Schizophrenia Research Program

Section Head

Z. Jeff Daskalakis, MD, PhD, FRCP

Contact

Dr. Daskalakis
Schizophrenia Program
Centre for Addiction and Mental Health
250 College Street
Toronto, Ontario M5T 1R8
(416) 535-8501, ext. 4319
jeff_daskalakis@camh.net

Research Objective

The Schizophrenia Research Program is devoted to understanding the biological causes of schizophrenia and those interventions that offer optimal care to persons with this illness. The aim of this research is to improve our assessment, diagnosis, and treatment of schizophrenia and ultimately, the quality of life for affected persons.

Summary of Activities

Schizophrenia is a neurodevelopmental disorder that is a result of complex genetic and psychosocial interactions. It adversely affects patients’ functional capabilities (e.g., social, vocational) and constitutes a surprisingly large sector of healthcare and social services spending. Consistent with the complexity of schizophrenia, our research efforts to understand and improve treatment for this illness have ranged from studies of molecular biology to community-based policy initiatives. Many of these activities can be captured under the following four categories:

Neurbiological abnormalities associated with psychosis

Our scientists have leveraged several different neuroimaging techniques to show that patients with schizophrenia have a number of brain deficiencies including: reduced grey matter and white matter integrity; abnormal neural suppression by GABAergic interneurons; reduced hippocampal activity during memory tasks; reduced neural activity in the cortical pathway devoted to goal-directed action; and poor activation of the nucleus accumbens while associating a neutral event with a noxious consequence such as electric shock.

Similarly, genetic studies in our Program have uncovered several important candidate genes and led to a genetic model of schizophrenia based on our observations of an increased liability for the illness among patients with 22q11 Deletion Syndrome, a chromosomal abnormality.

Mechanisms of antipsychotic activity and efficacy

Our Positron Emission Tomography (PET) team discovered that differences in the therapeutic efficacy and side effects associated with different classes of antipsychotic medications are linked to the rapidity with which each drug dissociates itself from dopamine receptors. PET technology has also been integral to the study of new radioligands to measure the pharmacological integrity of other neurotransmitters, including the serotonin system.

Side effects of antipsychotic treatment

Despite the effectiveness of antipsychotic medications, they also induce some unwanted side effects. By administering small, single doses of these medications to healthy volunteers, researchers in our program have uncovered specific adverse effects on mood and cognition. Similarly, our clinician scientists have partnered with nutrition experts at the University of Toronto to better understand how antipsychotic medications result in metabolic abnormalities, which can potentially lead to weight gain and diabetes.

Optimal treatments for early psychosis

Our scientists are at the cutting edge of examining innovations for treating early psychosis including the benefits of home intervention with a mobile treatment team. The usefulness of Cognitive Behavioural Treatment and the efficacy of low-dose antipsychotic medication are also being evaluated in this community-based research project. A dedicated clinic has been established to study teenagers and young adults at ultra-high risk for developing psychosis.

 

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