Papers of the Week
J Child Neurol. 2013 Nov 25. [Epub ahead of print]
Case Report: Neuronal Migration Disorder Associated With Chromosome 15q13.3 Duplication in a Boy With Autism and Seizures.
1Saul R. Korey Department of Neurology and Epilepsy Management Center, Albert
Einstein college of Medicine and Montefiore Medical Center, Bronx, NY, USA.
Neuronal migration disorders are a group of disorders that cause structural brain
abnormalities and varying degrees of neurocognitive impairment, resulting from
abnormal neuronal migration during brain development. There are several mutations
that have been associated with these disorders. Here the case of a 4-year-old
autistic boy is presented, who was found to have evidence of a neuronal migration
disorder on magnetic resonance imaging (MRI) during a workup for seizures.
Genetic testing did not reveal any of the gene mutations known to be associated
with neuronal migration disorders but did reveal a microduplication at chromosome
15q13.3, a locus that has been previously associated with autism, cognitive
impairment, and seizures. Although the concurrent presence of the genetic and
structural abnormalities does not necessarily imply causality, the simultaneous
independent occurrence of both conditions is certainly unusual. It is possible
that there may be an association between this duplication syndrome and aberrant
PMID: 24282185 [PubMed - as supplied by publisher]
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Neuroimage Clin. 2013 Sep 19;3:321-331.
Mentalizing and motivation neural function during social interactions in autism spectrum disorders.
Assaf M, Hyatt CJ, Wong CG, Johnson MR, Schultz RT, Hendler T, Pearlson GD.
Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT, USA ;
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Autism Spectrum Disorders (ASDs) are characterized by core deficits in social
functions. Two theories have been suggested to explain these deficits:
mind-blindness theory posits impaired mentalizing processes (i.e. decreased
ability for establishing a representation of others' state of mind), while social
motivation theory proposes that diminished reward value for social information
leads to reduced social attention, social interactions, and social learning.
Mentalizing and motivation are integral to typical social interactions, and
neuroimaging evidence points to independent brain networks that support these
processes in healthy individuals. However, the simultaneous function of these
networks has not been explored in individuals with ASDs. We used a social,
interactive fMRI task, the Domino game, to explore mentalizing- and
motivation-related brain activation during a well-defined interval where
participants respond to rewards or punishments (i.e. motivation) and concurrently
process information about their opponent's potential next actions (i.e.
mentalizing). Thirteen individuals with high-functioning ASDs, ages 12-24, and 14
healthy controls played fMRI Domino games against a computer-opponent and
separately, what they were led to believe was a human-opponent. Results showed
that while individuals with ASDs understood the game rules and played similarly
to controls, they showed diminished neural activity during the human-opponent
runs only (i.e. in a social context) in bilateral middle temporal gyrus (MTG)
during mentalizing and right Nucleus Accumbens (NAcc) during reward-related
motivation (Pcluster < 0.05 FWE). Importantly, deficits were not observed in
these areas when playing against a computer-opponent or in areas related to motor
and visual processes. These results demonstrate that while MTG and NAcc, which
are critical structures in the mentalizing and motivation networks, respectively,
activate normally in a non-social context, they fail to respond in an otherwise
identical social context in ASD compared to controls. We discuss implications to
both the mind-blindness and social motivation theories of ASD and the importance
of social context in research and treatment protocols.
PMID: 24273716 [PubMed - as supplied by publisher]
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J Psychiatr Res. 2013 Nov 9. pii: S0022-3956(13)00339-7. doi:
10.1016/j.jpsychires.2013.10.022. [Epub ahead of print]
Genome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder.
Ramos-Quiroga JA, Sánchez-Mora C, Casas M, Garcia-Martínez I, Bosch R, Nogueira
M, Corrales M, Palomar G, Vidal R, Coll-Tané M, Bayés M, Cormand B, Ribasés M.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain;
Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain;
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona,
Attention-deficit and hyperactivity disorder (ADHD) is a common psychiatric
disorder with a worldwide prevalence of 5-6% in children and 4.4% in adults.
