Publications by authors named "Roger S McIntyre"

675 Publications

Economic and Humanistic Burden Associated with Depression and Anxiety Among Adults with Non-Communicable Chronic Diseases (NCCDs) in the United States.

J Multidiscip Healthc 2021 23;14:887-896. Epub 2021 Apr 23.

Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada.

Introduction: Patients with both major depressive disorder (MDD) and generalized anxiety disorder (GAD) in addition to one or multiple comorbid non-communicable chronic diseases (NCCDs) face unique challenges. However, few studies have characterized how the burden of co-occurring MDD and GAD differs from that of only MDD or only GAD among patients with NCCDs.

Methods: In this study, we used Medical Expenditures Panel Survey data from 2010-2017 to understand how the economic and humanistic burden of co-occurring MDD and GAD differs from that of MDD or GAD alone among patients with NCCDs. We used generalized linear models to investigate this relationship and controlled for patient sociodemographics and clinical characteristics.

Results: Co-occurring MDD and GAD was associated with increases in mean annual per patient inpatient visits, office visits, emergency department visits, annual drug costs, and total medical costs. Among patients with 3+ NCCDs, MDD or GAD only was associated with lower odds ratios (ORs) of limitations in activities of daily living (ADLs; 0.532 and 0.508, respectively) and social (0.503, 0.526) and physical limitations (0.613, 0.613) compared to co-occurring MDD and GAD. Compared to patients with co-occurring MDD and GAD, having MDD only or GAD only was associated with significantly lower odds of cognitive limitations (0.659 and 0.461, respectively) in patients with 1-2 NCCDs and patients with 3+ NCCDs (0.511, 0.416).

Discussion: Comorbid MDD and GAD was associated with higher economic burden, lower quality of life, and greater limitations in daily living compared to MDD or GAD alone. Health-related economic and humanistic burden increased with number of NCCDs.
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http://dx.doi.org/10.2147/JMDH.S280200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079356PMC
April 2021

Strategies to Prolong Ketamine's Efficacy in Adults with Treatment-Resistant Depression.

Adv Ther 2021 Apr 30. Epub 2021 Apr 30.

Mood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.

Introduction: Ketamine treatment is capable of significant and rapid symptom improvement in adults with treatment-resistant depression (TRD). A limitation of ketamine treatment in TRD is the relatively short duration of time to relapse (e.g., median 2-4 weeks). The objective of the systematic review herein is to identify strategies capable of prolonging the acute efficacy of ketamine in adults with TRD.

Methods: PubMed/MEDLINE databases were searched from inception to December 2020 for clinical studies written in English using the following key terms: ketamine, prolong, and depression. A total of 454 articles were identified from the literature search which included all clinical studies regarding prolonging the antidepressant effects of ketamine. Twenty-two articles were included: ten randomized controlled trials (RCTs), eight prospective open-label trials, one retrospective chart review, and three case reports. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data extraction. The primary outcome was prolonged effect, defined as statistically significant antidepressant effects following acute ketamine treatment.

Results: A total of 454 articles were identified, and 22 articles were included. Different treatment modalites including pharmacological interventions, manualized-based psychotherapies, electroconvulsive therapy, transcranial magnetic stimulation, and intravenous monotherapy were examined to determine their impact on the prolongation of antidepressant effects following acute ketamine treatment. No treatment modality, other than repeat-dose IV ketamine, has demonstrated ability to significantly prolong the acute efficacy of IV ketamine in TRD.

Conclusion: Hitherto, available open-label data and controlled trial data support repeat administration of IV ketamine as an effective strategy to prolong the efficacy of ketamine's antidepressant effects (although not the focus of the study herein, maintenance repeat-dose esketamine treatment is proven effective in esketamine responders). There is a need to identify multimodality strategies that are safe and capable of prolonging the efficacy of ketamine in adults with TRD.
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http://dx.doi.org/10.1007/s12325-021-01732-8DOI Listing
April 2021

Barriers, benefits and interventions for improving the delivery of telemental health services during the coronavirus disease 2019 pandemic: a systematic review.

Curr Opin Psychiatry 2021 Apr 28. Epub 2021 Apr 28.

Mood Disorders Psychopharmacology Unit, University Health Network Department of Pharmacology and Toxicology Department of Psychiatry, University of Toronto Brain and Cognition Discovery Foundation Poul Hansen Family Centre for Depression Toronto Western Hospital, University Health Network Canadian Rapid Treatment Centre of Excellence, Toronto, Ontario, Canada.

Purpose Of Review: To reduce the spread of infection from the coronavirus disease 2019 (COVID-19), mental healthcare facilities were forced to make the rapid transition from face-to-face services to virtual care. This systematic review aims to synthesize the extant literature reporting on barriers of telemental health (TMH) during the COVID-19 pandemic and how facilities have worked to overcome these barriers, to inform best practices for TMH delivery.

