Clifford M Cassidy

Royal Ottawa Mental Health Centre

Following the development of magnetic resonance imaging (MRI) methods to assay the integrity of catecholamine nuclei, including the locus coeruleus (LC), there has been an effort to develop automated methods that can accurately segment this small structure in an automated manner to promote its widespread use and overcome limitations of manual segme...

Background: The integrity and function of catecholamine neurotransmitter systems can be assessed using neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. Purpose: To support future application of NM-MRI as...

Late-life depression (LLD) is a risk factor for age-dependent cognitive deterioration. Norepinephrine-related degeneration in the locus coeruleus (LC) may explain this link. To examine the LC norepinephrine system in vivo, we acquired neuromelanin-sensitive MRI (NM-MRI) in a sample of 48 participants, including 25 with LLD (18 women, age 68.08±5.41...

Background The integrity and function of catecholamine neurotransmitter systems can be assessed using MRI sequences often referred to as neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. To support such futu...

Perturbations in dopamine system function may increase risk of substance use disorder (SUD). We recently demonstrated that neuromelanin (NM) MRI signal in the substantia nigra, a non-invasive index of dopamine system function, is elevated in long term cocaine users (Cassidy et al., 2020). However, it is unclear whether elevated NM-MRI signal is lin...

Patients with schizophrenia have a high prevalence of cigarette smoking and respond poorly to conventional treatments, highlighting the need for new therapies. We conducted a mechanistic, proof-of-concept study using bilateral deep repetitive transcranial magnetic stimulation (dTMS) of insular and prefrontal cortices at high frequency, using the sp...

The clinical and pathophysiological correlates of locus coeruleus (LC) degeneration in Alzheimer’s disease (AD) could be clarified using a method to index LC integrity in vivo, neuromelanin-sensitive MRI (NM-MRI). We examined whether integrity of the LC-norepinephrine system, assessed with NM-MRI, is associated with stage of AD and with neuropsychi...

Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging...

The catecholamine neuromodulators dopamine and norepinephrine play key roles in cognition and psychiatric pathophysiology. Much of the evidence for this comes from human studies using positron emission tomography (PET), which allows direct, in vivo measurement of aspects of catecholamine function, such as synthesis or transmission. However, the inv...

Background: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a validated measure of neuromelanin concentration in the substantia nigra-ventral tegmental area (SN-VTA) complex and is a proxy measure of dopaminergic function with potential as a noninvasive biomarker. The development of generalizable biomarkers requires large-scale sampl...

Background Associative learning and memory processes, including the generalization of previously learned associations, may be altered in schizophrenia. Deficits in schizophrenia in stimulus generalization, one of the simpliest forms of memory, could interfere with the ability to efficiently categorize related, similar information, potentially leadi...

Background: Neuromelanin-sensitive MRI (NM-MRI) of the substantia nigra provides a noninvasive way to acquire an indirect measure of dopamine functioning. Despite the potential of NM-MRI as a candidate biomarker for dopaminergic pathology, studies about its reproducibility are sparse. Purpose: To assess the test-retest reproducibility of three c...

Late-life depression (LLD) is a prevalent and disabling condition in older adults that is often accompanied by slowed processing and gait speed. These symptoms are related to impaired dopamine function and sometimes remedied by levodopa (L-DOPA). In this study, we recruited 33 older adults with LLD to determine the association between a proxy measu...

In contrast to cardiac sympathetic activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (cholinergic) activity. A radioligand able to measure cardiac cholinergic activity would be an invaluable clinical and research tool since cholinergic dysfunction has been as...

Objective: Recent evidence supports the use of neuromelanin-sensitive MRI (NM-MRI) as a novel tool to investigate dopamine function in the human brain. The authors investigated the NM-MRI signal in individuals with cocaine use disorder, compared with age- and sex-matched control subjects, based on previous imaging studies showing that this disorde...

Fluctuating craving and stress contribute to opioid use disorder (OUD) treatment failure. However, we lack a complete understanding of these factors, particularly at the neural systems-level. Preclinical studies suggest the locus coeruleus norepinephrine (LC-NE) system is a candidate pathway through which stress and craving promote opioid reuse. Th...

Significance Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates in the substantia nigra (SN). Prior work has shown that NM-MRI provides a marker of SN integrity in Parkinson’s disease. Here, we show that it may additionally provide a marker of dopamine function...

The diagnosis of Parkinson’s disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies sugg...

Hallucinations, a cardinal feature of psychotic disorders such as schizophrenia, are known to depend on excessive striatal dopamine. However, an underlying cognitive mechanism linking dopamine dysregulation and the experience of hallucinatory percepts remains elusive. Bayesian models explain perception as an optimal combination of prior expectation...

Background: The current study uses neuromelanin-sensitive MRI (NM-MRI), a brief, noninvasive, imaging technique that has widely been used in Parkinson’s disease, to investigate signal changes in the substantial nigra of subjects at risk for psychosis which may reflect excess dopamine activity prior to the full onset of psychosis. Methods: We perfor...

Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) purports to detect the content of neuromelanin, a product of dopamine metabolism found in the neurons of substantia nigra (SN). Neuromelanin formation rescues neurons from toxicity caused by excess dopamine. NM-MRI has proven to be very effective at detecting neurodegeneration of dopamine n...

Importance: Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such...

Unlabelled: Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unk...

Most drugs of abuse lead to a general blunting of dopamine release in the chronic phase of dependence, which contributes to poor outcome. To test whether cannabis dependence is associated with a similar dopaminergic deficit, we examined striatal and extrastriatal dopamine release in severely cannabis-dependent participants (CD), free of any comorbi...