Recently, copy number variations (CNVs) have been implicated in different
neurodevelopmental disorders such as ADHD. Based on these previous reports that
focused on pediatric cohorts, we hypothesize that structural variants may also
contribute to adult ADHD and that such genomic variation may be enriched for CNVs
previously identified in children with ADHD. To address this issue, we performed
for the first time a whole-genome CNV study on 400 adults with ADHD and 526
screened controls. In agreement with recent reports in children with ADHD or in
other psychiatric disorders, we identified a significant excess of insertions in
ADHD patients compared to controls. The overall rate of CNVs >100 kb was 1.33
times higher in ADHD subjects than in controls (p = 2.4e-03), an observation
mainly driven by a higher proportion of small events (from 100 kb to 500 kb;
1.35-fold; p = 1.3e-03). These differences remained significant when we
considered CNVs that overlap genes or when structural variants spanning candidate
genes for psychiatric disorders were evaluated, with duplications showing the
greatest difference (1.41-fold, p = 0.024 and 2.85-fold, p = 8.5e-03,
respectively). However, no significant enrichment was detected in our ADHD cohort
for childhood ADHD-associated CNVs, CNVs previously identified in at least one
ADHD patient or CNVs previously implicated in autism or schizophrenia. In
conclusion, our study provides tentative evidence for a higher rate of CNVs in
adults with ADHD compared to controls and contributes to the growing list of
structural variants potentially involved in the etiology of the disease.
Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID: 24269040 [PubMed - as supplied by publisher]
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Dev Psychopathol. 2013 Nov 27:1-14. [Epub ahead of print]
Development of autobiographical memory in children with autism spectrum disorders: Deficits, gains, and predictors of performance.
Goddard L, Dritschel B, Robinson S, Howlin P.
University of London, London.
Autobiographical memory (AM) was assessed in 63 children (aged 8-17 years) with
an autism spectrum disorder (ASD) and compared with 63 typically developing
children matched for age, gender, IQ, and verbal ability. A range of
methodologies was employed for eliciting past experience with particular focus on
the ability to recall (a) specific events, (b) the recent and remote past, and
(c) semantic versus episodic memories across different lifetime periods. Results
indicated that the ASD group manifested difficulties in retrieving specific
memories to word cues and had poorer access to the remote past. Deficits were
found in the context of intact recent memory and preserved general memory
abilities, with some impairment of visual memory. Problems in retrieving episodic
and semantic AMs across the life span were also evident. Qualitative analysis of
memory reports suggested that the ASD group was less likely to refer to emotion
in their remote memories but more likely to describe emotions in their recent
memories. Important predictors of AM performance in the ASD group were central
executive abilities, in particular cognitive flexibility and verbal fluency.
PMID: 24284059 [PubMed - as supplied by publisher]
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J Autism Dev Disord. 2013 Nov 27. [Epub ahead of print]
Joint Attention Initiation With and Without Positive Affect: Risk Group Differences and Associations with ASD Symptoms.
Gangi DN, Ibañez LV, Messinger DS.
Department of Psychology, University of Miami, 5665 Ponce de Leon Blvd, Coral
Gables, FL, 33146, USA, firstname.lastname@example.org.
Infants at risk for autism spectrum disorders (ASD) may have difficulty
integrating smiles into initiating joint attention (IJA) bids. A specific IJA
pattern, anticipatory smiling, may communicate preexisting positive affect when
an infant smiles at an object and then turns the smile toward the social partner.
We compared the development of anticipatory smiling at 8, 10, and 12 months in
infant siblings of children with ASD (high-risk siblings) and without ASD
(low-risk siblings). High-risk siblings produced less anticipatory smiling than
low-risk siblings, suggesting early differences in communicating preexisting
positive affect. While early anticipatory smiling distinguished the risk groups,
IJA not accompanied by smiling best predicted later severity of ASD-related
behavioral characteristics among high-risk siblings. High-risk infants appear to
show lower levels of motivation to share positive affect with others. However,
facility with initiating joint attention in the absence of a clear index of
positive affective motivation appears to be central to the prediction of ASD
PMID: 24281421 [PubMed - as supplied by publisher]
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Brain Stimul. 2013 Oct 27. pii: S1935-861X(13)00299-4. doi:
10.1016/j.brs.2013.10.004. [Epub ahead of print]
A Double-blind, Randomized Trial of Deep Repetitive Transcranial Magnetic Stimulation (rTMS) for Autism Spectrum Disorder.
Enticott PG, Fitzgibbon BM, Kennedy HA, Arnold SL, Elliot D, Peachey A, Zangen A,
Monash Alfred Psychiatry Research Centre, The Alfred and Central Clinical School,
Monash University, Level 4, 607 St Kilda Road, Melbourne, Victoria 3004,
Australia. Electronic address: email@example.com.
BACKGROUND: Biomedical treatment options for autism spectrum disorder (ASD) are
extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe
and efficacious technique when targeting specific areas of cortical dysfunction
in major depressive disorder, and a similar approach could yield therapeutic
benefits in ASD, if applied to relevant cortical regions.
OBJECTIVE: The aim of this study was to examine whether deep rTMS to bilateral
dorsomedial prefrontal cortex improves social relating in ASD.
