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This newly established lab will focus on neurodevelopmental disorders and their trajectories across the lifespan. Embracing a truly interdisciplinary and developmental approach to understanding disorders across multiple levels of analysis, researchers will experience a range of innovative technologies designed to tease apart subtle pathways of function and dysfunction at the brain and cognitive levels (e.g. infra red eye tracking, novel experimental paradigms). A critical component of this lab is to chart BOTH typical and atypical developmental trajectories.
Lab members
Professor Kim Cornish, Director, kim.cornish@monash.edu
Dr Darren Hocking, Research Fellow, darren.hocking@monash.edu
Daniel Thomas, Lab Manager, dltho6@student.monash.edu
Claudine Kraan, PhD student, claudine.kraan@monash.edu
Tamara May, PhD student, tamara.may@monash.edu
Laura Bell, Honours student, lmbel6@student.monash.edu
>> PhD Scholarship Opportunities in Developmental Neuroscience
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Neurodevelopmental Disorders of interest include:
Fragile X Associated Disorders
Autism
Fragile X and Autism: A Complex Relationship
Williams syndrome
Attention Deficit/Hyperactivity Disorder
Fragile X Associated Disorders
Although fragile X syndrome results from changes to a single gene there is now widespread agreement that the condition has a broad spectrum of involvement that impacts those who carry the gene and those who have fragile X syndrome.
Fragile X syndrome: Fragile X syndrome was first described in 1943 by Martin and Bell (originally labelled the “Martin-Bell” syndrome) and is the world’s most common hereditary cause of developmental delay in males. Although still lacking consensus, recent estimates indicate a frequency of approximately 1 per 2,500. The condition is caused by the silencing of a single gene on the long arm of the X chromosome. The gene, named the Fragile X Mental Retardation Gene – 1 (FMR1), was identified in 1991 and is “turned off” in affected individuals. When this happens, a specific protein (FMRP) is not produced resulting in a unique constellation of strengths and difficulties that characterise fragile X children and adults across their lifespan. These can include:
- behaviour problems including anxiety, shyness, mood disorders, depression
- severe inattentive behaviours and hyperactivity similar to ADHD
- intellectual disability and language delay
- cognitive impairments in working memory
- distractibility and lack of inhibitory control
- autism-like characteristics leading to a diagnosis of autism spectrum disorder in approximately 40% of children.
- good visual memory for faces and meaningful material
Useful reading: Cornish, Scerif, & Karmiloff-Smith 2007, download pdf (204kb); Cornish, Turk, & Hagerman 2008, download pdf (148kb).
Fragile X Carriers: Recent estimates indicate that carriers of the fragile X syndrome (those individuals with a small change in their gene) are more common in the general population (approximately 1 in 250 females and 1 in 800 males) than those who are fully affected and so the frequency of the problems associated with being a carrier are more common than the problems associated with the full mutation- fragile X syndrome. In recent years a newly diagnosed neurodegenerative disorder has been discovered by Dr Randi Hagerman and her colleagues at the MIND Institute at UC Davis in the US and is known as Fragile X tremor and ataxia syndrome (FXTAS). FXTAS does not occur in fully affected individuals and rarely in female carriers.
The Fragile X-associated Tremor/Ataxia Syndrome (FXTAS)
When grandfathers of children with fragile X were evaluated a consistent neurological disorder was discovered in a subgroup of these men that included both intention tremor and ataxia. Further research prompted by this discovery has revealed a range of other symptoms that include:
- psychiatric features including agitation, dysinhibition and anxiety
- neuropathy in the lower extremities (Berry-Kravis et al. 2007)
- cognitive deficits notably executive function and memory deficits (e.g. Grigsby et al 2006)
Useful reading: Cornish, Li et al. 2008, download pdf (244kb); Hay, 2008 download pdf (88kb); Cornish, Kogan et al 2009 download pdf (224kb); Cornish Turk & Hagerman 2008, download pdf (372kb); Kogan et al. 2008, download pdf (224kb); Cornish, Manly et al 2005.
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Autism
Autism is a complex neurodevelopmental disorder that has intrigued clinicians and researchers for decades. It was originally described by Kanner in 1943 and is characterized by a “triad of impairment” that includes a severe disruption in communication/language skills, impaired reciprocal social interactions and restricted/repetitive patterns of behavior, interests/routines. However, it is perhaps the clinical heterogeneity of this disorder that makes capturing the causal mechanism of autism so elusive. For example, there appear to be two causal pathways resulting in autistic behavior. The first has been labeled “idiopathic” in which autism presents independent of any other disorder. Idiopathic autism is found in familial clusters as identified by twin and family studies. The second is referred to as “syndromic autism” and occurs as part of a broader genetic phenotype such as fragile X syndrome or 22q11 DS. The idiopathic pathway has received considerable research interest and we provide below a snapshot of some of the exciting discoveries that have begun to isolate putative susceptibility genes for autism. The second syndromic pathway has received less focus but is an emerging area that is likely to generate considerable interest in the next few years. What remains unknown is the extent to which the different autism pathways, presumably resulting from different etiologies, converge or diverge across development.
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Fragile X and Autism: A Complex Relationship
There are currently very few single-gene disorders for which there is a certainty of the involvement of autism; fragile X is one. As a single-gene disorder, fragile X offers an interesting genetic model to explore the functions of FMRP regulation and the repercussions of its loss in early brain development. Commonalities across core social and language domains define the link between fragile X and autism, and it therefore seems highly plausible that similar neurobiological mechanisms are affected in both disorders.
Useful reading: Cornish, Turk & Levitas 2007, download pdf (724kb)
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Williams syndrome
Williams syndrome, also known as Williams-Beuren syndrome, was initially identified independently by Williams and Beuren in 1961. Until quite recently, it was assumed to be a rare disorder – 1 in 15,000-20,000, but one recent estimate indicates the frequency at approximately 1 in 7,500. The disorder is not usually hereditary and results from the deletion of approximately 25-30 genes on the long arm of chromosome 7.
Intellectual impairment, although variable in severity, is a core characteristic of almost all children with Williams syndrome but perhaps most salient is their distinctive behavioural and cognitive profile that can include:
- obsessive behaviour and high degrees of anxiety
- extreme friendliness and sociability, with an excessive display of empathy
- hyperactivity, distractibility, inattention and lack of persistence
- impaired visual-spatial working memory
- relative strength in perceptual attention skills
- relative strength in face processing skills
In my own research we have compared the attention profiles of toddlers and children with Williams syndrome and fragile X syndrome across their respective trajectories to establish when in development skills converge and diverge from each other and typically developing peers. [Scerif, Cornish et al., download pdf (252kb) 2004; Cornish, Scerif & Karmiloff-Smith 2008, download pdf (204kb)]
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Attention Deficit/Hyperactivity Disorder
Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood psychiatric disorders and is characterized by a triad of clinical features: inattention, impulsivity, and hyperactivity. Consequently, children with ADHD are at greater risk for low academic achievement, substance abuse and anti-social behaviour/delinquency in adolescence. Impairments in attentional control may lie at the core of this condition and these are likely to interact with working memory difficulties across development. The search for susceptibility genes (e.g. DAT1, DRD4; COMT; SNAP-25) that might contribute to the ADHD phenotype has been the subject of intense investigation and it is now widely accepted that several genes may be implicated in ADHD.
In this research we have been looking at the association between the dopamine transporter gene (DAT1) and ADHD symptoms and response inhibition in a general population of schoolchildren. See Cornish, Manly et al., (2005) Association of the dopamine transporter (DAT1) 10/10-repeat genotype with ADHD symptoms and response inhibition in a general population sample. Molecular Psychiatry. Jul;10(7):686-98 and Cornish, Wilding and Hollis (2008) Visual search performance in children rated as good or poor attenders: the differential impact of DAT1 genotype, IQ, and chronological age. Neuropsychology.Mar;22(2):217-25.
The above syndrome “snapshots” were adapted from our new book “ Attention, Genes and Developmental Disorders” (Cornish & Wilding) to be published by Oxford University Press, New York
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