Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Oct 1, 2019
While response to antidepressants in major depressive disorder (MDD) is difficult to predict, cha... more While response to antidepressants in major depressive disorder (MDD) is difficult to predict, characterizing the organization and integrity of white matter in the brain with diffusion tensor imaging (DTI) may provide the means to distinguish between antidepressant Responders and Non-Responders. DTI data were collected at six sites (CAN-BIND-1 study) from 200 (127 female) depressed and 112 (71 female) healthy participants at three time-points: at baseline, 2 weeks and 8 weeks following initiation of an SSRI treatment. Therapeutic response was established by a 50% reduction of symptoms at 8 weeks. Analysis on Responders, Non-Responders and Controls yielded four scalar metrics: fractional anisotropy, and mean, axial, and radial diffusivity. Regionof-interest (ROI) analysis was carried out on 40 white matter regions using a skeletonization approach. Mixed effects regression was incorporated to test temporal trends. The data acquired at baseline showed that axial diffusivity in the external capsule, which overlaps the superior longitudinal fasciculus, was significantly associated with medication response. Regression analysis revealed further baseline differences of Responders from Non-Responders in the cingulum regions, sagittal stratum, and corona radiata. Additional group differences relative to Controls were seen in the internal capsule, posterior thalamic radiation, and uncinate fasciculus. Most effect sizes were moderate (near 0.5), with a maximum of 0.76 in the cingulum-hippocampus region. No temporal changes in DTI metrics were observed over the 8-week study period. Several DTI measures of altered white matter specifically distinguished medication Responders and Non-Responders at baseline, and show promise for predicting treatment response in depression.
Background: Individuals with depression exhibit attenuated reactivity to both positive and negati... more Background: Individuals with depression exhibit attenuated reactivity to both positive and negative emotional stimuli. This study examined differences in behavioural performance and in blood-oxygen level dependent (BOLD) neural activation patterns between unmedicated individuals with major depressive disorder (MDD) and healthy comparison participants (HC) on an emotional conflict task. We studied 48 MDD and 30 HC who performed an emotional conflict task in a functional magnetic resonance imaging (fMRI) scanner. Results: On the emotional conflict task, MDD and HC demonstrated a robust emotional Stroop effect in reaction time and accuracy. Overall accuracy was lower in MDD compared to HC with no significant reaction time differences. The fMRI data indicated lower BOLD activation in MDD compared to HC on comparisons of all trials, congruent, incongruent, and incongruent > congruent trials in regions including right inferior temporal gyrus, lateral occipital cortex, and occipital fusiform gyrus. Behavioural and neuroimaging data indicated no group differences in fearful versus happy face processing.
Objectives The COVID-19 pandemic has contributed to a shift from in-person to remote mental healt... more 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 between these groups. Methods Canadian mental health care users ( n = 332) and providers ( n = 107) completed an online self-report survey from October 2020 to February 2021 hosted by the Canadian Biomarker Integration Network in Depression. Using a mixed-methods approach, participants were asked about their use of remote care, including satisfaction, barriers to use, helpful and unhelpful factors, and suggestions for improvement. Results Overall, 59% to 63% of health care users and 59% of health care providers were satisfied with remote care. Users reported the greatest satisfaction with the convenience of remote care, while providers were most satisfied with the speed of provision of care; all groups were least satisfied with therapeutic rapport. Health care providers were less satisfied with the user-friendliness of remote care ( P < 0.001) than users, while health care users were less satisfied than providers with continuity of care ( P < 0.001). The use of a video-based platform was associated with remote care satisfaction among health care users ( P < 0.02), and qualitative responses support the importance of visual cues in maintaining therapeutic rapport remotely. The majority of users (55%) and providers (87%) reported a likelihood of using remote care after the pandemic. Conclusions Remote mental health care is generally accepted by both users and providers, and the majority would consider using remote care following the pandemic. Suggestions for improvement include greater use of video, increased attention to body language and eye contact, consistency with in-person care, as well as increased provider training and administrative support.
Objective: To determine the objective neurocognitive effects of (1) single-dose ketamine, (2) rep... more 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 databases were searched on March 19, 2020 (updated July 2, 2020), using the terms terms major depressive disorder bipolar disorder and ketamine and their synonyms. Clinical trial registries (search date May 4, 2020) and reference sections of included articles were also searched. There was no restriction on language or year of publication. Study Selection: Of 4,035 identified articles, 17 met inclusion criteria. Controlled and open-label studies of adults who received at least 1 ketamine treatment for a current major depressive episode, as part of MDD or BD, were included. Only studies measuring cognition using at least 1 validated, objective neurocognitive assessment were eligible. Data Extraction: Results are presented using a narrative review format. Data regarding change in cognitive performance from baseline to end-of-treatment and/or differences in cognition between ketamine and control groups were extracted. Results: There were no negative effects of single- or repeated-dose intravenous ketamine up to 2 weeks post-treatment in MDD. Limited data were available for BD populations, as well as on other routes of ketamine administration. Conclusions: Data to definitively answer the question of whether ketamine has substantive or persistent cognitive effects are insufficient; thus, larger controlled trials measuring cognition as the primary outcome are needed. Future research should focus on different routes of ketamine administration, ketamine enantiomers, and BD populations.
Testing a deep convolutional neural network for automated hippocampus segmentation in a longitudi... more Testing a deep convolutional neural network for automated hippocampus segmentation in a longitudinal sample of healthy participants, NeuroImage (2019),
Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refr... more Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics. Methods: This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score $18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics. Results: Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory. Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.
Conclusions : Reward sensitivity was related to recurrence of mania over time, while the type of ... more Conclusions : Reward sensitivity was related to recurrence of mania over time, while the type of BD predicted time to recurrence of depression. The main result partially confirms prior studies about the link between BAS and mania, but the power and the fact that this sample was specifically seeking psychosocial treatment might have attenuated the effect. CATEGORY : Psychological treatments
Highlights • Depression was associated with a larger brain-age gap in older individuals.• Body ma... more Highlights • Depression was associated with a larger brain-age gap in older individuals.• Body mass index was associated with a larger brain-age gap.• Brain-age gap was not associated with an overall antidepressant treatment response.
Introduction: Primary motor abnormalities are common among patients with schizophrenia. Studies u... more Introduction: Primary motor abnormalities are common among patients with schizophrenia. Studies using non-invasive brain stimulation have suggested that motor impairment is a trait marker of schizophrenia linked to impairment in GABA-mediated cortical inhibition. This study sheds light on the nature and temporal course of cortical inhibition deficits in schizophrenia by studying patients in two different phases of the disease (acute and subacute/residual) using a longitudinal design. Methods: Twenty-eight patients were evaluated using a single and pairedpulse transcranial stimulation protocol, which assessed cortical inhibition, during acute psychosis. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A followup assessment was performed in the 28 patients three months later, when there was remission from their psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. Results: As previously described, patients showed reduced short and longintracortical inhibition (SICI and LICI), reduced interhemispheric inhibition (IHI) and reduced cortical silent period (CSP). In the follow-up assessment, 18 patients were in remission and 10 showed residual symptomatology. A second TMS study revealed that deficits persisted in SICI and IHI whereas CSP and LICI measures did not differed from those of healthy subjects. A multivariate regression analysis found that LICI and CSP measures were mainly associated to anti-psychotic medication and presence of positive symptoms at both assessments. Discussion: Our data support the hypothesis that cortical inhibition deficits are both trait and state markers of the disease, depending of the type GABAergic system involved. Whereas GABAB-mediated inhibition deficits are linked to variables associated to the state of the disease (treatment, severity of symptoms), deficits associated to GABA A appear to be more stable across different phases of the disease.