METHODS: 28 adults diagnosed with either autistic disorder (high-functioning) or
Asperger's disorder completed a prospective, double-blind, randomized,
placebo-controlled design with 2 weeks of daily weekday treatment. This involved
deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration,
20-s inter-train interval) for 15 min (1500 pulses per session) using a
HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep
rTMS coil, but no effective field was delivered into the brain. Assessments were
conducted before, after, and one month following treatment.
RESULTS: Participants in the active condition showed a near significant reduction
in self-reported social relating symptoms from pre-treatment to one month
follow-up, and a significant reduction in social relating symptoms (relative to
sham participants) for both post-treatment assessments. Those in the active
condition also showed a reduction in self-oriented anxiety during difficult and
emotional social situations from pre-treatment to one month follow-up. There were
no changes for those in the sham condition.
CONCLUSION: Deep rTMS to bilateral dorsomedial prefrontal cortex yielded a
reduction in social relating impairment and socially-related anxiety. Further
research in this area should employ extended rTMS protocols that approximate
those used in depression in an attempt to replicate and amplify the clinical
Copyright © 2013 Elsevier Inc. All rights reserved.
PMID: 24280031 [PubMed - as supplied by publisher]
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J Exerc Rehabil. 2013 Apr;9(2):220-229. Epub 2013 Apr 25.
Treadmill exercise improves behavioral outcomes and spatial learning memory through up-regulation of reelin signaling pathway in autistic rats.
Seo TB, Cho HS, Shin MS, Kim CJ, Ji ES, Baek SS.
Department of Biochemistry, Division of Sports Science & Engineering, Korea
Institute of Sports Science, Seoul, Korea.
Autism is a complex neurodevelopmental disability with impairments of social
interaction and communication, and repetitive behavior. Reelin is an
extracellular glycoprotein that is essential for neuronal migration and brain
development. Neuroprotective effects of exercise on various brain insults are
well documented, however, the effects of exercise on autism in relation with
reelin expression are not clarified. In the present study, we investigated the
effects of treadmill exercise on the functional recovery and on the expressions
of reelin and its downstream molecules, phosphatidylinositol-3-kinase (PI3K),
phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated protein
kinase 1 and 2 (p-ERK1/2), using autistic rats. For the induction of autism-like
animal model, 400 mg/kg valproic acid was subcutaneously injected into the rats
on the postnatal day 14. The rat in the treadmill exercise groups were forced to
run on a treadmill for 30 min once a day, five times a week for 4 weeks, starting
postnatal day 28. To investigate autism-like behaviors and memory deficit, open
field, social interaction, and radial 8-arm maze were performed.
Immunohistochemistry and western blotting were conducted. In the present results,
treadmill exercise alleviated aggressive tendency and improved correct decision
in the spatial learning memory in the autistic rats. Treadmill exercise increased
neurogenesis and the expressions of reelin and its down-stream molecules, PI3K,
p-Akt, and p-ERK1/2, in the hippocampus of the autistic rats. The present study
showed that treadmill exercise ameliorated aggressive behavior and improved
spatial learning memory through activation of reeling signaling pathway in the
valproic acid-induced autistic rats.
PMID: 24278864 [PubMed - as supplied by publisher]
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PLoS One. 2013 Nov 20;8(11):e80126. doi: 10.1371/journal.pone.0080126.
The Brain's Response to the Human Voice Depends on the Incidence of Autistic Traits in the General Population.
Yoshimura Y, Kikuchi M, Ueno S, Okumura E, Hiraishi H, Hasegawa C, Remijn GB,
Shitamichi K, Munesue T, Tsubokawa T, Higashida H, Minabe Y.
Research Center for Child Mental Development, Kanazawa University, Kanazawa,
Optimal brain sensitivity to the fundamental frequency (F0) contour changes in
the human voice is important for understanding a speaker's intonation, and
consequently, the speaker's attitude. However, whether sensitivity in the brain's
response to a human voice F0 contour change varies with an interaction between an
individual's traits (i.e., autistic traits) and a human voice element (i.e.,
presence or absence of communicative action such as calling) has not been
investigated. In the present study, we investigated the neural processes involved
in the perception of F0 contour changes in the Japanese monosyllables "ne" and
"nu." "Ne" is an interjection that means "hi" or "hey" in English; pronunciation
of "ne" with a high falling F0 contour is used when the speaker wants to attract
a listener's attention (i.e., social intonation). Meanwhile, the Japanese
concrete noun "nu" has no communicative meaning. We applied an adaptive spatial
filtering method to the neuromagnetic time course recorded by whole-head
magnetoencephalography (MEG) and estimated the spatiotemporal frequency dynamics
of event-related cerebral oscillatory changes in beta band during the oddball
paradigm. During the perception of the F0 contour change when "ne" was presented,
there was event-related de-synchronization (ERD) in the right temporal lobe. In
contrast, during the perception of the F0 contour change when "nu" was presented,
ERD occurred in the left temporal lobe and in the bilateral occipital lobes. ERD
that occurred during the social stimulus "ne" in the right hemisphere was
significantly correlated with a greater number of autistic traits measured
according to the Autism Spectrum Quotient (AQ), suggesting that the differences
in human voice processing are associated with higher autistic traits, even in
PMID: 24278247 [PubMed - in process]
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Brain. 2013 Nov 25. [Epub ahead of print]
Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders.