Recent Findings: Most recent findings came from case studies from mental health professionals which reported on barriers related to institutional, provider and patient factors, and how these barriers were overcome. Common barriers identified in the literature include: technological difficulties; issues regarding safety, privacy and confidentiality; therapeutic delivery and the patient-provider relationship; and a loss of sense of community. Studies also reported on the benefits to TMH interventions/tools, as well as suggestions for improvements in the delivery of TMH services.

Summary: As the COVID-19 pandemic evolves, mental healthcare providers continue to find creative and feasible solutions to overcome barriers to the delivery of TMH. Dissemination of these solutions is imperative to ensure the best quality of mental healthcare for patients across the globe.
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http://dx.doi.org/10.1097/YCO.0000000000000714DOI Listing
April 2021

Healthcare Provider Perspectives on Bipolar I Disorder Screening and the Rapid Mood Screener (RMS), a Pragmatic, New Tool.

CNS Spectr 2021 Apr;26(2):181-183

University of Barcelona, Barcelona, Spain.

Introduction: Although mania is the hallmark symptom of bipolar I disorder (BD-I), most patients initially present for treatment with depressive symptoms. Misdiagnosis of BD-I as major depressive disorder (MDD) is common, potentially resulting in poor outcomes and inappropriate antidepressant monotherapy treatment. Screening patients with depressive symptoms is a practical strategy to help healthcare providers (HCPs) identify when additional assessment for BD-I is warranted. The new 6-item Rapid Mood Screener (RMS) is a pragmatic patient-reported BD-I screening tool that relies on easily understood terminology to screen for manic symptoms and other BD-I features in <2 minutes. The RMS was validated in an observational study in patients with clinically confirmed BD-I (n=67) or MDD (n=72). When 4 or more items were endorsed ("yes"), the sensitivity of the RMS for identifying patients with BP-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. To more thoroughly understand screening tool use among HCPs, a 10-minute survey was conducted.

Methods: A nationwide sample of HCPs (N=200) was selected using multiple HCP panels; HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the widely recognized Mood Disorder Questionnaire (MDQ). Results were reported by grouped specialties (primary care physicians, general nurse practitioners [NPs]/physician assistants [PAs], psychiatrists, and psychiatric NPs/PAs). Included HCPs were in practice <30 years, spent at least 75% of their time in clinical practice, saw at least 10 patients with depression per month, and diagnosed MDD or BD in at least 1 patient per month. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence interval.

Results: Among HCPs, 82% used a tool to screen for MDD, while 32% used a tool for BD. Screening tool attributes considered to be of the greatest value included sensitivity (68%), easy to answer questions (66%), specificity (65%), confidence in results (64%), and practicality (62%). Of HCPs familiar with screening tools, 70% thought the RMS was at least somewhat better than other screening tools. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. Most HCPs (81%) preferred the RMS to the MDQ, and the RMS significantly outperformed the MDQ across valued attributes; 76% reported that they were likely to use the RMS to screen new patients with depressive symptoms. A total of 84% said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.

Discussion: The RMS was viewed positively by HCPs who participated in a brief survey. A large percentage of respondents preferred the RMS over the MDQ and indicated that they would use it in their practice. Collectively, responses indicated that the RMS is likely to have a positive impact on screening behavior.

Funding: AbbVie Inc.
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http://dx.doi.org/10.1017/S1092852921000201DOI Listing
April 2021

Genetic association between major depressive disorder and type 2 diabetes mellitus: Shared pathways and protein networks.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Apr 26:110339. Epub 2021 Apr 26.

School of Psychology and Key Laboratory of Cognition and Personality (Ministry of Education), Southwest University, Chongqing 400715, PR China; National Demonstration Center for Experimental Psychology Education (Southwest University), , Chongqing 400715, PR China. Electronic address:

Background: Major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) are common public health disorders that often co-occur. This study aims to determine whether gene expression profiles from individuals with MDD or T2DM overlap and if there are any functional interconnectivity between identified genes using protein-protein interaction (PPI).

Methods: The DNA microarray datasets were extracted from the Gene Expression Omnibus. Gene expression dataset GSE98793 from a case-control study of MDD (64 healthy control subjects, 128 patients) and dataset GSE15653 from a case-control study of T2DM (nine controls, nine individuals with T2DM) were used for this secondary and post-hoc analysis. GO enrichment analyses and Reactome pathway enrichment analysis were performed for functional enrichment analyses with the shared genes. PPI networks, PPI clusters and hub genes were performed to detect the potential relationships among differentially expressed genes (DEG) -encoding proteins in both MDD and T2DM.