Background: Dysfunctional reward processing is present in individuals with schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction. Our objective was to identify a deficit in patients with SSD on response to rewarding stimuli and determine whether this deficit predicts cannabis use. Methods: We divided a group of patient...

Background: Despite the accumulation of evidence indicating negative consequences of cannabis use in schizophrenia, there has been little progress in reducing cannabis abuse in this population. It may be necessary to better characterize factors promoting cannabis use in order to tackle this problem. Dysfunctional reward processing is present in sch...

Deficits in incentive motivation are often present in both Schizophrenia Spectrum Disorders (SSD) and substance-use disorders. The current study aims to test whether the presence of such deficits confers vulnerability to cannabis use in individuals with SSD. SSD patients (n=35) and healthy controls (n=35) were each divided into a group with (n=20)...

The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first-episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation. We genotyped 2...

Objective: Our study examines the unique influence of social and family support on adherence to medication in a sample of patients treated for first-episode psychosis (FEP). Method: Social and family support using the Multidimensional Scale of Perceived Social Support and medication adherence (consensus of subjective and objective data) were eva...

Background Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known. Aims To comprehensively investigate the relationship between rs9960767 risk allele (C)...

The objective of this study was to evaluate the association between adherence to antipsychotic medication and working alliance (WA) ratings as reported separately by case manager (CM) and patient in first-episode psychosis (FEP) and to identify whether other factors previously related to adherence influence this relationship. Adherence was evaluate...

There is evidence of decreased pleasure and deficits in the anticipation of reward in both psychotic illness and drug addiction. Individuals with low anticipatory pleasure may preferentially engage in behaviours associated with immediate reward such as cannabis use. Ninety-one psychosis patients and 91 controls without history of psychosis were adm...

Adequate adherence to medication confers benefits on patients with psychotic illness, but is difficult to achieve. Efficacy of medication influences adherence in patients in advanced phases of illness and may have a similar influence on patients with a first episode of psychosis (FEP). We assessed medication adherence and efficacy in 216 FEP patien...

A history of childhood symptoms of inattention-hyperactivity is often reported in first episode psychosis (FEP) as is cannabis use. In the general population childhood ADHD predicts future cannabis use but the relationship has not been tested in FEP. Parents of patients with a first episode of psychosis (n=75) retrospectively assessed their affecte...

This study evaluates how much agreement there is between subjective reports of adherence to antipsychotic medication and objective or derived measures of adherence in first-episode psychosis (FEP) and asks if any adherence measure could approximate a gold standard based on correlation to symptom improvement in the early phase of treatment. Adherenc...

To determine the clinical relevance of different definitions of symptom remission for prediction of functional outcome in first-episode psychosis (FEP). One hundred forty-one individuals receiving treatment for an FEP at a specialized early intervention service had positive and negative symptoms and functional status rated every month over the firs...

Few studies have examined the underlying factor structure of signs and symptoms occurring before the first psychotic episode. Our objective was to determine whether factors derived from early signs and symptoms are differentially associated with non-affective versus affective psychosis. A principal components factor analysis was performed on early...

To assess whether an Early Case Identification Program (ECIP) for first-episode psychosis (FEP), which showed no significant short-term effects, has a delayed impact on duration of untreated psychosis (DUP). Using a historical control design, FEP patients were assessed on clinical variables over three consecutive phases, 2 years prior, 2 years duri...

To determine the validity and reliability of the Alcohol Use Disorders Identification Test (AUDIT) and Drug Abuse Screening Test (DAST) for detecting alcohol and drug use disorders, respectively, in a population with first-episode psychosis (FEP). Subjects with FEP completed the AUDIT and DAST and were divided into groups according to the presence...

Differential association of risk factors associated with relapse following treatment of first-episode psychosis (FEP) have not been studied adequately, especially for patients treated in specialized early intervention (SEI) services, where some of the usual risk factors may be ameliorated. Consecutive FEP patients treated in an SEI service over a 4...

Repeated administration of amphetamine in animals induces persistent changes in dopamine (DA) functions and behaviour. These changes may be mediated by altered plasticity of the mesocorticolimbic DA system. We have previously reported changes in the content of axonal plasma membrane protein syntaxin-1 in the nucleus accumbens (NAc) of amphetamine-s...

Although the etiology of neurodevelopmental mental disorders remains obscure, converging lines of evidence using animal modeling suggest a critical role for activity-dependent neurodevelopmental processes during neonatal life. Here, we report the behavioral effects of a novel technique designed to induce targeted, transient disruption of activity-d...

Between April 1992 and April 1994, 185 patients were waiting for a cardiac transplant at our institution. Transplantation was performed in 118 of these patients. Twenty-six patients (14%) died while awaiting a donor heart: 13 of these were in the intensive care unit on multiple inotropic medications, mechanical support, or both; another 13 were eit...

Cardiac transplantation improves survival and quality of life in patients with end-stage heart disease. Sexual function plays an integral role in quality of life, but little is known about the impact of cardiac transplantation on sexual behavior. The effects of cardiac transplantation on sexual function were evaluated in 41 patients pre- and posttr...

Due to the high incidence of death while awaiting cardiac transplantation today, most major transplant centers have adopted the use of left ventricular assist devices in order to stave off the complications of end-stage heart failure and allow patients to maintain a good physiologic state going into heart transplantation. These devices are safe and...

Congestive heart failure is a public health problem with an estimated 400,000 cases occurring each year in the United States. Despite medical therapy with digitalis, diuretics, and ACE inhibitors, many patients become refractory to treatment and might require parenteral inotropic therapy. In our experience, outpatient dobutamine can be administered...