Grabrucker S, Jannetti L, Eckert M, Gaub S, Chhabra R, Pfaender S, Mangus K,
Reddy PP, Rankovic V, Schmeisser MJ, Kreutz MR, Ehret G, Boeckers TM, Grabrucker
1 WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocentre of
Ulm University, Ulm, Germany.
Proteins of the ProSAP/Shank family act as major organizing scaffolding elements
within the postsynaptic density of excitatory synapses. Deletions, mutations or
the downregulation of these molecules has been linked to autism spectrum
disorders, the related Phelan McDermid Syndrome or Alzheimer's disease.
ProSAP/Shank proteins are targeted to synapses depending on binding to zinc,
which is a prerequisite for the assembly of the ProSAP/Shank scaffold. To gain
insight into whether the previously reported assembly of ProSAP/Shank through
zinc ions provides a crossing point between genetic forms of autism spectrum
disorder and zinc deficiency as an environmental risk factor for autism spectrum
disorder, we examined the interplay between zinc and ProSAP/Shank in vitro and in
vivo using neurobiological approaches. Our data show that low postsynaptic zinc
availability affects the activity dependent increase in ProSAP1/Shank2 and
ProSAP2/Shank3 levels at the synapse in vitro and that a loss of synaptic
ProSAP1/Shank2 and ProSAP2/Shank3 occurs in a mouse model for acute and prenatal
zinc deficiency. Zinc-deficient animals displayed abnormalities in behaviour such
as over-responsivity and hyperactivity-like behaviour (acute zinc deficiency) and
autism spectrum disorder-related behaviour such as impairments in vocalization
and social behaviour (prenatal zinc deficiency). Most importantly, a low zinc
status seems to be associated with an increased incidence rate of seizures,
hypotonia, and attention and hyperactivity issues in patients with
Phelan-McDermid syndrome, which is caused by haploinsufficiency of
ProSAP2/Shank3. We suggest that the molecular underpinning of prenatal zinc
deficiency as a risk factor for autism spectrum disorder may unfold through the
deregulation of zinc-binding ProSAP/Shank family members.
PMID: 24277719 [PubMed - as supplied by publisher]
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Autism. 2013 Nov 25. [Epub ahead of print]
Understanding the gap between cognitive abilities and daily living skills in adolescents with autism spectrum disorders with average intelligence.
Duncan AW, Bishop SL.
1Cincinnati Children's Hospital Medical Center, USA.
Daily living skills standard scores on the Vineland Adaptive Behavior Scales-2nd
edition were examined in 417 adolescents from the Simons Simplex Collection. All
participants had at least average intelligence and a diagnosis of autism spectrum
disorder. Descriptive statistics and binary logistic regressions were used to
examine the prevalence and predictors of a "daily living skills deficit," defined
as below average daily living skills in the context of average intelligence
quotient. Approximately half of the adolescents were identified as having a daily
living skills deficit. Autism symptomatology, intelligence quotient, maternal
education, age, and sex accounted for only 10% of the variance in predicting a
daily living skills deficit. Identifying factors associated with better or worse
daily living skills may help shed light on the variability in adult outcome in
individuals with autism spectrum disorder with average intelligence.
PMID: 24275020 [PubMed - as supplied by publisher]
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Dev Psychopathol. 2013 Nov 25:1-12. [Epub ahead of print]
Patterns of skill attainment and loss in young children with autism.
Thurm A, Manwaring SS, Luckenbaugh DA, Lord C, Swedo SE.
National Institute of Mental Health.
The purpose of this study was to extend the literature on the ontogeny of autism
spectrum disorder (ASD) by examining early attainment and loss of specific
sociocommunicative skills in children with autism (AUT; n = 125), pervasive
developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum
developmental delays (n = 46), and typical development (n = 31). The ages of
skill attainment and loss were obtained from a caregiver interview. The findings
indicated that children with AUT, PDD-NOS, and developmental delays diverged from
typically developing children in attainment of sociocommunicative skills early in
the first year of life. Loss of at least one skill was reported in a majority of
children with AUT and PDD-NOS. Significant delays in attainment of skills were
also reported in children who lost skills. The wide variation in skill attainment
and loss reported across children indicates that symptom onset and regression may
be best represented continuously, with at least some early delay and loss present
for a great majority of children with ASD.
