Helping families find the best evidence: CAM therapies for autism spectrum disorders and Asperger's Disorder.

J Spec Pediatr Nurs. 2009 Jul;14(3):200-2

Authors: Abbey D

Family-Centered Care provides a forum for sharing information about basic components of caring for children and families, including respect, information sharing, collaboration, family-to-family support, and confidence building.

PMID: 19614829 [PubMed - indexed for MEDLINE]

What research questions matter to Australian paediatricians? National Delphi Study.

J Paediatr Child Health. 2009 Oct 26;

Authors: Rudolph S, Hiscock H, Price A, Efron D, Sewell J, South M, Wake M

Aim: The newly formed Australian Paediatric Research Network (APRN) aims to facilitate general paediatricians' participation in research in secondary care settings. This (its first) project aimed to identify Australian paediatricians' top research priorities and preferred research designs. Methods: All Australian general paediatricians were invited into a national Delphi process survey. In Stage 1, they were asked 'Thinking about your clinical practice, what are the most important research questions which need addressing?'. Using qualitative methods, a 'top 20' list of the most common, feasible research questions was generated. In Stage 2, respondents prioritised these 'top 20' research questions in terms of perceived importance to their practice, and rated their interest in participating in various types of research. Results: A total of 685 (68%) of 1006 paediatricians completed the baseline survey, with 209 paediatricians contributing 430 Stage 1 research questions. Of these, 128 (30%) had not been addressed in the literature and were researchable in the secondary care outpatient setting. The top five questions ranked in Stage 2 by 348 paediatricians were obesity management (two questions), long-term ADHD educational outcomes, autism spectrum outcomes, and prophylactic antibiotics in preventing urinary tract infections. Paediatricians were willing to participate in research designs, including longitudinal research (75%) and randomised trials (64%). Conclusions: Australian paediatricians are interested in research, and their ideas can provide direction for APRN and potentially other networks in Australia. Many of the questions generated could not be easily answered by traditional biomedical and clinical research methods, highlighting the potential benefit of practice-based research networks.

PMID: 19863713 [PubMed - as supplied by publisher]

Medication and Parent Training in Children With Pervasive Developmental Disorders and Serious Behavior Problems: Results From a Randomized Clinical Trial.

J Am Acad Child Adolesc Psychiatry. 2009 Oct 23;

Authors: Aman MG, McDougle CJ, Scahill L, Handen B, Arnold LE, Johnson C, Stigler KA, Bearss K, Butter E, Swiezy NB, Sukhodolsky DD, Ramadan Y, Pozdol SL, Nikolov R, Lecavalier L, Kohn AE, Koenig K, Hollway JA, Korzekwa P, Gavaletz A, Mulick JA, Hall KL, Dziura J, Ritz L, Trollinger S, Yu S, Vitiello B, Wagner A,

OBJECTIVE:: Many children with pervasive developmental disorders (PDDs) have serious, functionally impairing behavioral problems. We tested whether combined treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to medication alone (MED) in improving severe behavioral problems in children with PDDs. METHOD:: This 24-week, three-site, randomized, parallel-groups clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs, accompanied by frequent tantrums, self-injury, and aggression. The children were randomized 3:2 to COMB (n = 75) or MED (n = 49). The participants received risperidone monotherapy from 0.5 to 3.5 mg/day (with switch to aripiprazole if risperidone was ineffective). Parents in the COMB group (n = 75; 60.5%) received a mean of 10.9 PT sessions. The primary measure of compliance was the Home Situations Questionnaire (HSQ) score. RESULTS:: Primary: intent-to-treat random effects regression showed that COMB was superior to MED on HSQ (p =.006) [effect size at week 24 (d) = 0.34]. The HSQ score declined from 4.31 (+/-1.67) to 1.23 (+/-1.36) for COMB compared with 4.16 (+/-1.47) to 1.68 (+/-1.36) for MED. Secondary: groups did not differ on Clinical Global Impressions-Improvement scores at endpoint; compared with MED, COMB showed significant reductions on Aberrant Behavior Checklist Irritability (d = 0.48; p =.01), Stereotypic Behavior (d = 0.23; p =.04), and Hyperactivity/Noncompliance subscales (d = 0.55; p =.04). Final risperidone mean dose for MED was 2.26 mg/day (0.071 mg/kg), compared with 1.98 mg/day for COMB (0.066 mg/kg) (p =.04). CONCLUSIONS:: Medication plus PT resulted in greater reduction of serious maladaptive behavior than MED in children with PDDs, with a lower risperidone dose.Clinical trial registration information-RUPP PI PDD: Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders. URL: http://clinicaltrials.gov. Unique identifier: NCT00080145.