Results: A total of 3640 DEGs were identified in the MDD group when compared to the control group, whereas 3700 DEGs were identified in the T2DM group when compared to the control groups, among which 244 DEGs were overlap genes. The identified DEGs were enriched for Interleukin-4 and Interleukin-13 signaling, neutrophil degranulation, as well as other select species of the innate immune system. The biological processes of neurofibrillary tangle assembly regulation, tau-protein kinase activity regulation, amyloid-beta clearance regulation, amyloid-beta formation regulation and neuron apoptotic processes were also identified. Molecular function analysis indicated that identified genes were mainly enriched for amyloid-beta binding. 925 out of 1006 protein-protein interactions and six sub-networks were identified reflecting the disparate biological domains of overlapping genes. Ten hub genes further highlight the putative importance of tau-protein kinase activity, inflammatory response and neuron apoptotic regulatory processes across MDD and T2DM.

Conclusions: Our results indicate that an overlapping genetic architecture subserves MDD and T2DM. Genes relevant to the innate immune system, tau protein formation, and cellular aging were identified. Results indicate that the common, often comorbid, conditions of MDD and T2DM have a pathoetiologic nexus.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110339DOI Listing
April 2021

The associations between sleep situations and mental health among Chinese adolescents: A longitudinal study.

Sleep Med 2021 Mar 13;82:71-77. Epub 2021 Mar 13.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.

Objective: Few studies are conducted to explore the longitudinal relationships between sleep situations and mental health among adolecents. This study aimed to explore the sleep situations (ie, sleep habits and sleep problems) among Chinese adolescents and the longitudinal associations between sleep situations and mental disorder symptoms (ie, depressive and anxiety symptoms).

Methods: This longitudinal study included 1957 high school students from ten schools in Guangzhou in January 2019, with 1836 students contributing valid data at a one-year follow-up (retention rate: 93.9%). Data of depressive and anxiety symptoms, sleep habits, and sleep problems were collected using a self-reported questionnaire.

Results: The current study found that over half of the adolescents did not reach the recommended 8-h sleep-time on weekdays (63.3%). Short sleep duration, especially on weekdays, was significantly associated with subsequent depressive (AOR = 0.86, 95%CI: 0.80-0.92) and anxiety symptoms (AOR = 0.86, 95%CI: 0.77-0.96). In addition, longer weekday-weekend catch-up sleep and more sleep problems were risk factors of depressive and anxiety symptoms.

Conclusions: The health effects of insufficient sleep and suboptimal sleep quality on adolescents should not be neglected. Our longitudinal research showed that adolescents would demonstrate severer depressive and anxiety symptoms if lacking of a healthy sleeping practice. A regular sleep schedule and close attention to adolescents' mental disorders are highly recommended.
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http://dx.doi.org/10.1016/j.sleep.2021.03.009DOI Listing
March 2021

The relationship between childhood emotional abuse and depressive symptoms among Chinese college students: The multiple mediating effects of emotional and behavioral problems.

J Affect Disord 2021 Mar 31;288:129-135. Epub 2021 Mar 31.

Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Background: This study aims to explore the mediational effects of emotional and behavioral problems on the association between childhood emotional abuse and depressive symptoms among college students.

Methods: Data were drawn from 60 universities from 10 provinces in China (n=30,374). Information about childhood maltreatment, depressive symptoms, emotional and behavioral problems were gathered through the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Center for Epidemiologic Studies Depression Scale (CES-D) and the Strengths and Difficulties Questionnaire (SDQ), respectively. Univariable and multivariable logistic regression models and mediating models were used.

Results: After controlling for demographic factors, childhood emotional abuse was the strongest risk factor for depressive symptoms (adjusted odds ratio (aOR)=2.54, 95%CI=2.27-2.85). The relationship between childhood emotional abuse and depressive symptoms was partially mediated by emotional and behavioral problems with 68.7% total indirect effect. Among the 5 identified subtypes of emotional and behavioral problems, the mediating effects of emotional problems (57.3%) and hyperactivity (28.6%) were higher than peer problems (7.8%) and prosocial behavior (3.6%). Conduct problems did not show a significant mediating effect (p>0.05).

Limitations: The cross-sectional design is limited to make inferences about causality.

Conclusions: Childhood emotional abuse was strongly associated with depressive symptoms in college students. Of the five identified subtypes of emotional and behavioral problems, four subtypes mediated the relationship between childhood emotional abuse and depressive symptoms, including emotional problems, hyperactivity, peer problems and prosocial behavior.
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http://dx.doi.org/10.1016/j.jad.2021.03.074DOI Listing
March 2021

The impact of COVID-19 pandemic on global mental health: From the general public to healthcare workers.

Ann Acad Med Singap 2021 03;50(3):198-199

Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

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March 2021

The impact of COVID-19 pandemic on global mental health: From the general public to healthcare workers.