PMID: 24274034 [PubMed - as supplied by publisher]
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J Autism Dev Disord. 2013 Nov 28. [Epub ahead of print]
Engagement in Vocational Activities Promotes Behavioral Development for Adults with Autism Spectrum Disorders.
Taylor JL, Smith LE, Mailick MR.
Vanderbilt Kennedy Center, Peabody Box 40, 230 Appleton Place, Nashville, TN,
37203, USA, Julie.firstname.lastname@example.org.
This study examined the bidirectional relations over time between behavioral
functioning (autism symptoms, maladaptive behaviors, activities of daily living)
and vocational/educational activities of adults with autism spectrum disorders
(ASD). Participants were 153 adults with ASD (M age = 30.2 years) who were part
of a larger longitudinal study. Data were collected at two time points separated
by 5.5 years. Cross-lag models were used, which accounted for stability over time
while testing both directions of cross-lagged effects. Results suggested that
greater vocational independence and engagement was related to subsequent
reductions in autism symptoms and maladaptive behaviors, and improvements in
activities of daily living. Relations between earlier behavioral variables
(symptoms, behaviors, and activities of daily living) and later vocational
independence were not statistically significant.
PMID: 24287880 [PubMed - as supplied by publisher]
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Genes Brain Behav. 2013 Nov 28. doi: 10.1111/gbb.12109. [Epub ahead of print]
Microbial Genes, Brain & Behaviour - Epigenetic Regulation of the Gut-Brain Axis.
Stilling RM, Dinan TG, Cryan JF.
Alimentary Pharmabiotic Center, University College Cork, Ireland.
To date, there is rapidly increasing evidence for host-microbe interaction on
virtually all levels of complexity, ranging from direct cell-to-cell
communication to extensive systemic signalling, and involving various organs and
organ systems, including the central nervous system. As such, the discovery that
differential microbial composition is associated with alterations in behaviour
and cognition has significantly contributed to establish the microbiota-gut-brain
axis as an extension of the well-accepted gut-brain axis concept. Many efforts
have been focused on delineating a role for this axis in health and disease
ranging from stress-related disorders such as depression, anxiety and irritable
bowel syndrome to neurodevelopmental disorders such as autism. There is also a
growing appreciation of the role of epigenetic mechanisms in shaping brain and
behaviour. However, the role of epigenetics in informing host-microbe
interactions has received little attention to date. This is despite the fact that
there are many plausible routes of interaction between epigenetic mechanisms and
the host-microbiota dialogue. From this new perspective we put forward novel, yet
testable, hypotheses. Firstly, we suggest that gut-microbial products can affect
chromatin plasticity within their host's brain that in turn leads to changes in
neuronal transcription and eventually alters host behaviour. Secondly, we argue
that the microbiota is an important mediator of gene-environment interactions.
Finally, we reason that the microbiota itself may be viewed as an epigenetic
entity. In conclusion, the fields of (neuro)epigenetics and microbiology are
converging at many levels and more interdisciplinary studies are necessary to
unravel the full range of this interaction.
This article is protected by copyright. All rights reserved.
PMID: 24286462 [PubMed - as supplied by publisher]
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Front Syst Neurosci. 2013 Nov 14;7:83.
New roles for the cerebellum in health and disease.
Reeber SL, Otis TS, Sillitoe RV.
Department of Pathology and Immunology, Department of Neuroscience, Baylor
College of Medicine, Jan and Dan Duncan Neurological Research Institute of Texas
Children's Hospital Houston, TX, USA.
The cerebellum has a well-established role in maintaining motor coordination and
studies of cerebellar learning suggest that it does this by recognizing neural
patterns, which it uses to predict optimal movements. Serious damage to the
cerebellum impairs this learning and results in a set of motor disturbances
called ataxia. However, recent work implicates the cerebellum in cognition and
emotion, and it has been argued that cerebellar dysfunction contributes to
non-motor conditions such as autism spectrum disorders (ASD). Based on human and
animal model studies, two major questions arise. Does the cerebellum contribute
to non-motor as well as motor diseases, and if so, how does altering its function
contribute to such diverse symptoms? The architecture and connectivity of
cerebellar circuits may hold the answers to these questions. An emerging view is
that cerebellar defects can trigger motor and non-motor neurological conditions
by globally influencing brain function. Furthermore, during development
cerebellar circuits may play a role in wiring events necessary for higher
cognitive functions such as social behavior and language. We discuss genetic,
electrophysiological, and behavioral evidence that implicates Purkinje cell
dysfunction as a major culprit in several diseases and offer a hypothesis as to
how canonical cerebellar functions might be at fault in non-motor as well as
PMID: 24294192 [PubMed - as supplied by publisher]
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Cereb Cortex. 2013 Nov 28. [Epub ahead of print]
Cognitive Abilities on Transitive Inference Using a Novel Touchscreen Technology for Mice.
