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Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5–20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [ P = 0.361, 95% confidence interval (CI) (−0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [ P < 0.001, 95% CI (−4.378, −2.323)] and HRQoL [ P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (−2.847, −0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted. [ABSTRACT FROM AUTHOR]

This article introduces a special issue of the Journal of Contemporary Issues in Education dedicated to honoring Professor Michael Marker, an Arapaho scholar and educator specializing in Indigenous education. The articles in this issue explore themes such as decolonizing education, Indigenous resistances, and the importance of place and land-based knowledge. The authors emphasize the need to amplify Indigenous voices and challenge Eurocentric academic practices. The articles use various mediums to convey their perspectives and promote alternative ways of knowing and educating, particularly through Indigenous perspectives and practices. [Extracted from the article]

Background: Insulin resistance (IR) is a potential predictor of antidepressant treatment response. Aims: We assess changes in IR after antidepressant treatment and whether these changes have any effect on treatment response. Also, to see whether changes in IR mediates relationship between C-reactive protein (CRP) and antidepressant efficacy. Methods: This is a secondary analysis of an 8-week, open-label clinical trial with 95 adults experiencing a major depressive episode. Response to vortioxetine was measured using the Montgomery–Åsberg Depression Rating Scale (MADRS). Generalized estimating equation models were utilized for this intent-to-treat analysis. Results: When adjusted for age, sex, and body mass index, there was a significant increase in IR following treatment in the overall sample (p = 0.035). This finding was detected in treatment non-responders (p = 0.019), whereas it was not observed in responders (p = 0.329). Mediation analysis revealed that change in IR during treatment was responsible for change in MADRS as well as the relationship between baseline CRP and treatment response. Conclusions: Exacerbation of IR during antidepressant treatment mediated non-response. Conversely in treatment responders IR reduced. Like previous studies, baseline CRP moderated treatment response. This relationship was also mediated by changes in IR. These findings further elucidate the role of IR in terms of antidepressant response as well as potentially explain inflammation's relationship with the latter. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real‐world effectiveness of repeated ketamine infusions for treatment‐resistant bipolar depression. Methods: This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment‐resistant bipolar I/II depression (n = 66) received four sub‐anesthetic doses of IV ketamine (0.5–0.75 mg/kg) over a two‐week period. Symptoms of depression, suicidality, anxiety, and functioning were assessed with validated self‐report measures. Results: Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology‐Self Report‐16 (QIDS‐SR16) with further reductions in depressive symptoms observed after each subsequent infusion (n = 66; mean QIDS‐SR16 reduction of 6.08+/−1.39; p < 0.0001). Significant reductions of suicidal thoughts (QIDS‐SR16‐Suicide Item) and anxiety (Generalized Anxiety Disorder‐7) were also observed with functional improvements on the Sheehan Disability Scale (p < 0.0001 on all measures). Moreover, the response rate (QIDS‐SR16 total score decrease ≥50% from baseline) was 35% and remission rate (QIDS‐SR16 total score ≤5) was 20% after four infusions. Infusions were generally well tolerated with treatment‐emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis. Conclusions: Real‐world effectiveness of IV ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability. [ABSTRACT FROM AUTHOR]

Summary: Sleep disturbances are commonly reported in patients with treatment‐resistant depression (TRD). Available data have shown that intravenous (IV) ketamine is an effective treatment for patients with TRD and growing data suggest ketamine may improve overall sleep architecture. In the present study, we evaluated whether changes in sleep symptoms mediated the anti‐depressive and/or anti‐suicidal effects of IV ketamine and whether improvement in sleep correlated with a higher likelihood of achieving response or remission. Adults with TRD received four infusions of IV ketamine at a community‐based clinic. Total depressive symptom severity was measured with the Quick Inventory Depressive Symptoms Self‐Report 16‐Item (QIDS‐SR16) at baseline and was repeated across four infusions. Suicidal ideation (SI) and four sleep symptoms were measured using the SI item and the five sleep items on the QIDS‐SR16. A total of 323 patients with TRD received IV ketamine. Self‐reported improvements in insomnia, night‐time restlessness, hypersomnia, early morning waking, and total sleep were significant partial mediators to the improvements observed in depression severity. Similarly, insomnia, night‐time restlessness, early morning waking and total sleep improvements mediated the reduction of IV ketamine on SI. All sleep items, except for hypersomnia, were associated with an increased likelihood of achieving response or remission. Notably, each point improvement in total sleep score was significantly associated with achieving responder/remitter status (odds ratio 3.29, 95% confidence interval 2.00–5.41). Insomnia, sleep restlessness, early morning waking and total sleep improvements were significant mediators of antidepressant and anti‐suicidal improvements in patients with TRD receiving IV ketamine. [ABSTRACT FROM AUTHOR]

Incretin-based treatments, such as glucagon-like peptide-1 receptor (GLP-1R) agonists (eg liraglutide and semaglutide), have rapidly transformed obesity treatment. The well-documented weight loss effect from these agents is considered to be primarily a result of their actions on food intake, but frequent anecdotal reports from varied sources have suggested that they might also broadly affect consummatory behavior, including alcohol and drugs of abuse, suggesting a potential modulatory effect on reward behavior. Herein, we critically review the extant literature on the behavioral effects of GLP-1R agonists in humans, including their impact on feeding behavior, alcohol/drug intake, and overall reward response. We also consider the physiological and neurobiological underpinnings of GLP-1 actions, with a focus on its distinct central and peripheral roles, as well as its relationships with the broader energy homeostasis network. We conclude with a discussion on the implications of this line of research on how behavior is conceptualized, and the potential future directions for research.

Background: Abnormalities in effort-based decision-making have been consistently reported in major depressive disorder (MDD). Evidence indicates that metabolic factors, such as insulin resistance and dyslipidemia, which are highly prevalent in MDD, are independently associated with reward disturbances. Herein, we investigate the moderating effect of metabolic factors on effort-based decision-making in individuals with MDD., Methods: Forty-nine adults with MDD completed the Effort Expenditure for Rewards Task (EEfRT). Anthropometric and laboratorial parameters were assessed in all participants. We conducted a factor analysis to identify combinations of correlated metabolic variables, and reduce the number of comparisons., Results: Proxy markers of elevated insulin resistance (OR: 0.816, p < 0.001) and hyperglycemia (OR: 0.898, p = 0.021) were associated with a lower willingness to exert physical effort for rewards in the EEfRT. In contrast, elevated HDL (OR: 1.165, p = 0.004), and elevated non-HDL cholesterol and triglycerides (OR: 1.184, p < 0.001) were associated with increased frequency of hard task choices. These associations were independent of age, sex, depressive symptoms severity and medication use. Computational modeling revealed that the insulin resistance (β = 0.275, p = 0.035) and cholesterol factors (β = 0.565, p < 0.001) were independently associated with increased effort discounting., Limitations: Post-hoc analysis using a relatively small sample of convenience., Conclusions: Metabolic factors significantly and independently modulated effort-based decision-making in patients with MDD. These results have implications for our understanding of reward disturbances in MDD, and offer insights for further mechanistic investigations., Competing Interests: Declaration of competing interest RBM has received research grant support from the CIHR, the PSI Foundation, and the Baszucki Brain Research Fund and an Academic Scholars Award, