Sidney H Kennedy

University of Toronto | U of T · Department of Psychiatry

Objective: The authors used a population-representative sample and health administrative data to quantify suicide-related behavior leading to acute care or deaths across self-identified heterosexual, gay/lesbian, and bisexual individuals. Methods: Data from a population-based survey (N=123,995) were linked to health administrative data (2002-201...

Importance: Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Identifying neuroimaging-based biomarkers might aid in defining the disease-related dimensions that characterize MDD and predict treatment response. Objective: To investigate the neuroanatomical dimensions that charact...

Background: Identifying early biomarkers of serious mental illness (SMI)—such as changes in brain structure and function—can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI. Methods: Participants were classified as healthy controls (HC; n=33), familial risk for seri...

The hypothalamus is a small grey matter structure which plays a crucial role in many physiological functions. Some studies have found an association between hypothalamic volume and psychopathology, which stresses the need for a standardized method to maximize segmentation accuracy. Here, we provide a detailed step-by-step method outlining the proce...

Background Prediction of treatment outcomes is a key step in improving the treatment of major depressive disorder (MDD). The Canadian Biomarker Integration Network in Depression (CAN-BIND) aims to predict antidepressant treatment outcomes through analyses of clinical assessment, neuroimaging, and blood biomarkers. Methods In the CAN-BIND-1 dataset...

Objectives Caring Contacts are an emerging intervention that aims to reduce distress and suicide risk after acute psychiatric care. This trial aimed to determine whether, during a pandemic, there was any evidence that the mental health benefits and reduction in suicidal ideation (SI) associated with delivering Caring Contacts to recently discharged...

Objective Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for...

Background Cognitive behavioral therapy (CBT) is an efficacious treatment for depression. CBT may in part exert its therapeutic effect by strengthening inhibitory control (IC). However, the relationship between CBT and IC has yet to be thoroughly explored; in particular, it is not clear whether IC is modulated following a course of CBT. Methods Fo...

Background Men who present to the emergency department (ED) with self-harm are at high risk of dying by suicide, with 2.7% of men dying in the year following their presentation, more than double the rate for women (1.2%). Despite this, care received after an ED visit is highly variable and many are not assessed for psychological needs. Furthermore,...

Introduction: An increasing number of studies are examining the link between the endocannabinoidome and major depressive disorder (MDD). We conducted an exploratory analysis of this system to identify potential markers of treatment outcomes. Methods: The dataset of the Canadian Biomarker Integration Network in Depression-1 study, consisting of 1...

Background: Although anhedonia is a key symptom of major depressive disorder (MDD), there is neither a concise nor effective method to distinguish and define anhedonia in MDD. The current study attempts to answer two questions based on validating the Dimensional Anhedonia Rating Scale (DARS) in Chinese MDD patients: 1) whether anhedonia subgroup c...

Many previous intervention studies have used functional magnetic resonance imaging (fMRI) data to predict the antidepressant response of patients with major depressive disorder (MDD); however, practical constraints have limited many of those attempts to small, single centre studies which may not adequately reflect how these models will generalize w...

Background Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders. Objective The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bip...

Background In treatment studies of major depressive disorder (MDD), exposure to major life events predicts less symptom improvement and greater likelihood of relapse. In contrast, the impact of minor life events has received less attention. We hypothesized that the impact of minor events on symptom improvement and risk of relapse would be heightene...

Background: Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction. Aims: Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association...

Objective: To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects. Methods: 188 of the 211 trial participants provided informa...

Background Although there is substantial research demonstrating the effects of duration and quality of sleep on outcomes in major depressive disorder (MDD), there is little research examining whether rhythmicity of sleep can also affect outcomes in MDD. The objective of our study was to investigate the relationship between rhythmicity of sleep and...

Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking...

(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (1H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, Psy...

This study was designed to explore the clinical belief that "set and setting" play an important role in favorable responses to psychedelic agents such as ketamine (KET). In fact, there is evidence in animals that the antidepressant effect of this drug may involve drug-environment interactions in which a context paired with its effects acquires the...

Escitalopram may have pain-alleviating effects for patients with comorbid pain and depression. This study aimed to quantify improvements in pain for patients on escitalopram and adjunctive aripiprazole. A secondary analysis of the CAN-BIND-1 trial was conducted which only included participants with a current depressive episode and pain. Participant...

Objective: To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N2 O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape. Methods: A comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLI...

To define treatment response in depression as at least a 50% reduction in total symptom severity is to accept that up to half of patients will continue to have residual symptoms, most commonly low mood/loss of interest, cognitive problems, lack of energy, and difficulty sleeping. In fact, patients' goals for treatment are to return to premorbid lev...