Silverman JL, Gastrell PT, Karras MN, Solomon M, Crawley JN.
MIND Institute, Department of Psychiatry and Behavioral Science, University of
California Davis School of Medicine, Sacramento, CA 95817, USA.
Cognitive abilities are impaired in neurodevelopmental disorders, including
autism spectrum disorder (ASD) and schizophrenia. Preclinical models with strong
endophenotypes relevant to cognitive dysfunctions offer a valuable resource for
therapeutic development. However, improved assays to test higher order cognition
are needed. We employed touchscreen technology to design a complex transitive
inference (TI) assay that requires cognitive flexibility and relational learning.
C57BL/6J (B6) mice with good cognitive skills and BTBR T+tf/J (BTBR), a model of
ASD with cognitive deficits, were evaluated in simple and complex touchscreen
assays. Both B6 and BTBR acquired visual discrimination and reversal. BTBR
displayed deficits on components of TI, when 4 stimuli pairs were interspersed,
which required flexible integrated knowledge. BTBR displayed impairment on the A
> E inference, analogous to the A > E deficit in ASD. B6 and BTBR mice both
reached criterion on the B > D comparison, unlike the B > D impairment in
schizophrenia. These results demonstrate that mice are capable of complex
discriminations and higher order tasks using methods and equipment paralleling
those used in humans. Our discovery that a mouse model of ASD displays a TI
deficit similar to humans with ASD supports the use of the touchscreen technology
for complex cognitive tasks in mouse models of neurodevelopmental disorders.
PMID: 24293564 [PubMed - as supplied by publisher]
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J Autism Dev Disord. 2013 Nov 29. [Epub ahead of print]
Rigid-Compulsive Behaviors are Associated with Mixed Bowel Symptoms in Autism Spectrum Disorder.
Peters B, Williams KC, Gorrindo P, Rosenberg D, Lee EB, Levitt P,
Vanderbilt University, 1601 23rd Avenue South, Suite 300, Nashville, TN, 37212,
Based on clinical experience, we hypothesized that rigid-compulsive behaviors are
associated with severe constipation and co-occurring diarrhea or underwear
staining in children with autism spectrum disorder. Using data from the Autism
Treatment Network, we evaluated the association between these gastrointestinal
symptoms and measures of rigid compulsive behavior in children ages 2-17.
Following statistical correction, four of five primary measures were
significantly associated with constipation and diarrhea or underwear staining,
including parental report of repetitive behavior, parental report of compulsive
behavior, clinician diagnosis of obsessive-compulsive disorder, and report of
rituals observed on the autism diagnostic observation schedule. This association
could point to a causal connection between these symptoms or to a common
biological pathway that impacts both gut and brain.
PMID: 24293040 [PubMed - as supplied by publisher]
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Int J Pediatr Otorhinolaryngol. 2013 Nov 14. pii: S0165-5876(13)00557-0. doi:
10.1016/j.ijporl.2013.10.065. [Epub ahead of print]
Autism spectrum disorders in 24 children who are deaf or hard of hearing.
Meinzen-Derr J, Wiley S, Bishop S, Manning-Courtney P, Choo DI, Murray D.
Divisions of Biostatistics and Epidemiology, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, USA; Pediatric Otolaryngology, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address:
OBJECTIVES: Approximately 4% of children who are deaf or hard of hearing have
co-occurring autism spectrum disorder (ASD). Making an additional diagnosis of
ASD in this population can be challenging, given the complexities of determining
whether speech/language and social delays can be accounted for by their hearing
loss, or whether these delays might be indicative of a comorbid ASD diagnosis.
This exploratory study described a population of 24 children with the dual
diagnosis of ASD and hearing loss.
METHODS: Children completed a comprehensive ASD evaluation using standardized
autism diagnostic instruments (Autism Diagnostic Observation Schedule, language
and psychological testing). Children with permanent hearing loss who had a
developmental evaluation between 2001 and 2011 and were diagnosed with an ASD
based on the results of that evaluation were included. Information on
communication modality, language and cognitive abilities was collected.
RESULTS: The median age of diagnosis was 14 months (range 1-71) for hearing loss
and 66.5 months (range 33-106) for ASD. Only 25% (n=6) children were diagnosed
with ASD ≤48 months of age and 46% by ≤6 years. Twelve (50%) children were
diagnosed with ASD, 11 were diagnosed with pervasive developmental disorder not
otherwise specified and 1 child had Asperger's. Most (67%) had profound degree of
hearing loss. Fourteen (58%) children had received a cochlear implant, while 3
children had no amplification for hearing loss. Nine (38%) of the 24 children
used speech as their mode of communication (oral communicators).