Progress in Neuro-psychopharmacology & Biological Psychiatry, Dec 1, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Exposure to stressful life events and individual differences in the personality trait neuroticism... more Exposure to stressful life events and individual differences in the personality trait neuroticism are important risk factors that interact to predict major depressive disorder (MDD). Less is known about their effect on treatment response in depression. Here, we examine whether stressful life events experienced prior to and during treatment interact with neuroticism to predict response to 16‐week pharmacotherapy for MDD. Participants included 159 outpatients with MDD who were initially treated with 8 weeks of escitalopram. Those who responded to the initial treatment continued on escitalopram monotherapy, whereas non‐responders received 8 weeks of adjunctive aripiprazole. Personality was assessed using the NEO‐Five Factor Inventory, and stressful life events were assessed using the Life Events and Difficulties Schedule, a rigorous contextual interview that includes independent ratings of threatening life events. High baseline neuroticism was associated with a lower likelihood of resp...
Objective. There is limited literature on associations between inflammatory tone and response to ... more Objective. There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). Methods. In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10-20 mg daily for 8 weeks. Responders continued escitalopram while nonresponders received adjunctive aripiprazole 2-10 mg daily for 8 weeks. Plasma levels of proinflammatory markers-C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C-C motif ligand-2 (CCL-2)measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response. Results. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16. Conclusion. Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with nonresponse to adjunctive aripiprazole. These findings require validation in independent clinical populations.
The Ontario Brain Institute's “Brain-CODE” is a large-scale informatics platform designed to ... more 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 on participants with and without different brain disorders, Brain-CODE will facilitate analyses both within and across diseases and cover multiple brain disorders and a wide array of data, including clinical, neuroimaging, and molecular. To help achieve these goals, consensus methodology was used to identify a set of core demographic and clinical variables that should be routinely collected across all participating programs. Establishment of Common Data Elements within Brain-CODE is critical to enable a high degree of consistency in data collection across studies and thus optimize the ability of investigators to analyze pooled particip...
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Oct 1, 2019
While response to antidepressants in major depressive disorder (MDD) is difficult to predict, cha... more While response to antidepressants in major depressive disorder (MDD) is difficult to predict, characterizing the organization and integrity of white matter in the brain with diffusion tensor imaging (DTI) may provide the means to distinguish between antidepressant Responders and Non-Responders. DTI data were collected at six sites (CAN-BIND-1 study) from 200 (127 female) depressed and 112 (71 female) healthy participants at three time-points: at baseline, 2 weeks and 8 weeks following initiation of an SSRI treatment. Therapeutic response was established by a 50% reduction of symptoms at 8 weeks. Analysis on Responders, Non-Responders and Controls yielded four scalar metrics: fractional anisotropy, and mean, axial, and radial diffusivity. Regionof-interest (ROI) analysis was carried out on 40 white matter regions using a skeletonization approach. Mixed effects regression was incorporated to test temporal trends. The data acquired at baseline showed that axial diffusivity in the external capsule, which overlaps the superior longitudinal fasciculus, was significantly associated with medication response. Regression analysis revealed further baseline differences of Responders from Non-Responders in the cingulum regions, sagittal stratum, and corona radiata. Additional group differences relative to Controls were seen in the internal capsule, posterior thalamic radiation, and uncinate fasciculus. Most effect sizes were moderate (near 0.5), with a maximum of 0.76 in the cingulum-hippocampus region. No temporal changes in DTI metrics were observed over the 8-week study period. Several DTI measures of altered white matter specifically distinguished medication Responders and Non-Responders at baseline, and show promise for predicting treatment response in depression.
Background: Individuals with depression exhibit attenuated reactivity to both positive and negati... more Background: Individuals with depression exhibit attenuated reactivity to both positive and negative emotional stimuli. This study examined differences in behavioural performance and in blood-oxygen level dependent (BOLD) neural activation patterns between unmedicated individuals with major depressive disorder (MDD) and healthy comparison participants (HC) on an emotional conflict task. We studied 48 MDD and 30 HC who performed an emotional conflict task in a functional magnetic resonance imaging (fMRI) scanner. Results: On the emotional conflict task, MDD and HC demonstrated a robust emotional Stroop effect in reaction time and accuracy. Overall accuracy was lower in MDD compared to HC with no significant reaction time differences. The fMRI data indicated lower BOLD activation in MDD compared to HC on comparisons of all trials, congruent, incongruent, and incongruent > congruent trials in regions including right inferior temporal gyrus, lateral occipital cortex, and occipital fusiform gyrus. Behavioural and neuroimaging data indicated no group differences in fearful versus happy face processing.
