"rTMS for Executive Function Deficits in Autism Spectrum Disorder"
This rigorous study will evaluate whether repetitive transcranial magnetic stimulation (rTMS) treatment can improve deficit in executive functions in older adolescents and young adults (ages 16 to 25) with Autism Spectrum Disorder (ASD), by comparing performance before and after treatment. Participants in our study will also undergo non-invasive brain scanning before and immediately after our four-week rTMS trial to see if their brain structure in particular regions, which are important for executive function abilities, has changed with treatment. This information will help us to understand how rTMS treatment works to improve executive function abilities in people with ASD and could signal a new treatment to improve everyday functioning.
"Predictors of Mental Health Outcomes in High-Risk Siblings of Children with Autism Spectrum Disorder: From Infancy to Middle Childhood"
Autism Spectrum Disorder (ASD) is a heritable and lifelong neurodevelopmental disorder that's characterized by social-communicative impairment and restricted and repetitive behaviour. ASD affects 1% to 1.5% of school-aged children, which translates to about 30,000 children in Ontario (100,000 in Canada). More than 80% of children and youth with ASD also suffer from other mental health problems such as anxiety, depression and Attention Deficit/Hyperactivity Disorder (ADHD). This study has one main objective: to identify differences very early in development that can help us predict which children will have mental health challenges when they get older (in particular, with anxiety and ADHD). Building an understanding of the earliest signs of these disorders may help us design strategies for early detection and intervention. By providing intervention very early in development, our hope is to prevent the poor outcomes that are common in this high-risk group.
“Targeting PTP1B to treat schizophrenia”
Schizophrenia is a debilitating mental disorder that affects young adults and that can lead to cognitive decline in later years. It is characterized by social isolation and a number of symptoms including auditory hallucinations, false beliefs, and often anxiety and depression. It has been proposed that infection in early development combined with genetic risk may lead to developing schizophrenia later in life. There is also growing evidence from clinical and animal studies that metabolic defects may exacerbate or even underlie defects in neural circuits in patients with schizophrenia.
“Responsiveness to Infant Cues in Postpartum Depression and Non-Depressed Mothers: Functional Neural Correlates and their Relation to Behavior”
This proposal describes a study that follows on our initial proposal that was funded by the OMHF for two years. The publications coming out of that proposal focused on the amygdala (AMY) as a mediator of emotion leads to our present proposal, which focuses on mothers’ appraisal of infant and non-infant cues as rewarding, and on neural responses in the mesolimbic (nucleus accubmens, NAC) reward system. This proposal is unique in that it explores three networks together - the maternal, emotion and reward brain networks - and their effects on one another in mothers and non-mothers who have experienced varying degrees of depression.
“The neurotrophic cytokine, erythropoietin, as a novel antidepressant"
Recent research on the causes of depression have begun to move away from the traditional notion that the disorder stems simply from reduced levels of the brain neurotransmitters, serotonin, norepinephrine and dopamine. Recently accumulating data suggests that depression might have as its basis actual structural changes in the brain circuits that control emotions. Evidence points to structural changes in two key brain regions (the hippocampus and prefrontal cortex) that are important for interpreting social situations and are also critical for learning and memory, as well as for influencing emotional state. Furthermore, the drug ketamine has recently been shown to be rapidly effective in treating depressed patients who had been treatment-resistant. Its effectiveness has been suggested to occur as a result of rapid structural brain changes (increased number and branching of neuronal projections) and increased levels of brain growth factors [specifically, brain derived neurotrophic factor (BDNF)] that support such structural alterations.
“Examining the Association between Lithium Levels and Poor Renal Outcomes in Older Lithium Users: A Population-Based Longitudinal Cohort Study”
Lithium carbonate is a mood stabilizer, and the gold-standard of treatment for bipolar disorders. One percent of all Ontarians (more than 15,000 people) use lithium; many more patients with bipolar disorder and depression could potentially benefit from its use. Patients with mood disorders are often prescribed a number of medications and spend decades with inadequately treated symptoms. Mood disorders can be burdensome illnesses to patients, their families, society and the health care system. Lithium is one of the most effective medications in bipolar disorder, with 30 to 40% of patients responding better to this medication than alternatives. However, concern about its potential to cause kidney disease prevents more widespread use, especially in older adults. Adding to this, older adults are already at increased risk for kidney disease from other medical conditions, and it is not yet known which blood lithium levels are associated with increased kidney disease in older adults.
