Hurvitz Brain Sciences Research

Brain sciences scientists are studying mood disorders such as depression, anxiety and bipolar disorder from four main perspectives:

• Phenomenological
• Biological
• Psychopharmacological
• Cognitive behavioural

Unique to this program is our focus on people across the lifespan. We are working to improve the treatment of mood disorders for teenagers, adults and the elderly through population health initiatives, clinical trials and pharmacogenetics.

Population health initiatives ask questions such as the following:

• How common is seasonal bipolar disorder in Ontario?
• What are the trends in prescribing patterns for bipolar disorder in the elderly?
• What is the effect of antidepressant use on hospitalizations across Ontario? (a collaboration with the Institutes for Clinical Evaluative Sciences)

Example projects

• A clinical trial investigating which medication is most effective for bipolar disorder
• A utilization trial looking at how often antidepressants are used
• Probing the possibility that there is a genetic predictor able to specify who will respond to specific medications

Across all of these areas of investigation, our research findings are having an impact on the quality of treatment and the quality of life for patients with mood disorders. These results are receiving considerable national and international interest.

Just recently, scientists in the mood disorders program published the first findings from the Wireless Mood Telemetry Project, an 18-month pilot study that used wireless technology in real-time to track and map the moods of people with and without bipolar disorder. The twice-daily ratings collected were used to create a massive database that is now serving as an invaluable research resource.

Neuronal repair in the brains of Alzheimer’s patients

Scientist Dr. Isabelle Aubert is working to induce neuronal repair in the brains of Alzheimer’s patients using gene, cell and pharmacological therapeutic approaches.

Dr. Aubert’s research interests are in brain development, adult neurogenesis and regeneration.

Treating hydrocephalus

A laboratory team is performing physiological studies using novel mathematical models and new surgical intervention procedures. They are also testing imaging techniques to identify relevant absorption pathways.

Achievements to date include:

• Quantifying the importance of the lymphatic system in transporting CSF
• Developing new concepts about CSF absorption and the role of the relevant absorption pathways
• “Rewriting” the textbook on CSF physiology

The research study focused on the causes and treatments of stroke and dementia, or cognitive impairment, is comprehensive and adopts a variety of methods.

We are combining clinical, neurophysiological, neurocognitive and neuroimaging analyses to understand the processes of recovery and decline in stroke and dementia, which are the two leading neurological disorders that are challenging a rapidly aging population.

• Senior scientist Dr. Sandra Black is developing clinical and neuroimaging tools to detect dementia as early as possible, to aid differential diagnosis and to monitor disease progression and response to therapy.
• Dr. Black is also a leading clinical trialist for treatment of Alzheimer’s disease (AD). She is involved in working to bring disease-modifying therapies that aim to change the course of this devastating disease. Her lab group is particularly interested in the interactions of Alzheimer’s and cerebrovascular disease.
• Dr. David Gladstone leads clinical trials in stroke recovery and stroke prevention.
• Dr. Greg Stanisz focuses on advanced imaging techniques for understanding brain white matter. He uses imaging methods to monitor reparative effects of stem cells in rodent models of stroke.

Being able to use functional magnetic resonance imaging (fMRI) to assess patients’ brain activity as they recover from stroke may help to predict outcomes and pinpoint where brain functions happen. This could then help with the early detection of conditions like AD. It could also help with targeting and monitoring response to treatments for these impairments.

So far, findings have led to the classification of useful signs to detect and differentiate AD from normal aging and other dementias. They have also mapped brain changes in people recovering from stroke. Their

Brain-behaviour correlates in disorders

Dr. Anthony Feinstein and his team of researchers in neuropsychiatry are investigating brain-behaviour correlates in disorders such as traumatic brain injury (TBI), multiple sclerosis and conversion disorder (formerly known as hysteria). Another area of investigation is post-traumatic stress disorder, funded in part by organizations like the BBC and CNN, which are interested in the effects of war reporting on journalists.

Traumatic Brain Injury Clinic

The Traumatic Brain Injury Clinic, which is unique in Canada, has a large database of scans from magnetic resonance imaging (MRI) and single photon computerized emission tomography. These scans from more than 1,000 people contain a wealth of information to do longitudinal neuroimaging studies. One part of the database is devoted exclusively to studying head injury in the elderly.

So far, research on TBI has defined the following:

• prevalence of mood disorders in mild TBI
• predictors of poor outcome in mild TBI
• link between mood and cognition
• role of litigation in determining outcome

Scientists are now trying to create new therapies to improve the outcomes of patients with mild to moderate TBI.

The Geriatric Psychopharmacology Research Group, which includes researchers Dr. Krista Lanctôt (PI), Damien Gallagher (QI) and Giovanni Marotta (QI), is trying to optimize the management of neuropsychiatric symptoms associated with illness, which include apathy, agitation and cognitive changes. These are common consequences of many brain disorders, such as mild cognitive impairment, vascular mild cognitive impairment, CADASIL, Alzheimer’s disease and vascular dementia.

Our Group focuses on:

• the underlying neurobiology of neuropsychiatric symptoms
• precision interventions
• using novel drugs or repurposing existing drugs for new indications
• identifying and managing modifiable risk factors to prevent cognitive decline.

This group includes a multidisciplinary team of health care researchers. The group’s main research focus is to understand the neuropsychological changes involved in aging and the implications of these changes for dementia prediction, functioning in the community, response to drug treatment and care provision.

The team has demonstrated the utility of neuropsychological tests in the prediction of Alzheimer’s disease (AD) 10 years prior to its onset and are currently examining disease prediction after 15-years follow-up.

Another research focus is the role of estradiol on cognitive and behavioural changes in younger and older postmenopausal women. The group has recently completed a randomized controlled trial (RCT) of estrogen therapy and its effects on delayed verbal recall. Investigations into sex differences in health care utilization and factors involved in hot flashes, lifestyle and mood in recently post-menopausal women are also underway.

We are also conducting an ongoing large scale study of over 350 cognitively impaired seniors living alone in the community to examine the neuropsychological, behavioural, medical and social determinants of safety and emergency room use by these seniors.

Future studies include computer-assisted cognitive assessment in family medicine.