PMID: 19858761 [PubMed - as supplied by publisher]

Comorbidity study of ADHD: Applying association rule mining (ARM) to National Health Insurance Database of Taiwan.

Int J Med Inform. 2009 Oct 21;

Authors: Tai YM, Chiu HW

OBJECTIVE: This paper intends to apply association rule mining (ARM) to explore the labyrinthian network of ADHD comorbidity, and to examine the practicality of ARM in comorbidity studies using clinic databases. METHODS: From clinic records of enrollees of Taiwan National Health Insurance (NHI), 18,321 youngsters aged 18 or less with diagnosis of ADHD in 2001 were recruited as case group in this study. And all their clinic diagnoses made from 2000 to 2002, as comorbidity, were categorized according to "The International Classification of Disease, 9th Revision, Clinical Modification" (ICD-9-CM) diagnosis system. For comparison, fourfold non-ADHD controls were recruited from 2001s NHI enrollees on a random base but matched gender and age of cases. ARM was done with Apriori algorithm to examine the strengths of associations among those diagnoses. The support and confidence values of ARM results were examined. Comorbidity rates and relative risk (RR) ratios of both groups of each diagnosis were compared one another. RESULTS: ADHD case group has apparently higher risk of comorbidity with psychiatric comorbidity than with other physical illnesses. From results of ARM, developmental delay (DD) appears as an important node between ADHD and anxiety disorder (support: 5.12%, confidence: 97.42%), mild mental retardation (support: 4.42%, confidence: 92.09%) and autism (support: 6.49%, confidence: 94.93%). CONCLUSIONS: The finding of this study, an important role of DD between ADHD and other psychiatric comorbidity, supports neurological findings in developmental delay of ADHD children's front cortex, as well as some epidemiology findings. This study also demonstrated the practicality of ARM in comorbidity studies using enormous clinic databases like NHIRD.

PMID: 19853501 [PubMed - as supplied by publisher]

A common neural system mediating two different forms of social judgement.

Psychol Med. 2009 Oct 8;:1-10

Authors: Hall J, Whalley HC, McKirdy JW, Sprengelmeyer R, Santos IM, Donaldson DI, McGonigle DJ, Young AW, McIntosh AM, Johnstone EC, Lawrie SM

BACKGROUND: A wide range of neuropsychiatric conditions, including schizophrenia and autistic spectrum disorder (ASD), are associated with impairments in social function. Previous studies have shown that individuals with schizophrenia and ASD have deficits in making a wide range of social judgements from faces, including decisions related to threat (such as judgements of approachability) and decisions not related to physical threat (such as judgements of intelligence). We have investigated healthy control participants to see whether there is a common neural system activated during such social decisions, on the basis that deficits in this system may contribute to the impairments seen in these disorders.MethodWe investigated the neural basis of social decision making during judgements of approachability and intelligence from faces in 24 healthy participants using functional magnetic resonance imaging (fMRI). We used conjunction analysis to identify common brain regions activated during both tasks. RESULTS: Activation of the amygdala, medial prefrontal cortex, inferior prefrontal cortex and cerebellum was seen during performance of both social tasks, compared to simple gender judgements from the same stimuli. Task-specific activations were present in the dorsolateral prefrontal cortex in the intelligence task and in the inferior and middle temporal cortex in the approachability task. CONCLUSIONS: The present study identified a common network of brain regions activated during the performance of two different forms of social judgement from faces. Dysfunction of this network is likely to contribute to the broad-ranging deficits in social function seen in psychiatric disorders such as schizophrenia and ASD.

PMID: 19811702 [PubMed - as supplied by publisher]

The Role of the Theory-of-Mind Cortical Network in the Comprehension of Narratives.

Lang Linguist Compass. 2009 Jan 1;3(1):157-174

Authors: Mason RA, Just MA

Narrative comprehension rests on the ability to understand the intentions and perceptions of various agents in a story who interact with respect to some goal or problem. Reasoning about the state of mind of another person, real or fictional, has been referred to as Theory of Mind processing. While Theory of Mind Processing was first postulated prior to the existence of neuroimaging research, fMRI studies make it possible to characterize this processing in some detail. We propose that narrative comprehension makes use of some of the neural substrate of Theory of Mind reasoning, evoking what is referred to as a protagonist perspective network. The main cortical components of this protagonist-based network are the dorsomedial prefrontal cortex and the right temporo-parietal junction. The article discusses how these two cortical centers interact in narrative comprehension but still play distinguishable roles, and how the interaction between the two centers is disrupted in individuals with autism.