Ann Acad Med Singap 2021 03;50(3):198-199

Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

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March 2021

The impact of COVID-19 pandemic on global mental health: From the general public to healthcare workers.

Ann Acad Med Singap 2021 03;50(3):198-199

Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

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March 2021

The impact of overweight/obesity on monetary reward processing: A systematic review.

J Psychiatr Res 2021 May 18;137:456-464. Epub 2021 Mar 18.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

Objective: Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation).

Methods: PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese).

Results: Findings were reviewed from 11 studies evaluating the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity.

Conclusions: Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression.

Limitations: There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.029DOI Listing
May 2021

The impact of overweight/obesity on monetary reward processing: A systematic review.

J Psychiatr Res 2021 May 18;137:456-464. Epub 2021 Mar 18.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

Objective: Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation).

Methods: PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese).

Results: Findings were reviewed from 11 studies evaluating the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity.

Conclusions: Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression.

Limitations: There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.029DOI Listing
May 2021

Is Obesity A Determinant Of Success With Pharmacological Treatment For Depression? A Systematic Review, Meta-Analysis And Meta-Regression.

J Affect Disord 2021 May 15;287:54-68. Epub 2021 Mar 15.

Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network, Toronto, ON, Canada.

Background: The bidirectional association between Major Depressive Disorder (MDD) and obesity suggests that body mass index (BMI) at the baseline could influence remission rates (RR) with pharmacological treatment. We evaluated the influence of baseline BMI on the chances of remission among patients with MDD administered antidepressants.

Methods: Based on the guidelines of the PRISMA statement, we conducted a systematic review on PubMed, Cochrane and Embase databases with subsequent meta-analysis and meta-regression. We included only randomized controlled trials evaluating the efficacy of antidepressants of different classes (monotherapy and combined therapies) that evidenced baseline BMI assessment. We created a model to describe the linear relationship between baseline BMI and RR.

Results: Our systematic review yielded 70 studies with a total of 9,779 patients in the active group and 7,136 patients in the placebo group. In placebo controlled studies, BMI influenced the RR of patients randomized to active treatment. The RR for antidepressants in monotherapy was higher in normal weight to overweight patients rather than obese patients (33% vs 12%, respectively). Also in monotherapy, the RR is higher when the study is conducted on patients with a lower baseline BMI (p=0.029). For combined therapies, the pooled RR was higher in obese patients rather than in normal weight to overweight patients (75% vs 17%, respectively).

Limitations: BMI provides no information about body composition and obesity can be related to several potential confounders that potentially influence RR.

Conclusion: The RR with antidepressant therapy seems to be associated with baseline BMI in patients with MDD, although this simple variable was insufficiently explored so far.
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http://dx.doi.org/10.1016/j.jad.2021.03.032DOI Listing
May 2021

A chain mediation model on COVID-19 symptoms and mental health outcomes in Americans, Asians and Europeans.

Sci Rep 2021 03 19;11(1):6481. Epub 2021 Mar 19.

Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.
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http://dx.doi.org/10.1038/s41598-021-85943-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979938PMC
March 2021

Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation.

Am J Psychiatry 2021 Mar 17:appiajp202020081251. Epub 2021 Mar 17.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto (McIntyre, Rosenblat, Y. Lee, Lui, Mansur); Department of Psychiatry, University of Toronto, Toronto (McIntyre, Rosenblat, Mansur); Department of Pharmacology, University of Toronto, Toronto (McIntyre); Brain and Cognition Discovery Foundation, Toronto (McIntyre, Subramaniapillai); Canadian Rapid Treatment Center of Excellence, Mississauga, Ontario (Rosenblat, Kratiuk); Department of Psychiatry and Behavioral Sciences, Austin Dell Medical School, University of Texas, Austin (Nemeroff); Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (Sanacora); Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, and Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York (Murrough); Deakin University, Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia (Berk, Dodd); Orygen, National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Melbourne, Australia (Berk); Department of Psychiatry, Queen's University School of Medicine, and Centre for Neuroscience Studies, Queen's University, Kingston, Ontario (Brietzke); Centre for Youth Mental Health and Department of Psychiatry, University of Melbourne, Melbourne, Australia (Dodd); Université de Paris, Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, and GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris (Gorwood); Department of Psychological Medicine, Yong Loo Lin School of Medicine, and Institute of Health Innovation and Technology, National University of Singapore, Singapore (Ho); Department of Psychiatry, NYU School of Medicine, and Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York (Iosifescu); Department of Psychiatry, Universidad de Antioquia, Medellin, Colombia (Lopez Jaramillo); Center for Brain Research, Medical University of Vienna, Vienna (Kasper); Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland (Kratiuk); Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Paik Institute for Clinical Research, and Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea (J.G. Lee); Institute of Medical Science, University of Toronto, Toronto (Y. Lee); Clinical Trials Network and Institute, Massachusetts General Hospital, Boston (Papakostas); Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, and Corporal Michael J. Crescenz VA Medical Center, Philadelphia (Thase); Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona (Vieta); Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London and South London, and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, Kent (Young); Experimental Therapeutics and Pathophysiology Branch and Section on the Neurobiology and Treatment of Mood Disorders, Division of Intramural Research Program, NIMH, Bethesda, Md. (Zarate); Department of Psychiatry and Neuroscience, University of California, Riverside, and University of California, San Diego (Stahl).

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.
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http://dx.doi.org/10.1176/appi.ajp.2020.20081251DOI Listing
March 2021

Management of cognitive impairment in bipolar disorder: a systematic review of randomized controlled trials.

CNS Spectr 2021 Jan 28:1-22. Epub 2021 Jan 28.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.

Cognitive impairment is common in bipolar disorder and is emerging as a therapeutic target to enhance quality of life and function. A systematic search was conducted on PubMed, PsycInfo, Cochrane, clinicaltrials.gov, and Embase databases for blinded or open-label randomized controlled trials evaluating the pro-cognitive effects of pharmacological, neurostimulation, or psychological interventions for bipolar disorder. Twenty-two trials were identified, evaluating a total of 16 different pro-cognitive interventions. The methodological quality of the identified trials were assessed using the Cochrane Risk of Bias tool. Currently, no intervention (i.e., pharmacologic, neurostimulation, cognitive remediation) has demonstrated robust and independent pro-cognitive effects in adults with bipolar disorder. Findings are preliminary and methodological limitations limit the interpretation of results. Methodological considerations including, but not limited to, the enrichment with populations with pre-treatment cognitive impairment, as well as the inclusion of individuals who are in remission are encouraged. Future trials may also consider targeting interventions to specific cognitive subgroups and the use of biomarkers of cognitive function.
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http://dx.doi.org/10.1017/S1092852921000092DOI Listing
January 2021

The effectiveness, safety and tolerability of ketamine for depression in adolescents and older adults: A systematic review.

J Psychiatr Res 2021 May 1;137:232-241. Epub 2021 Mar 1.

Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, M5T 1R8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada. Electronic address:

The majority of antidepressant medication trials have focused on adult populations (ages 18-65), with much less research in older and younger populations. Moreover, key differences in the efficacy and safety of antidepressants have been identified between these age groups. Ketamine has emerged as a promising new treatment for treatment resistant depression (TRD). The objective of this review is to summarize and synthesize the extant literature on the effectiveness, safety and tolerability of ketamine for depression in special age populations (age ≤18 and ≥ 60). Following PRISMA guidelines, a systematic review was performed, searching EMBASE, PsycInfo, and PubMed from inception through July 2020. Studies reporting the use of any ketamine formulation with variable routes of administration to treat clinically diagnosed depression in adolescents or older adults were included. Thirteen studies were included in the analysis and ten observed rapid (≤2 week latency) antidepressant effects following ketamine treatments, with better outcomes following larger, repeated doses, and in open-label rather than blinded settings. Two case reports in adolescents assessed measures of suicidal ideation and both found ketamine to effectuate rapid anti-suicidal effects. Ketamine appears to be safe and well-tolerated in adolescents and older adults. The small quantity, high heterogeneity, and generally low quality of available studies precludes statistical syntheses and significantly limits the strength of our conclusions. Preliminary proof-of-concept studies are promising, however, rigorously designed randomized controlled trials (RCTs) are still required to ascertain effectiveness, safety and tolerability in these groups.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.058DOI Listing
May 2021

A Systematic review of the validity of screening depression through Facebook, Twitter, Instagram, and Snapchat.

J Affect Disord 2021 05 8;286:360-369. Epub 2021 Feb 8.

Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore. Electronic address:

Background: The aim of this study was to determine the validity of using social media for depression screening.

Method: Article searches on PubMed and PsycINFO from database inception to August 20, 2019 were completed with a search string and filters.

Results: 15 articles made the inclusion criteria. Facebook, Twitter, and Instagram profiles of depressed people were distinguishable from nondepressed people shown by social media markers. Facebook studies showed that having fewer Facebook friends and mutual friends, posting frequently, and using fewer location tags positively correlated with depressive symptoms. Also, Facebook posts with explicit expression of depressive symptoms, use of personal pronouns, and words related to pain, depressive symptoms, aggressive emotions, and rumination predicted depression. Twitter studies showed that the use of "past focus" words, negative emotions and anger words, and fewer words per Tweet positively correlated with depression. Finally, Instagram studies showed that differences in follower patterns, photo posting and editing, and linguistic features between depressed people and nondepressed people could serve as a marker.

