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Our Research Focus

Monash CADLAB

 Monash CADLAB

Monash CADLAB 

Monash CADLAB

The Developing Brain

The focus of the Cornish Lab is the developing brain. The brain goes through a remarkable journey across the lifespan from its start-state in the pre-natal period all the way through to late adulthood. A whirlwind of new research discoveries have helped shape our current understanding of how the brain develops and the constraints that shape later learning outcomes. In our lab, we focus on how genetics may serve to impact cognitive domains such as attention and motor. We study very young children as well as adolescents and adults using our own experimental paradigms that capture and observe developmental changes in real time.

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 weaknesses 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); Cornish, Cole et al., 2012, download pdf (373kb); Scerif, Longhi et al., 2012, download pdf (317kb).

Fragile X Carriers: Recent estimates indicate that carriers of fragile X syndrome (those individuals with a small change in the 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.

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 (148kb); Cornish, Manly et al. 2005.

Interview: What is Fragile X?

Project: Australian Fragile X Premutation Carrier Study 

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 severe disruption in communication/language skills, impaired reciprocal social interactions and restricted/repetitive patterns of behaviour, interests and 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 behaviour:

  • 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, with a number of 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 different autism pathways, presumably resulting from different etiologies, converge or diverge across development.

Useful reading: Sivaratnam, Cornish et al., 2012, download pdf (497kb); Rinehart, Cornish & Tonge, 2011 (Chapter, Biological basis of sex differences in psychopharmacology); Bertone, Hanck et al., 2010, download pdf (285kb).

Project: ASD Attention and Academics Study

Project: NAPS

Williams Syndrome

Williams syndrome, also known as William-Beuren syndrome, was initally 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 the 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
  • relative strength in language production

In our research, we have compared the attention profile 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.

Useful reading: Scerif, Cornish et al. 2004, download pdf (252kb); Cornish, Scerif & Karmiloff-Smith 2007, download pdf (204kb).

Project: Willams syndrome and Down syndrome Motor Study

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 a 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 dopamine transporter gene (DAT1) and ADHD symptoms and response inhibition in a general population of schoolchildren.

Useful reading: Cornish, Manly et al. 2005, download pdf (370kb); Cornish, Wilding, & Hollis 2008.

 

Future Directions

A core research interest of this newly established lab is fragile X syndrome (CORNISH, TURK & HAGERMAN 2008 and http://www.fragilex.org.au), the world’s most common hereditary cause of developmental delay. Arguing that fragile X should be viewed as “continuum” of clinical involvement we explore genetic-brain-neurocognitive pathways in both carriers of the condition (premutation status) and those with fragile X syndrome (full mutation status).

Below is an example of a research project that we invite potential students and fellows to be involved in.

  1. Identifying ADHD and autism phenotypes in genetic disorders such as fragile X syndrome and their early developmental trajectories

    Within this topic, we are focusing on the frequently observed heterogeneity within fragile X. Specifically exploring how early markers of autism and/or ADHD symptoms in this condition may help to identify the different pathways of cognitive and social outcomes that represent the fragile X phenotype. Beginning this exploration as early as possible after diagnosis will produce the greatest benefits in terms of development and timing of appropriate clinical and educational interventions. Furthermore by exploring the relation between so called “attention” genes and ADHD profiles we aim to elucidate the contribution of other genetic variations to the fragile X phenotype.

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