“The use of food to soothe: The role of maternal depression in infant feeding practice and cardiometabolic risk”
This study examines a new conceptual framework to understand one way in which depression and risk for heart disease might be co-developed, or related early in life. We will study infants of mothers with depression and healthy mothers, as infants of mothers with depression are at high risk for developing depression themselves. This study will take place in the offices of a Toronto-based family physician and a pediatrician during regular well-child visits. We will compare infant growth and the risk factors of early heart disease (for example, blood pressure, blood sugar, insulin and lipids) of infants of mothers who are experiencing depression and those who are not. We will also investigate whether mothers with depression feed their infants differently than mothers not experiencing depression, and whether these feeding patterns might be related to the infant’s temperament and infant’s risk of overweight or obesity.
"The effects of neurodevelopmental exposure to the primary psychoactive component of marijuana, delta-9-tetrahydrocannabinol (THC)''
Our research program is focused on an issue of urgent concern to mental health care in Ontario. Recent epidemiological evidence has demonstrated that the use of cannabinoid drugs such as marijuana is increasing exponentially among Ontario youth. This is of particular concern given a wealth of clinical evidence showing that exposure to marijuana during critical periods of adolescent brain development may lead to serious mental health problems, including an increased risk of developing schizophrenia, in young adulthood.
"Amplifying empathy-related brain activity in youth with callous and unemotional traits"
This study aims to measure, using neuroimaging techniques, the capacity of subgroups of youths with conduct disorder with high and low levels of callous traits to use directed attention to distress and perspective-taking to increase their feelings of concern and sensitivity. The primary outcome measure will be activation levels of specific brain regions associated with emotion and empathy: the amygdala and ventromedial prefrontal cortex. Our central theory is that the subgroups of youths with conduct disorder will differ in their capacity to benefit from empathy-induction techniques as they view pictures that normally elicit feelings of concern. Whereas youths without callous traits will show a similar or increased capacity to experience empathy to distress-related stimuli relative to controls, those with callous traits will show a reduced capacity.
"Identification of the Neural Circuitry of Persistent Negative Symptoms in First Episode Schizophrenia"
Our work aims to identify how the brains of patients early in their first episode of schizophrenia with severe "negative symptoms" are different from the brains of patients with schizophrenia who do not have this same clinical picture and from the brains of healthy people without schizophrenia. We plan to use cutting-edge brain imaging approaches to understand these differences. One approach measures the thickness of parts of our brain, which can serve to tell us approximately how much brain tissue an individual might have in any given brain regions. The second approach tells us about the quality of the tissue that connects different brain regions, allowing these regions to communicate with each other.
"The Endocannabinoid system and risk for alcohol use disorder: A PET study with the novel Fatty Acid Amide Hydrolase radioligand [11C] CURB"
"Assessing Changes in Cerebral Perfusion and Neuropsychological Function in Response to Aerobic Exercise among Adolescents with versus without Bipolar Disorder"
"Prediction of psychosis in at-risk individuals using an event-related brain potential measure of conceptual relationship processing"
"Efficacy of a Group Cognitive Behaviour Therapy Program in the Treatment of Young Children with Social Anxiety Disorder and/or Selective Mutism: A Randomized Control Trial"
"Death by Suicide within a year after a Mental Health Related Emergency Department Visit or Hospital Admission: A Linkage Study of Adults in the Province of Ontario"
"Comorbid Eating Disorders and Posttraumatic Stress Disorder: Facilitating Full and Sustained Recovery Through Empirically-Based Concurrent Treatment"
"Decoding the Non-Coding Genome: Functional Annotation of Genetic Variation in Gene Regulatory Regions Contributing to Psychiatric Disorders"
"Beyond Silence: Comparing the impact of contact-based education with mental health literacy training on early intervention for healthcare workers with mental health issues"