Noradrenergic and Dopaminergic Neurotransmission in Schizophrenia Patients at High Risk for Suicide

Suicide represents a major public health problem, with a worldwide rate of 10.7 per 100,000 people, claiming over 788,000 lives per year. This investigation aims to analyze the neuromelanin signal in the brains of people with schizophrenia (SCZ) at high risk and low risk of suicide using neuromelanin-sensitive magnetic resonance imaging (NM-MRI). This study will examine whether NM-MRI is a practical, non-invasive approach to estimate suicide risk.

Lifetime suicide risk has been estimated to be 5-7% in patients with schizophrenia (SCZ) and related psychoses. However, there are no biomarkers currently available to distinguish between multiple suicide attempters (high risk for suicide) and non-suicidal ideators (low risk for suicide) in the SCZ population. Neuromelanin (NM) is a byproduct of catecholamine metabolism and thereby proxy measure of dopamine and noradrenaline synthesis. NM is typically increased in the substantia nigra (midbrain) of patients with SCZ. Therefore, the objective of this study is to quantify the NM in the substantia nigra (SN) and Locus Ceruleous (LC) using a neuromelanin-sensitive magnetic resonance imaging (NM-MRI) to highlight the differences between individuals at high risk (HR) versus low risk (LR) for suicide within the SCZ population. We will select 45 HR and 45 LR SCZ patients from an established clinical database at the Centre for Addiction and Mental Health (CAMH) for this case-control MRI study. The participants will be assessed to test whether NM levels in the SN and LC can differentiate these two groups using a NM-MRI protocol. NM level difference in SN and LC between HR and LR subjects will be assessed to generate a prediction algorithm to identify individuals at high risk for suicide.  This investigation will provide knowledge on a potential neuroimaging biomarker and determine whether NM-MRI is a practical approach for predicting suicidal behavior in SCZ.