Psychiatric symptoms following concussion are prevalent and associated with a plethora of negative consequences including elevated post-concussive symptoms, cognitive disturbances, and poorer quality of life. With a primary focus on depression and post-traumatic stress disorder (PTSD), this chapter provides an overview of factors relating to the di...

Background Major depressive disorder (MDD) is a persistent psychiatric condition and one of the leading causes of global disease burden. In a previous study, we investigated the effects of a five-week intervention consisting of rhythmic gamma frequency (30-70 Hz) vibroacoustic stimulation in 20 patients formally diagnosed with MDD. In that study, t...

Some research suggests that distress, secondary to isolation and fear following COVID-19 infection, can negatively affect the long-term more than the COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors, ranging from the direct effect...

The Ontario Brain Institute's "Brain-CODE" is a large-scale informatics platform designed to support the collection, storage and integration of diverse types of data across several brain disorders as a means to understand underlying causes of brain dysfunction and developing novel approaches to treatment. By providing access to aggregated datasets...

The habenula (Hb) is a small, evolutionarily conserved epithalamic structure implicated in functions such as reward and mood regulation. Prior imaging work suggests that Hb's structural and functional properties may relate to treatment response in depression and other mood disorders. We used multimodal MRI techniques to investigate the potential in...

Youth at clinical high risk (CHR) for psychosis can present not only with characteristic attenuated psychotic symptoms but also may have other comorbid conditions, including anxiety and depression. These undifferentiated mood symptoms can overlap with the clinical presentation of youth with Distress syndromes. Increased resting-state functional con...

Background Major Depressive Disorder (MDD) is associated with various cognitive impairments, including response inhibition. Deficits in response inhibition may also underlie poor antidepressant treatment response. Recent studies revealed that the neurobiological correlates of response inhibition can predict response to pharmacological treatments. H...

Neuroimaging studies have demonstrated aberrant structure and function of the “cognitive-affective cerebellum” in major depressive disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks i...

Research suggests that distress secondary to the isolation and fear associated with COVID-19 infection can have more negative effects than the COVID-19 infection itself. This narrative review provides a global view of neuropsychiatric consequences. Several factors are responsible, ranging from the direct effects of infection, to the body’s response...

Some research suggested that distress secondary to isolation and fear can negatively affect the long-term than COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors ranging from the direct effect of infection to the body's responses aga...

Objectives The COVID-19 pandemic has contributed to a shift from in-person to remote mental health care. While remote care methods have long existed, their widespread use is unprecedented. There is little research about mental health care user and provider experiences with this transition, and no published studies to date have compared satisfaction...

Objective: To determine the objective neurocognitive effects of (1) single-dose ketamine, (2) repeated-dose ketamine, (3) ketamine adjunct to electroconvulsive therapy (ECT), and (4) ketamine as the anesthetic for ECT in major depressive disorder (MDD) and depression in bipolar disorder (BD). Data Sources: Cochrane, MEDLINE, Embase, and PsycINFO d...

Objective: To investigate the disparity in suicide-related behaviours across sexual orientations by gender. Design: Retrospective cohort study using a linkage of population-based survey and health administrative data. Setting: Ontario, Canada between January 2002 and December 2019 Participants: 123,995 residents aged 10+ were followed up for non...

Clinically oriented studies commonly acquire diffusion MRI (dMRI) data with a single non-zero b-value (i.e. single-shell) and diffusion weighting of b =1000 s/mm ² . To produce microstructural parameter maps, the tensor model is usually used, despite known limitations. Although compartment models have demonstrated improved fits in multi-shell dMRI...

Objective The Dimensional Anhedonia Rating Scale (DARS) is a novel questionnaire to assess anhedonia of recent validation. In this work we aim to study the equivalence between the traditional paper-and-pencil and the digital format of DARS. Methods 69 patients filled the DARS in a paper-based and digital versions. We assessed differences between f...

Deep brain stimulation targeting the subcallosal cingulate area, a hub with multiple axonal projections, has shown therapeutic potential for treatment-resistant mood disorders. While subcallosal cingulate deep brain stimulation drives long-term metabolic changes in corticolimbic circuits, the brain areas that are directly modulated by electrical st...

Stellate ganglion block (SGB) is a procedure involving the injection of a local anesthetic surrounding the stellate ganglion to inhibit sympathetic outflow. The objective of this review was to summarize existing evidence on the use of SGB in adults with psychiatric disorders. A systematic search identified 17 published studies and 4 registered clin...

Previous work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEV) to circumvent the...

Introduction : Although anxiety symptoms frequently co-occur with major depressive disorder, few studies examined the prediction of treatment outcomes among participants with anxious depression receiving antidepressants. We investigated whether baseline anxiety, and early improvements in anxiety and depression symptoms predict eventual treatment ou...

Despite the wide application of the magnetic resonance imaging (MRI) technique, there are no widely used standards on naming and describing MRI sequences. The absence of consistent naming conventions presents a major challenge in automating image processing since most MRI software require a priori knowledge of the type of the MRI sequences to be pr...

Background Growing evidence suggests cognitive deficits may represent neurocognitive markers with predictive utility in identifying those at risk for suicide. Characterizing these deficits may offer the opportunity to develop targeted interventions. Aim The aim of this systematic qualitative review is to provide a synthesis of the published data o...

Objectives Previous studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response. Methods Individuals in a major depressive epis...

Background Multiple treatments are effective for major depressive disorder (MDD), but the outcomes of each treatment vary broadly among individuals. Accurate prediction of outcomes is needed to help select a treatment that is likely to work for a given person. We aim to examine the performance of machine learning methods in delivering replicable pr...

Objectives The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendati...

Objectives: The COVID-19 pandemic has disrupted the provision of essential and potentially life-saving procedural treatments such as electroconvulsive therapy (ECT). We surveyed ECT providers across Canada to understand how the first wave of the pandemic affected ECT delivery between mid-March 2020 and mid-May 2020. Methods: The survey was admin...

The pathophysiology of major depressive disorder (MDD) encompasses an array of changes at molecular and neurobiological levels. As chronic stress promotes neurotoxicity there are alterations in the expression of genes and gene-regulatory molecules. The hippocampus is particularly sensitive to the effects of stress and its posterior volumes can deli...

Background Numerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions. Objective/hypothesis We sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field. Methods ClinicalTrials.gov (https://www.clini...

Background : Major Depressive Disorder (MDD) is characterized by objective and subjective cognitive deficits. Discrepancies between objective and subjective cognitive performance can reflect under- to over-estimations of cognitive abilities, and these discrepancies are referred to as cognitive self-appraisals. Despite evidence that low self-apprais...

Objective To evaluate whether accelerated brain aging occurs in individuals with mood or psychotic disorders. Methods A systematic review following PRISMA guidelines was conducted. A meta-analysis was then performed to assess neuroimaging-derived brain age gap in three independent groups: (1) schizophrenia and first-episode psychosis, (2) major de...

Background: Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD) that can increase treatment capacity. Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly. Objective: /Hypothesis- We compare...

Background: Measurement-based care (MBC) is an evidence-based practice that incorporates routine outcome assessment using validated rating scales to guide collaborative clinical decision-making. Although MBC results in improved outcomes for patients with major depressive disorder (MDD), there are barriers to its broad implementation in clinical set...

Identifying biomarkers of antidepressant response may advance personalized treatment of major depressive disorder (MDD). We aimed to identify longitudinal changes in gene expression associated with response to antidepressants in a sample of MDD patients treated with escitalopram. Patients ( N = 153) from the CAN-BIND-1 cohort were treated for 8 wee...

Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. So far, findings are variable and large sample replications scarce. We aimed to replicate and extend altered functional connectivity associated with MDD and pharmacotherapy outcomes in a large, multisite sample. Resting-stat...

Subcallosal cingulate deep brain stimulation produces long-term clinical improvement in approximately half of patients with severe treatment-resistant depression. We hypothesized that both structural and functional brain attributes may be important in determining responsiveness to this therapy. In a treatment-resistant depression subcallosal cingul...

There is a growing interest in examining the wealth of data generated by fusing functional and structural imaging information sources. These approaches may have clinical utility in identifying disruptions in the brain networks that underlie major depressive disorder (MDD). We combined an existing software toolbox with a mathematically dense statist...

One of the biggest challenges in treating depression is the heterogeneous and qualitative nature of its clinical presentations. This highlights the need to find quantitative molecular markers to tailor existing treatment strategies to the individual’s biological system. In this study, high-resolution metabolic phenotyping of urine and plasma sample...

Introduction Cognitive behavioural therapy (CBT) is an established first-line treatment for depression; however, it remains unclear which factors predict a positive outcome with this approach. Prior work suggests that co-morbid obesity predicts a poorer response to antidepressant medication. The current study examined whether there is an associatio...

Objective: Neuroimaging studies have demonstrated aberrant structure and function of the "cognitive-affective cerebellum" in Major Depressive Disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional...

Objectives Antidepressants are first-line treatments for major depressive disorder (MDD), but 40–60% of patients will not respond, hence, predicting response would be a major clinical advance. Machine learning algorithms hold promise to predict treatment outcomes based on clinical symptoms and episode features. We sought to independently replicate...