Limitations: The primary articles analyzed had different methods, which constricts the amount of comparisons that can be made. Further, only four social media platforms were explored.

Conclusion: Social media markers like number and content of Facebook messages, linguistic variability in tweets and tweet word count on Twitter, and number of followers, frequency of Instagram use and the content of messages on Instagram differed between depressed people and nondepressed people. Therefore, screening social media profiles on these platforms could be a valid way to detect depression.
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http://dx.doi.org/10.1016/j.jad.2020.08.091DOI Listing
May 2021

Efficacy of dextromethorphan for the treatment of depression: a systematic review of preclinical and clinical trials.

Expert Opin Emerg Drugs 2021 Mar 12;26(1):63-74. Epub 2021 Mar 12.

Department of Pharmacology, University of Toronto, Toronto, Canada.

Introduction: The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the need for mechanistically novel treatments. Convergent evidence implicates glutamatergic signaling as a potential therapeutic target in MDD.

Areas Covered: The synthesis herein of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and exhibits clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with MDD. DXM efficacy has been preliminarily reported in adults with bipolar depression. The combination of DXM and bupropion represents a pharmacokinetic and pharmacodynamic synergy which may account for the rapidity of action in MDD.

Expert Opinion: The combination of DXM and bupropion is a safe, well tolerated and efficacious treatment option in adults with MDD. Priority questions are whether DXM/bupropion is uniquely effective across discrete domains of psychopathology (e.g. anhedonia, reward processing, general cognitive systems) and/or whether it is able to significantly improve patient-reported outcomes (e.g. quality of life, psychosocial functioning). The availability of ketamine/esketamine and DXM/bupropion instantiates the relevance of glutamate as a treatment target in MDD. Studies in bipolar depression with DXM/bupropion are warranted as well as in MDD with suicidality.
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http://dx.doi.org/10.1080/14728214.2021.1898588DOI Listing
March 2021

Peripheral inflammatory biomarkers define biotypes of bipolar depression.

Mol Psychiatry 2021 Mar 3. Epub 2021 Mar 3.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.

We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.
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http://dx.doi.org/10.1038/s41380-021-01051-yDOI Listing
March 2021

Efficacy of Vortioxetine on Anhedonia: Results from a Pooled Analysis of Short-Term Studies in Patients with Major Depressive Disorder.

Neuropsychiatr Dis Treat 2021 22;17:575-585. Epub 2021 Feb 22.

Department of Psychiatry Products, H. Lundbeck A/S, Valby, Denmark.

Purpose: Anhedonia is a core symptom of major depressive disorder (MDD), which has important functional consequences for the patient. This post hoc analysis investigated the relationship between anhedonia and functioning in patients with MDD treated with vortioxetine.

Patients And Methods: We conducted a pooled analysis of all 11 short-term, double-blind, randomized, placebo-controlled studies of vortioxetine (fixed dose, 5-20 mg/day) in patients with MDD which included Montgomery-Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS) assessments. A short-term, randomized, active-controlled trial of flexible-dose treatment with vortioxetine (10-20 mg/day) versus agomelatine (25-50 mg/day) was also analyzed. Mean changes from baseline to study endpoint in MADRS total, MADRS anhedonia subscale, SDS total, and SDS social-functioning scores were analyzed by a mixed model for repeated measures. The relationship between treatment effects on anhedonia and functioning was investigated using path analysis.

Results: A total of 4988 patients with MDD were included in the placebo-controlled studies and 495 in the active-comparator study. Significant dose-dependent improvements in overall depressive symptoms, anhedonia, and measures of functioning were seen in vortioxetine-treated patients compared with those who received placebo or agomelatine. Results of the path analysis for the placebo-controlled studies suggested that the effect on functioning was mostly driven by the effect of treatment on MADRS anhedonia factors.

Conclusion: Vortioxetine showed significant short-term efficacy against anhedonia in this large population of patients with MDD. In the placebo-controlled studies, improvements in functioning associated with vortioxetine appeared to be mostly driven by the effect of treatment on MADRS anhedonia factors.
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http://dx.doi.org/10.2147/NDT.S296451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910099PMC
February 2021

Impact of Supplementation and Nutritional Interventions on Pathogenic Processes of Mood Disorders: A Review of the Evidence.

Nutrients 2021 Feb 26;13(3). Epub 2021 Feb 26.

Massachusetts General Hospital, Boston, MA 02114, USA.