PMID: 19809575 [PubMed - as supplied by publisher]

Decreased Left Posterior Insular Activity during Auditory Language in Autism.

AJNR Am J Neuroradiol. 2009 Sep 12;

Authors: Anderson JS, Lange N, Froehlich A, Dubray MB, Druzgal TJ, Froimowitz MP, Alexander AL, Bigler ED, Lainhart JE

BACKGROUND AND PURPOSE: Individuals with autism spectrum disorders often exhibit atypical language patterns, including delay of speech onset, literal speech interpretation, and poor recognition of social and emotional cues in speech. We acquired functional MR images during an auditory language task to evaluate systematic differences in language-network activation between control and high-functioning autistic populations. MATERIALS AND METHODS: Forty-one right-handed male subjects (26 high-functioning autistic subjects, 15 controls) were studied by using an auditory phrase-recognition task, and areas of differential activation between groups were identified. Hand preference, verbal intelligence quotient (IQ), age, and language-function testing were included as covariables in the analysis. RESULTS: Control and autistic subjects showed similar language-activation networks, with 2 notable differences. Control subjects showed significantly increased activation in the left posterior insula compared with autistic subjects (P < .05, false discovery rate), and autistic subjects showed increased bilaterality of receptive language compared with control subjects. Higher receptive-language scores on standardized testing were associated with greater activation of the posterior aspect of the left Wernicke area. A higher verbal IQ was associated with greater activation of the bilateral Broca area and involvement of the prefrontal cortex and lateral premotor cortex. CONCLUSIONS: Control subjects showed greater activation of the posterior insula during receptive language, which may correlate with impaired emotive processing of language in autism. Subjects with autism showed greater bilateral activation of receptive-language areas, which was out of proportion to the differences in hand preference in autism and control populations.

PMID: 19749222 [PubMed - as supplied by publisher]

Healthcare for children with autism: the Autism Treatment Network.

Curr Opin Pediatr. 2009 Sep 9;

Authors: Coury D, Jones NE, Klatka K, Winklosky B, Perrin JM

PURPOSE OF REVIEW: Autism spectrum disorders (ASDs) are a group of a neurodevelopmental disorders affecting social, communicative, and behavioral functioning. ASD is a heterogeneous group of disorders, often accompanied by associated medical issues. Thus, the development of effective treatments is a complex task requiring consideration of diverse etiologic and phenotypic characteristics. Recent attention to the diagnosis and treatment of medical conditions in ASD children has led to the formation of a new international collaboration to improve autism care, the Autism Treatment Network (ATN). RECENT FINDINGS: Numerous studies have highlighted the high prevalence of gastrointestinal and sleep disorders among ASD children. Problems in communication - including being nonverbal - make the diagnosis and treatment of these conditions more difficult. Although a number of studies suggest links between neurologic impairments and gastrointestinal dysfunction and disordered sleep, these relationships remain unproven. Recent work by the ATN has begun the development of clinical guidelines in these areas, based on clinical consensus, adapting the model developed by the Cystic Fibrosis Foundation. New funding has also supported the network's development of a robust clinical research program focused on improving the physical health and care of children with ASD. These efforts promise more systematic and consistent approaches to diagnosis and treatment of these conditions. SUMMARY: Improved understanding of the underlying pathology of ASD and associated conditions, and the development of a common purpose across multiple treating sites, can improve the consistent and coordinated healthcare of children with autism.

PMID: 19745738 [PubMed - as supplied by publisher]

Schizophrenia.

Lancet. 2009 Aug 22;374(9690):635-45

Authors: van Os J, Kapur S

Schizophrenia is still one of the most mysterious and costliest mental disorders in terms of human suffering and societal expenditure. Here, we focus on the key developments in biology, epidemiology, and pharmacology of schizophrenia and provide a syndromal framework in which these aspects can be understood together. Symptoms typically emerge in adolescence and early adulthood. The incidence of the disorder varies greatly across places and migrant groups, as do symptoms, course, and treatment response across individuals. Genetic vulnerability is shared in part with bipolar disorder and recent molecular genetic findings also indicate an overlap with developmental disorders such as autism. The diagnosis of schizophrenia is associated with demonstrable alterations in brain structure and changes in dopamine neurotransmission, the latter being directly related to hallucinations and delusions. Pharmacological treatments, which block the dopamine system, are effective for delusions and hallucinations but less so for disabling cognitive and motivational impairments. Specific vocational and psychological interventions, in combination with antipsychotic medication in a context of community-case management, can improve functional outcome but are not widely available. 100 years after being so named, research is beginning to understand the biological mechanisms underlying the symptoms of schizophrenia and the psychosocial factors that moderate their expression. Although current treatments provide control rather than cure, long-term hospitalisation is not required and prognosis is better than traditionally assumed.

PMID: 19700006 [PubMed - indexed for MEDLINE]

Neuroimaging of the Functional and Structural Networks Underlying Visuospatial versus Linguistic Reasoning in High-Functioning Autism.

Neuropsychologia. 2009 Aug 18;

Authors: Sahyoun CP, Belliveau JW, Soulières I, Schwartz S, Mody M

High-functioning individuals with autism have been found to favor visuospatial processing in the face of typically poor language abilities. We aimed to examine the neurobiological basis of this difference using functional magnetic resonance imaging and diffusion tensor imaging. We compared 12 children with high functioning autism (HFA) to 12 age- and IQ-matched typically developing controls (CTRL) on a pictorial reasoning paradigm under three conditions: V, requiring visuospatial processing, S, requiring language (i.e. semantic) processing, and V+S, a hybrid condition in which language use could facilitate visuospatial transformations. Activated areas in the brain were chosen as endpoints for probabilistic diffusion tractography to examine tract integrity (FA) within the structural network underlying the activation patterns. The two groups showed similar networks, with linguistic processing activating inferior frontal, superior and middle temporal, ventral visual, and temporo-parietal areas, whereas visuospatial processing activated occipital and inferior parietal cortices. However, HFA appeared to activate occipito-parietal and ventral temporal areas, whereas CTRL relied more on frontal and temporal language regions. The increased reliance on visuospatial abilities in HFA was supported by intact connections between the inferior parietal and the ventral temporal ROIs. In contrast, the inferior frontal region showed reduced connectivity to ventral temporal and middle temporal areas in this group, reflecting impaired activation of frontal language areas in autism. The HFA group's engagement of posterior brain regions along with its weak connections to frontal language areas suggest support for a reliance on visual mediation in autism, even in tasks of higher cognition.

PMID: 19698726 [PubMed - as supplied by publisher]

Straight talk with...James Ironside. [Interviewed by Jon Evans].

Nat Med. 2009 Aug;15(8):834-5

Authors: Ironside J

Would you entrust your brain to a bank? Well, many people do after they die, and such brain banks-often funded by government agencies or disease charities-are essential for neuroscience research. They collect and store the healthy and diseased brain specimens that neuroscientists need to explore neurological disorders such as Alzheimer's disease, schizophrenia and autism. Each brain bank typically has a limited supply of samples and tends to operate fairly independently. This means that researchers often have to trawl through numerous brain banks to find their desired specimens. Furthermore, there is a general shortage of brain samples. To help resolve these issues in the UK, James Ironside, professor of clinical neuropathology at the University of Edinburgh, was appointed in June as the director of the new UK Brain Banks Network. An expert in human prion diseases, particularly Creutzfeldt-Jakob disease (CJD), Ironside knows all about brain banks. He established the Brain and Tissue Bank at the UK's National CJD Surveillance Unit and is involved in the Sudden Death Brain and Tissue Bank at the University of Edinburgh. Jon Evans recently caught up with Ironside to discuss his new leadership position and how the brain network will benefit neuroscience research.

PMID: 19661981 [PubMed - in process]

Calcium signaling and the development of specific neuronal connections.

Prog Brain Res. 2009;175:443-52

Authors: Lohmann C

During the development of the brain, synaptic connections between nerve cells are being established with remarkable specificity. This is achieved by a series of steps: first, axons grow to their terminal areas. Second, axons and dendrites contact each other and select among potential synaptic partners. Third, after synapses have become functional, the fine-tuning of synaptic connections optimizes emerging networks to perform their specific functions. Here, I summarize the evidence for a central role of intracellular calcium signaling in all three stages of the development of specific synaptic connections. In particular, calcium signaling has the capacity to integrate information from a wide array of extracellular factors that are known to regulate neuronal development, such as molecular cues or neuronal activity. Calcium signaling, in turn, directs structural as well as functional adaptations in individual neurons that underlie the establishment of synaptic specificity. Importantly, evidence is accumulating that errors in calcium-dependent network maturation are associated with neurodevelopmental disorders. Therefore, understanding the role of calcium in setting up brain networks may not only advance our insights into mechanisms of normal brain development, but also help identifying the causes of diseases such as autism or mental retardation.

PMID: 19660672 [PubMed - in process]

Development of large-scale functional brain networks in children.

PLoS Biol. 2009 Jul;7(7):e1000157

Authors: Supekar K, Musen M, Menon V

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

PMID: 19621066 [PubMed - in process]

Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults.

Am J Psychiatry. 2009 Aug;166(8):891-9

Authors: Di Martino A, Shehzad Z, Kelly C, Roy AK, Gee DG, Uddin LQ, Gotimer K, Klein DF, Castellanos FX, Milham MP

OBJECTIVE: The Social Responsiveness Scale-Adult Version (SRS-A) measures autistic traits that are continuously distributed in the general population. Based on increased recognition of the dimensional nature of autistic traits, the authors examined the neural correlates of these traits in neurotypical individuals using the SRS-A and established a novel approach to assessing the neural basis of autistic characteristics, attempting to directly relate SRS-A scores to patterns of functional connectivity observed in the pregenual anterior cingulate cortex, a region commonly implicated in social cognition. METHOD: Resting state functional magnetic resonance imaging scans were collected for 25 neurotypical adults. All participants provided SRS-A ratings completed by an informant who had observed them in natural social settings. Whole brain-corrected connectivity analyses were then conducted using SRS-A scores as a covariate of interest. RESULTS: Across participants, a significant negative relationship between SRS-A scores and the functional connectivity of the pregenual anterior cingulate cortex with the anterior portion of the mid-insula was found. Specifically, low levels of autistic traits were observed when a substantial portion of the anterior mid-insula showed positive connectivity with the pregenual anterior cingulate cortex. In contrast, elevated levels of autistic traits were associated with negative connectivity between these two regions. CONCLUSIONS: Resting state functional connectivity of the pregenual anterior cingulate cortex-insula social network was related to autistic traits in neurotypical adults. Application of this approach in samples with autism spectrum disorders is needed to confirm whether this circuit is dimensionally related to the severity of autistic traits in clinical populations.

PMID: 19605539 [PubMed - indexed for MEDLINE]

A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment.

J Neurosci. 2009 Jul 8;29(27):8752-63

Authors: Price MG, Yoo JW, Burgess DL, Deng F, Hrachovy RA, Frost JD, Noebels JL

Infantile spasms syndrome (ISS) is a catastrophic pediatric epilepsy with motor spasms, persistent seizures, mental retardation, and in some cases, autism. One of its monogenic causes is an insertion mutation [c.304ins (GCG)(7)] on the X chromosome, expanding the first polyalanine tract of the interneuron-specific transcription factor Aristaless-related homeobox (ARX) from 16 to 23 alanine codons. Null mutation of the Arx gene impairs GABA and cholinergic interneuronal migration but results in a neonatal lethal phenotype. We developed the first viable genetic mouse model of ISS that spontaneously recapitulates salient phenotypic features of the human triplet repeat expansion mutation. Arx((GCG)10+7) ("Arx plus 7") pups display abnormal spasm-like myoclonus and other key EEG features, including multifocal spikes, electrodecremental episodes, and spontaneous seizures persisting into maturity. The neurobehavioral profile of Arx mutants was remarkable for lowered anxiety, impaired associative learning, and abnormal social interaction. Laminar decreases of Arx+ cortical interneurons and a selective reduction of calbindin-, but not parvalbumin- or calretinin-expressing interneurons in neocortical layers and hippocampus indicate that specific classes of synaptic inhibition are missing from the adult forebrain, providing a basis for the seizures and cognitive disorder. A significant reduction of calbindin-, NPY (neuropeptide Y)-expressing, and cholinergic interneurons in the mutant striatum suggest that dysinhibition within this network may contribute to the dyskinetic motor spasms. This mouse model narrows the range of critical pathogenic elements within brain inhibitory networks essential to recreate this complex neurodevelopmental syndrome.

PMID: 19587282 [PubMed - indexed for MEDLINE]