CONCLUSIONS: Communication delays in children who are deaf or hard of hearing are
a serious matter and should not be assumed to be a direct consequence of the
hearing loss. Children who received cochlear implants completed a
multidisciplinary evaluation including a developmental pediatrician, which may
have provided closer monitoring of speech and language progression and
subsequently an earlier ASD diagnosis. Because children who are deaf or hard of
hearing with ASD are challenging to evaluate, they may receive a diagnosis of ASD
at older ages.
Copyright © 2013. Published by Elsevier Ireland Ltd.
PMID: 24290951 [PubMed - as supplied by publisher]
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Compr Psychiatry. 2013 Oct 10. pii: S0010-440X(13)00240-X. doi:
10.1016/j.comppsych.2013.08.001. [Epub ahead of print]
Quality of life: A case-controlled long-term follow-up study, comparing young high-functioning adults with autism spectrum disorders with adults with other psychiatric disorders diagnosed in childhood.
Barneveld PS, Swaab H, Fagel S, van Engeland H, de Sonneville LM.
Department of Clinical Child and Adolescent Studies, Leiden University, Leiden,
The Netherlands. Electronic address: email@example.com.
BACKGROUND: Long term outcome in childhood autism spectrum disorders (ASD) was
evaluated by studying quality of life (QoL) in young adulthood in comparison to
the outcome of other child psychiatric disorders.
METHODS: In this follow-up study, objective and subjective QoL of 169
high-functioning (IQ>70) adults with ASD (19 to 30years) was contrasted with QoL
data of age matched adults diagnosed with attention deficit/hyperactivity
disorder (N=85), disruptive behaviour disorders (N=83), and affective disorders
(N=85) during childhood. The mean follow-up period of the ASD patients was
13.9years. Objective QoL included marital status, living arrangements, level of
education, employment, and usage of mental health care. Subjective QoL included
satisfaction concerning living arrangements, work or education, physical
condition, partner relationship, social relationships, state of mind, and future
RESULTS: QoL was more compromised in adults diagnosed with ASD in childhood than
in adults with other psychiatric disorders in childhood. A relatively large
proportion of the adults with ASD were single, few lived with a partner or a
family and many of them were institutionalized. Adults with ASD had lower
educational levels, relatively few had paid employment and many were social
security recipients, as compared to the other psychiatric patients. In case the
adults with ASD used medication, 47% used anti-psychotics. Regarding the
subjective QoL, the adults with ASD were less satisfied about their work or
education, partner relationship, and future perspective than the other groups.
Even when highly educated adults with ASD were compared to highly educated adults
diagnosed with other childhood disorders, the QoL appeared to be more
disadvantageous in adults with ASD.
CONCLUSION: Many studies have shown that QoL is threatened in psychiatric
patients, but findings of this study indicate that young high-functioning adults
diagnosed with ASD in childhood are at relatively high risk for poor QoL compared
to other childhood psychiatric disorders.
PMID: 24290884 [PubMed - as supplied by publisher]
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Int Rev Neurobiol. 2013;113:35-59. doi: 10.1016/B978-0-12-418700-9.00002-2.
Contribution of Long Noncoding RNAs to Autism Spectrum Disorder Risk.
Wilkinson B, Campbell DB.
Program in Biological and Biomedical Sciences, University of Southern California,
Los Angeles, California, USA; Zilkha Neurogenetic Institute, University of
Southern California, Los Angeles, California, USA.
Accumulating evidence indicates that long noncoding RNAs (lncRNAs) contribute to
autism spectrum disorder (ASD) risk. Although a few lncRNAs have long been
recognized to have important functions, the vast majority of this class of
molecules remains uncharacterized. Because lncRNAs are more abundant in human
brain than protein-coding RNAs, it is likely that they contribute to brain
disorders, including ASD. We review here the known functions of lncRNAs and the
potential contributions of lncRNAs to ASD.
© 2013 Elsevier Inc. All rights reserved.
PMID: 24290382 [PubMed - in process]
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Int Rev Neurobiol. 2013;113:1-34. doi: 10.1016/B978-0-12-418700-9.00001-0.
Autism spectrum disorder and the cerebellum.
Becker EB, Stoodley CJ.
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics,
University of Oxford, Oxford, United Kingdom. Electronic address:
The cerebellum has been long known for its importance in motor learning and
coordination. Recently, anatomical, clinical, and neuroimaging studies strongly
suggest that the cerebellum supports cognitive functions, including language and
executive functions, as well as affective regulation. Furthermore, the cerebellum
has emerged as one of the key brain regions affected in autism. Here, we discuss
our current understanding of the role of the cerebellum in autism, including
evidence from genetic, molecular, clinical, behavioral, and neuroimaging studies.