This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists. Abnormal levels of folate, homocysteine, and SAMe have been shown to be associated with a higher risk of depression. Numerous studies have demonstrated antidepressant activity with L-methylfolate and SAMe supplementation in individuals with depression. Additionally, the amino acids L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, and L-tryptophan have been implicated in the development of depression and shown to exert antidepressant effects. Other agents with evidence for improving depressive symptoms include zinc, magnesium, omega-3 fatty acids, and coenzyme Q10. Potential biases and differences in study designs within and amongst the studies and reviews selected may confound results. Augmentation of antidepressant medications with various supplements targeting nutritional and physiological factors can potentiate antidepressant effects. Medical foods, particularly L-methylfolate, and other supplements may play a role in managing depression in patients with inadequate response to antidepressant therapies.
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http://dx.doi.org/10.3390/nu13030767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996954PMC
February 2021

Impact of SARS-CoV-2 Infection on Cognitive Function: A Systematic Review.

Front Psychiatry 2020 10;11:621773. Epub 2021 Feb 10.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.

The prevalence and etiology of COVID-19's impact on brain health and cognitive function is poorly characterized. With mounting reports of delirium, systemic inflammation, and evidence of neurotropism, a statement on cognitive impairment among COVID-19 cases is needed. A substantial literature has demonstrated that inflammation can severely disrupt brain function, suggesting an immune response, a cytokine storm, as a possible cause of neurocognitive impairments. In this light, the aim of the present study was to summarize the available knowledge of the impact of COVID-19 on cognition (i.e., herein, we broadly define cognition reflecting the reporting on this topic in the literature) during the acute and recovery phases of the disease, in hospitalized patients and outpatients with confirmed COVID-19 status. A systematic review of the literature identified six studies which document the prevalence of cognitive impairment, and one which quantifies deficits after recovery. Pooling the samples of the included studies (total sample = 644) at three standards of quality produced conservative estimates of cognitive impairment ranging from 43.0 to 66.8% prevalence in hospitalized COVID-19 patients only, as no studies which report on outpatients met criteria for inclusion in the main synthesis. The most common impairment reported was delirium and frequent reports of elevated inflammatory markers suggest etiology. Other studies have demonstrated that the disease involves marked increases in IL-6, TNFα, and IL-1β; cytokines known to have a profound impact on working memory and attention. Impairment of these cognitive functions is a characteristic aspect of delirium, which suggests these cytokines as key mediators in the etiology of COVID-19 induced cognitive impairments. Researchers are encouraged to assay inflammatory markers to determine the potential role of inflammation in mediating the disturbance of cognitive function in individuals affected by COVID-19.
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http://dx.doi.org/10.3389/fpsyt.2020.621773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902710PMC
February 2021

Loneliness-based impaired reward system pathway: Theoretical and clinical analysis and application.

Psychiatry Res 2021 Apr 10;298:113800. Epub 2021 Feb 10.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

Loneliness is a key determinant in the etiology of mental health disorders such as depression and has profound impacts on health, quality of life, and economic productivity. This narrative review uses extant neurobiology and evolutionary literature to propose a construct through which loneliness may induce depression in adulthood via the reward system (including symptom and treatment aspects). Early childhood (distal) factors were found to be important in influencing adult (proximal) factors, which lead to the formulation of the construct. Due to the heterogenous and comorbid nature of depression, a new subtype known as 'reward depression' was distinguished along with distinct symptoms to aid practitioners when assessing patient treatment options. Furthermore, an evolutionary perspective was applied to the current impaired reward construct to discuss how the ancestral purpose and environment (in terms of reward) clashes with the modern one. Finally, theoretical treatment and prevention ideas were examined and discussed, leading into future work that needs to build upon and confirm the outlined construct.
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http://dx.doi.org/10.1016/j.psychres.2021.113800DOI Listing
April 2021

Brain-derived neurotrophic factor levels in newly diagnosed patients with bipolar disorder, their unaffected first-degree relatives and healthy controls.

BJPsych Open 2021 Feb 16;7(2):e55. Epub 2021 Feb 16.

Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Centre Copenhagen, Rigshospitalet, Denmark; and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Background: Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives.

Aims: To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls.

Method: The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status.

Results: BDNF levels were found to be 22.0% (95% CI 1.107-1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007-1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05).

Conclusions: These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.
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http://dx.doi.org/10.1192/bjo.2021.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058924PMC
February 2021

Comparative efficacy of pharmacological treatments on measures of self-rated functional outcomes using the Sheehan Disability Scale in patients with major depressive disorder: a systematic review and network meta-analysis.

CNS Spectr 2021 Feb 15:1-9. Epub 2021 Feb 15.

Mood Disorders Psychopharmacology Unit, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

Objective: More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials.

Methods: PubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities.

Results: We included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low.

Conclusions: Our results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.
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http://dx.doi.org/10.1017/S1092852921000171DOI Listing
February 2021

Associations Among Screen Time, Sleep Duration and Depressive Symptoms Among Chinese Adolescents.

J Affect Disord 2021 04 2;284:69-74. Epub 2021 Feb 2.

Department of Medical statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:

Objectives: Relatively few studies have explored the inter-relationship between screen time (ST), sleep duration and depressive symptoms. The study herein sought to determine (1) the relationships between ST, sleep duration and depressive symptoms among Chinese adolescents; (2) whether sleep duration mediates the relationships between ST and depressive symptoms.

Methods: 1 grade students (n=1,976) from ten high schools in Guangzhou, China were invited through cluster sampling between January and April 2019. Self-reported ST with electronic devices and Internet, sleep duration, and The Center for Epidemiology Scale for Depression (CES-D) score were collected. Generalized mixed linear models and mediation analyses were conducted.

Results: There were 1,956 self-reported questionnaires received (response rate: 98.99%). Approximately 25% (471/1,929 for Internet use, 399/1,928 for electronic device) of the total sample reported ST >2 hours/day. Approximately 8.9% (169/1,894) reported a CES-D score >28. Longer ST with electronic devices (estimate=0.52, 95%CI: 0.24~0.80), Internet usage (estimate=0.82, 95%CI: 0.53~1.11) were positively associated with depressive symptoms, while less sleep (estimate=-1.85, 95%CI: -2.27~-1.43) was negatively associated with depressive symptoms. There is significant indirect effect of electronic device usage on depressive symptoms through sleep duration (indirect effect=0.08, 95%CI: 0.01~0.15).

Limitations: This study only included school students from Guangzhou. Causal relationship cannot be inferred by this cross-sectional design.

Conclusions: ST and sleep duration were significantly associated with depressive symptoms severity. The indirect effect of sleep duration suggests a possible mechanism of the association between ST and depressive symptoms. Future interventions to manage depressive symptoms should target sleep time and decrease ST among adolescents.
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http://dx.doi.org/10.1016/j.jad.2021.01.082DOI Listing
April 2021

Affective Temperament Traits Measured by TEMPS-A and Their Associations with Cognitive Functions among Offspring of Parents with Bipolar Disorder with and without Subthreshold Symptoms.

J Affect Disord 2021 03 2;283:377-383. Epub 2021 Feb 2.

Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, 510370, China; Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. Electronic address:

Background: To our knowledge, there have been no studies that have examined affective temperament traits in offspring of parents with bipolar disorder (BD). The aim of this study was to identify affective temperamental characteristics and their relationships with cognitive functions in BD offspring.

Methods: A group of BD offspring were enrolled in this study. Subthreshold symptoms were used to categorize participants as either symptomatic offspring (SO) (n=60) or asymptomatic offspring (AO) (n=52). Healthy controls (HCs; n=48) were also enrolled for comparison. We used the Chinese Short Version of Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire (TEMPS-A) to measure temperament traits, and MATRICS Consensus Cognitive Battery (MCCB) to measure cognitive functions.

Results: We observed higher cyclothymic, irritable, depressive and anxious temperament scores in SO than AO when compared to HCs. In BD offspring (SO and AO), cyclothymic individuals performed better in processing speed and verbal learning than depressive individuals and better in attention/vigilance than irritable and anxious individuals; hyperthymic individuals performed better in processing speed than depressive individuals. We also observed that a higher cyclothymic score was associated with better verbal learning and verbal fluency, a higher hyperthymic score was associated with better processing speed and verbal learning; while a higher depressive score was associated with worse processing speed, verbal learning and verbal fluency and a higher irritable score was associated with worse attention/vigilance.

Conclusions: The relationships between cognitive functions and measures of temperament suggest that these features may share neurobiological substrates and appear to be heritable.
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http://dx.doi.org/10.1016/j.jad.2021.01.061DOI Listing
March 2021

The impact of COVID-19 pandemic on physical and mental health of Asians: A study of seven middle-income countries in Asia.

PLoS One 2021 11;16(2):e0246824. Epub 2021 Feb 11.

Southeast Asia One Health University Network (SEAOHUN), Chiang Mai, Thailand.

The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p<0.05). Thailand had all the highest scores of IES-R, DASS-21 stress, anxiety, and depression scores whereas Vietnam had all the lowest scores. The risk factors for adverse mental health during the COVID-19 pandemic include age <30 years, high education background, single and separated status, discrimination by other countries and contact with people with COVID-19 (p<0.05). The protective factors for mental health include male gender, staying with children or more than 6 people in the same household, employment, confidence in doctors, high perceived likelihood of survival, and spending less time on health information (p<0.05). This comparative study among 7 MICs enhanced the understanding of metal health in the general population during the COVID-19 pandemic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246824PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877638PMC
February 2021

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study.

Transl Psychiatry 2021 Feb 5;11(1):111. Epub 2021 Feb 5.

Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China.

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049-0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.
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http://dx.doi.org/10.1038/s41398-021-01222-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864939PMC
February 2021