Objectives The COVID-19 pandemic has contributed to a shift from in-person to remote mental healt... more 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 between these groups. Methods Canadian mental health care users ( n = 332) and providers ( n = 107) completed an online self-report survey from October 2020 to February 2021 hosted by the Canadian Biomarker Integration Network in Depression. Using a mixed-methods approach, participants were asked about their use of remote care, including satisfaction, barriers to use, helpful and unhelpful factors, and suggestions for improvement. Results Overall, 59% to 63% of health care users and 59% of health care providers were satisfied with remote care. Users reported the greatest satisfaction with the convenience of remote care, while providers were most satisfied with the speed of provision of care; all groups were least satisfied with therapeutic rapport. Health care providers were less satisfied with the user-friendliness of remote care ( P < 0.001) than users, while health care users were less satisfied than providers with continuity of care ( P < 0.001). The use of a video-based platform was associated with remote care satisfaction among health care users ( P < 0.02), and qualitative responses support the importance of visual cues in maintaining therapeutic rapport remotely. The majority of users (55%) and providers (87%) reported a likelihood of using remote care after the pandemic. Conclusions Remote mental health care is generally accepted by both users and providers, and the majority would consider using remote care following the pandemic. Suggestions for improvement include greater use of video, increased attention to body language and eye contact, consistency with in-person care, as well as increased provider training and administrative support.
Objective: To determine the objective neurocognitive effects of (1) single-dose ketamine, (2) rep... more 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 databases were searched on March 19, 2020 (updated July 2, 2020), using the terms terms major depressive disorder bipolar disorder and ketamine and their synonyms. Clinical trial registries (search date May 4, 2020) and reference sections of included articles were also searched. There was no restriction on language or year of publication. Study Selection: Of 4,035 identified articles, 17 met inclusion criteria. Controlled and open-label studies of adults who received at least 1 ketamine treatment for a current major depressive episode, as part of MDD or BD, were included. Only studies measuring cognition using at least 1 validated, objective neurocognitive assessment were eligible. Data Extraction: Results are presented using a narrative review format. Data regarding change in cognitive performance from baseline to end-of-treatment and/or differences in cognition between ketamine and control groups were extracted. Results: There were no negative effects of single- or repeated-dose intravenous ketamine up to 2 weeks post-treatment in MDD. Limited data were available for BD populations, as well as on other routes of ketamine administration. Conclusions: Data to definitively answer the question of whether ketamine has substantive or persistent cognitive effects are insufficient; thus, larger controlled trials measuring cognition as the primary outcome are needed. Future research should focus on different routes of ketamine administration, ketamine enantiomers, and BD populations.
Testing a deep convolutional neural network for automated hippocampus segmentation in a longitudi... more Testing a deep convolutional neural network for automated hippocampus segmentation in a longitudinal sample of healthy participants, NeuroImage (2019),
Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refr... more Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics. Methods: This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score $18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics. Results: Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory. Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.
Conclusions : Reward sensitivity was related to recurrence of mania over time, while the type of ... more Conclusions : Reward sensitivity was related to recurrence of mania over time, while the type of BD predicted time to recurrence of depression. The main result partially confirms prior studies about the link between BAS and mania, but the power and the fact that this sample was specifically seeking psychosocial treatment might have attenuated the effect. CATEGORY : Psychological treatments
Highlights • Depression was associated with a larger brain-age gap in older individuals.• Body ma... more Highlights • Depression was associated with a larger brain-age gap in older individuals.• Body mass index was associated with a larger brain-age gap.• Brain-age gap was not associated with an overall antidepressant treatment response.
Introduction: Primary motor abnormalities are common among patients with schizophrenia. Studies u... more Introduction: Primary motor abnormalities are common among patients with schizophrenia. Studies using non-invasive brain stimulation have suggested that motor impairment is a trait marker of schizophrenia linked to impairment in GABA-mediated cortical inhibition. This study sheds light on the nature and temporal course of cortical inhibition deficits in schizophrenia by studying patients in two different phases of the disease (acute and subacute/residual) using a longitudinal design. Methods: Twenty-eight patients were evaluated using a single and pairedpulse transcranial stimulation protocol, which assessed cortical inhibition, during acute psychosis. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A followup assessment was performed in the 28 patients three months later, when there was remission from their psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. Results: As previously described, patients showed reduced short and longintracortical inhibition (SICI and LICI), reduced interhemispheric inhibition (IHI) and reduced cortical silent period (CSP). In the follow-up assessment, 18 patients were in remission and 10 showed residual symptomatology. A second TMS study revealed that deficits persisted in SICI and IHI whereas CSP and LICI measures did not differed from those of healthy subjects. A multivariate regression analysis found that LICI and CSP measures were mainly associated to anti-psychotic medication and presence of positive symptoms at both assessments. Discussion: Our data support the hypothesis that cortical inhibition deficits are both trait and state markers of the disease, depending of the type GABAergic system involved. Whereas GABAB-mediated inhibition deficits are linked to variables associated to the state of the disease (treatment, severity of symptoms), deficits associated to GABA A appear to be more stable across different phases of the disease.
Progress in Neuro-psychopharmacology & Biological Psychiatry, Dec 1, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Exposure to stressful life events and individual differences in the personality trait neuroticism... more Exposure to stressful life events and individual differences in the personality trait neuroticism are important risk factors that interact to predict major depressive disorder (MDD). Less is known about their effect on treatment response in depression. Here, we examine whether stressful life events experienced prior to and during treatment interact with neuroticism to predict response to 16‐week pharmacotherapy for MDD. Participants included 159 outpatients with MDD who were initially treated with 8 weeks of escitalopram. Those who responded to the initial treatment continued on escitalopram monotherapy, whereas non‐responders received 8 weeks of adjunctive aripiprazole. Personality was assessed using the NEO‐Five Factor Inventory, and stressful life events were assessed using the Life Events and Difficulties Schedule, a rigorous contextual interview that includes independent ratings of threatening life events. High baseline neuroticism was associated with a lower likelihood of resp...
Objective. There is limited literature on associations between inflammatory tone and response to ... more Objective. There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). Methods. In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10-20 mg daily for 8 weeks. Responders continued escitalopram while nonresponders received adjunctive aripiprazole 2-10 mg daily for 8 weeks. Plasma levels of proinflammatory markers-C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C-C motif ligand-2 (CCL-2)measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response. Results. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16. Conclusion. Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with nonresponse to adjunctive aripiprazole. These findings require validation in independent clinical populations.
The Ontario Brain Institute's “Brain-CODE” is a large-scale informatics platform designed to ... more 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 on participants with and without different brain disorders, Brain-CODE will facilitate analyses both within and across diseases and cover multiple brain disorders and a wide array of data, including clinical, neuroimaging, and molecular. To help achieve these goals, consensus methodology was used to identify a set of core demographic and clinical variables that should be routinely collected across all participating programs. Establishment of Common Data Elements within Brain-CODE is critical to enable a high degree of consistency in data collection across studies and thus optimize the ability of investigators to analyze pooled particip...
Background: Non-response to first-line treatment for major depressive disorder (MDD) is common; f... more Background: Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment. Objective: The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy. Methods: We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement. Results: Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain. Conclusion: The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms.
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Papers by Sidney Kennedy
Objective: The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy.
Methods: We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement.
Results: Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain.
Conclusion: The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms.