, motor activity, and psychophysiological arousal of boys with FXS, as well as the concordance of effects within individuals. Participants in this study included 12 boys with FXS who were treated with stimulants. Participants completed videotaped academic testing on two consecutive days and were randomly assigned to be off stimulants for 1 day and on stimulants the other day. On each day, multiple measures including academic performance, behavior regulation, and psychophysiological arousal were collected. Approximately 75% of participants performed better on attention and academic measures, and 70% showed improved physiological regulation while on stimulant medication. A high degree of concordance among measures was found. Lower intelligence quotient (IQ), but not age, correlated with greater improvements in in-seat behavior. IQ and age did not relate to on-task behaviors. The frequency and magnitude of response to stimulant medication in boys with FXS is higher than those reported for most children with non-specific intellectual disabilities and autism spectrum disorder.
15. Scahill L, McCracken JT, Bearss K, Robinson F, Hollander E, King B, Bregman J, Sikich L, Dukes K, Sullivan L, Anagnostou E, Donnelly C, Kim YS, Ritz L, Hirtz D, Wagner A. {{Design and Subject Characteristics in the Federally-Funded Citalopram Trial in Children with Pervasive Developmental Disorders}}. {J Autism Dev Disord};2011 (Jun 11)
The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (+/-3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger’s Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.
16. Sherk Y, Smith BA, Miller BD. {{Liquid Melatonin via Gastrostomy as an Alternative Hypnotic in a Child with Pervasive Developmental Disorder}}. {J Child Adolesc Psychopharmacol};2011 (Jun);21(3):291-293.
17. Siller SS, Broadie K. {{Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase}}. {Dis Model Mech};2011 (Jun 13)
Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1) null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ), clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP) in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single dfmr1 mutants and controls. These results support minocycline as a promising potential FXS treatment and suggest that it might act via MMP inhibition. We conclude that FMRP and TIMP pathways interact in a reciprocal, bidirectional manner.
