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Neurosciences & Mental Health


Congratulations to Dr. Jennifer Crosbie (with Co-investigator Dr. Russell Schachar), Dr. George Ibrahim (with Co-investigator Dr. Elizabeth Pang) and Dr. Lu-Yang Wang who have all been successful in obtaining a CIHR Project grant in the latest competition. Details of each award are below:

Predicting seizure responsiveness to neuromodulation using connectomic profiling  
PI: Dr. George Ibrahim; Co-PI: Dr. Elizabeth Pang

Epilepsy is the most common serious neurological condition that affects children. Active epilepsy interferes with normal childhood development, leading to disability and diminished quality of life. One-third of children will continue to have seizures despite the best available medications and therefore surgical treatments are increasingly utilized to reduce seizure frequency and mitigate the burden of the illness. 

For the most severely affected children, vagus nerve stimulation (VNS) offers hope of seizure control. An electrical nerve stimulator is attached to the vagus nerve at the neck and an implanted battery delivers continuous electrical stimulation that ascends to the brain, rendering the brain less susceptible to seizures. At present, however, only a minority of children implanted with VNS achieve meaningful reduction in seizures. There are no pre-operative means to identify those who will and will not respond to treatment. This lack of knowledge unnecessarily subjects some children to the risks of surgery and also deprives others, who would be better candidates from potential benefit. Because of the high cost of VNS, this also imposes a significant burden on the Canadian healthcare system. 

Using multiple, complementary advanced neuroimaging techniques, we will study how the connectivity of the brain circuits that mediate the effects of VNS differ between those who do and do not respond to treatment and compare them to typically-developing children. Findings from these multiple modalities will be used to train a machine learning algorithm to prospectively predict whether or not a child is likely to respond to VNS. For children and their families, these findings will mean less uncertainty about surgical outcomes. For healthcare providers, this will provide the means to deliver the correct treatment to the right child. For the Canadian healthcare system, this will translate into better allocation of limited healthcare resources.

Spit for Science 2: Genetic and environmental influences on behaviour and cognition in childhood neuropsychiatric disorders  
PI: Dr. Jennifer Crosbie; Co-PIs: Dr. Russell Schachar, Dr. Paul Arnold and Dr. Christie Burton

Many mental illnesses begin before age 18 and can have devastating effects throughout life. Three of the most common and impairing childhood-onset mental illnesses are attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD). Genes play an important role in these disorders but the specific genes are unclear. 

Spit for Science 2 (S2) continues the work of the Spit for Science (S1) by using alternative approaches to identify risk genes for childhood-mental illness. Instead of focusing on clinical diagnoses, which are complex and vary considerably from person to person, we are examining behavioural (e.g., inattention) and cognitive traits (executive functions - how you control behaviour to reach your goals) linked to the disorders and that cut across disorders. Patients are at the extreme of these traits but these traits vary widely in the population (attentive to inattentive). We will also examine how environmental factors like air pollution and marginalization affect how genes influence traits. 

To understand the genetics of mental illness in youth, we will recruit 30,000 children and adolescents from the Ontario Science Centre. They will provide DNA via spit, mental health trait information and complete an executive function cognitive task (Stop-Signal Task). Environmental risk data will be extracted from postal codes. Combining S2 and S1 data will create the largest paediatric mental health genetic sample in Canada providing sufficient statistical power to identify genetic signals. We will use a range of cutting-edge genetic methods to identify and validate genetic risk variants for these traits, understand which genetic risk are unique and shared across traits and disorders and test gene by environment interactions. We hope to identify novel genes involved in childhood mental illness which could potentially lead to early detection, better treatments and improved treatment-outcomes for Canadian youth.

Targeting a novel molecular locus for pharmacological and genetic rescue of Fragile X syndrome   
PI: Dr. Lu-Yang Wang

Fragile X syndrome (FXS) is a syndromic form of autism spectrum disorder (ASD), characterized by hyperactivity, seizures, intellectual disability, language and communication deficits, and other autistic behaviors. The syndrome is caused by a trinucleotide repeat expansion in the X-linked FMR1 gene, resulting in a drastic down-regulation of the mRNA binding protein, namely Fragile X Mental Retardation Protein, leading to neurodevelopmental deficits of the brain. This project will build upon our recent discovery of a novel interaction between FMRP and potassium channels that regulate inhibition, and develop innovative genetic and small organic molecules to target this locus, ultimately rectifying autistic behavior in FXS and potentially other types of ASD.

Psychiatric disorders share an underlying genetic basis, says landmark paper with U of T research

Nine researchers from the University of Toronto's Faculty of Medicine contributed to a major international study, published in the journal Science, showing the underlying genetic similarities between mental illnesses like schizophrenia and bipolar disorder. Read the full story here