Cerebellar findings in autism suggest developmental differences at multiple
levels of neural structure and function, indicating that the cerebellum is an
important player in the complex neural underpinnings of autism spectrum disorder,
with behavioral implications beyond the motor domain.
© 2013 Elsevier Inc. All rights reserved.
PMID: 24290381 [PubMed - in process]
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Dtsch Arztebl Int. 2013 Nov 8;110(45):755-63. doi: 10.3238/arztebl.2013.0755.
The investigation and differential diagnosis of asperger syndrome in adults.
Lehnhardt FG, Gawronski A, Pfeiffer K, Kockler H, Schilbach L, Vogeley K.
Department of Psychiatry and Psychotherapy, University of Cologne, Institute of
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3),
BACKGROUND: As a result of the increased public interest in autism spectrum
disorders (ASD), certain core manifestations of ASD-impaired social interaction
and communication, bizarre interests-are now commonly recognized as being typical
of autism, not only in children, but in adults as well. More often than before,
general practitioners, neurologists, and psychiatrists find themselves being
asked whether a patient is suffering from previously unrecognized Asperger
syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of
diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic
evaluation of AS in adulthood.
METHOD: We selectively searched the Medline database for pertinent literature,
paying special attention to diagnostic manuals and to the guideline of the United
Kingdom's National Institute for Health and Care Excellence (NICE).
RESULTS: Centrally important aspects of the diagnosis of AS include an assessment
of the patient's ability to assume the emotional perspectives of others,
non-verbal modes of expression, repetitive behavior patterns, and childhood
social behavioral history. The autism quotient (AQ) is now established as a
simple but nonspecific screening test. Up to 70% of all affected adults have
comorbid disturbances, most often depression and anxiety disorders. The
differential diagnosis includes personality disorders, anxiety disorders,
obsessive-compulsive disorder, and attention deficit-hyperactivity disorder. The
diagnostic assessment should proceed in stepwise fashion, starting from simple
screening in primary care and then moving on to evaluation of the suspected
diagnosis by a mental health care specialist, followed by extensive further
investigation in an outpatient clinic specifically devoted to patients with
autism spectrum disorders.
CONCLUSION: The diagnostic assessment of autism in adults requires knowledge of
the core and accompanying manifestations of autism and of their differential
diagnoses. More research is needed for the development of further screening tests
and the precise determination of diagnosis rates, differential diagnoses, nd
PMID: 24290364 [PubMed - in process]
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Mol Autism. 2013 Dec 1;4(1):47. [Epub ahead of print]
Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk?
Amiet C, Gourfinkel-An I, Laurent C, Bodeau N, Génin B, Leguern E, Tordjman S,
BACKGROUND: Autism spectrum disorders (ASD) and epilepsy frequently occur
together. Prevalence rates are variable, and have been attributed to age, gender,
comorbidity, subtype of pervasive developmental disorder (PDD) and risk factors.
Recent studies have suggested disparate clinical and genetic settings depending
on simplex or multiplex autism. The aim of this study was to assess: 1) the
prevalence of epilepsy in multiplex autism and its association with genetic and
non-genetic risk factors of major effect, intellectual disability and gender; and
2) whether autism and epilepsy cosegregate within multiplex autism families.
METHODS: We extracted from the Autism Genetic Resource Exchange (AGRE) database
(n = 3,818 children from 1,264 families) all families with relevant medical data
(n = 664 children from 290 families). The sample included 478 children with ASD
and 186 siblings without ASD. We analyzed the following variables: seizures,
genetic and non-genetic risk factors, gender, and cognitive functioning as
assessed by Raven's Colored Progressive Matrices (RCPM) and Vineland Adaptive
Behavior Scales (VABS).
RESULTS: The prevalence of epilepsy was 12.8% in cases with ASD and 2.2% in
siblings without ASD (P <10-5). With each RCPM or VABS measure, the risk of
epilepsy in multiplex autism was significantly associated with intellectual
disability, but not with gender. Identified risk factors (genetic or non-genetic)
of autism tended to be significantly associated with epilepsy (P = 0.052). When
children with prematurity, pre- or perinatal insult, or cerebral palsy were
excluded, a genetic risk factor was reported for 6/59 (10.2%) of children with
epilepsy and 12/395 (3.0%) of children without epilepsy (P = 0.002). Finally,
using a permutation test, there was significant evidence that the epilepsy
phenotype co-segregated within families (P <10-4).
CONCLUSIONS: Epilepsy in multiplex autism may define a different subgroup in
terms of clinical characteristics and genetic risk.
PMID: 24289166 [PubMed - as supplied by publisher]
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