Innovating Care and Discovery |New Treatments and Innovations

Using iTBS to Enhance Social Cognition in People with Psychosis 

This clinical trial, led by  Aristotle Voineskos and Daniel Blumberger, in young adults with early psychosis extends on our previous multisite collaboration investigating novel treatments for social cognitive deficits in psychosis.  The purpose of this research study is to investigate a new intervention option for people with psychosis between ages 18-39 and to determine if a form of repetitive transcranial magnetic stimulation (rTMS) known as intermittent theta burst stimulation (iTBS) produces change in brain regions that are involved in social skills. CAMH is one of three sites of a multi-centre trial funded by the Wellcome Trust, with identical protocols and procedures at each site in a single study that aims to randomize 100 participants total, of which 33-34 participants will be randomized across 4 years at CAMH

Examining a Digital Health Approach for Advancing Schizophrenia Illness Self-Management and Provider Engagement (A4i)

Dr. Sean Kidd is conducting a feasibility RCT funded by CIHR that is examining a digital health approach for schizophrenia illness self-management, App4Independence (A4i). A4i provides customized coping prompts, an auditory “hallucination detector”, peer-to-peer networking, and a portal that facilitates better provider engagement. This research will provide critical information in the development of this new technology to address a key problem in the field - how to enhance care in a resource-limited context where provider-patient contacts are brief, infrequent, and rely on in the moment recall and self-advocacy by patients. This work is at the forefront of international efforts to explore and validate digital health approaches for schizophrenia. Dr. Kidd has also, with a Discovery Fund award, developed a version of A4i for opioid addiction populations that will soon begin testing. 

Treatment of Negative Symptoms in Early Schizophrenia with Transcranial Direct Current Stimulation Coupled with Virtual Reality Training (NEST)

Negative symptoms, including the loss of motivation and reduced emotional expression, have emerged as critical symptoms in schizophrenia that lead to functional disability for affected individuals. Despite advances in treatment, there are no effective treatments for these negative symptoms, which ultimately hinders recovery for patients. To address this critical unmet therapeutic need, Dr. George Foussias is leading a study that aims too investigate the combination of transcranial direct current stimulation (tDCS) with virtual reality motivation training, to treat negative symptoms in schizophrenia. We anticipate the results of this study will provide the first evidence supporting the efficacy of this combined non-invasive brain stimulation and virtual reality treatment, both in terms of improving negative symptoms and community functioning, as well as brain functioning that supports motivated behaviour.

Effects of N-acetylcysteine (NAC) on psychosis-like symptoms and a neurophysiological biomarker of the clinical high risk state for schizophrenia 

Studies suggest that N-acetylcysteine (NAC), a natural health product that is an antioxidant precursor, is safe, well-tolerated, and reduces symptoms of schizophrenia, raising the possibility it may also improve symptoms in individuals who have not yet developed psychosis but are at clinical high risk (CHR) for schizophrenia.  Dr. Michael Kiang, with funding from the Canadian Institutes of Health Research, is leading a randomized, double-blind, placebo-controlled trial to test whether NAC is an effective treatment for symptoms in CHR youth, and if it can improve brainwave abnormalities that are seen in people with schizophrenia and in the CHR state. If so, these findings would provide a novel opportunity for early intervention and potential prevention of schizophrenia.

Identifying the Neurobiology of Depression in Schizophrenia Spectrum Disorders

Depressive symptoms are common in Schizophrenia Spectrum Disorders (SSDs), impacting suicidality, illness course, and quality of life. There are, however, limited effective treatment options for people with psychosis who also experience depressive symptoms. This large study, combining data from three studies conducted through the Slaight Centre at CAMH, uses functional brain imaging to uncover the specific brain circuitry linked to depressive symptoms in SSDs. Emerging results from this work has revealed that depressive symptoms are related to specific patterns of connectivity within the brain.  Leveraging data from a previous brain stimulation clinical trial at the Slaight Centre, improvements in connectivity in these brain circuits was linked to specific improvement in depressive symptoms.  These novel findings set the stage for a future brain stimulation trial, targeting this underlying brain circuitry, to formally assess a potential new treatment for depressive symptoms in individuals with SSDs.

Computational Assays for Individual Treatment Predictions in First Episode Psychosis

A key challenge in the treatment of early psychosis is the heterogeneity in treatment response across patients: despite similar initial symptoms, patients often show divergent symptom trajectories over time, and some symptoms persist in spite of treatment. Antipsychotic medication that targets either dopamine or acetylcholine receptors, or both neuromodulatory systems, is used to treat schizophrenia. However, there are no clinical tests to guide treatment and predict which individual patient will benefit from which type of pharmacological intervention. Consequently, treatment decisions rely on a trial-and-error process, which places a severe burden on patients. To overcome this impasse, this new project — led by Dr. Andreea Diaconescu, an Independent Scientist at the Krembil Centre for Neuroinformatics — introduces a neurocomputational approach for understanding the emergence of psychosis symptoms focusing on brain dopaminergic and cholinergic systems using reward and contextual learning paradigms combined with validated mathematical models of cortical computation. This study will investigate the clinical validity of this approach through a longitudinal study in first-episode psychosis (FEP) patients in the early stages of treatment initiation. Through a combination of computerized tasks and brain imaging during the time treatment is being started, coupled with neurocomputation, this study anticipates providing insights into the key cognitive and neurobiological causes of psychosis, and informing personalized treatment intervention strategies for youth and young adults experiencing a first episode of psychosis.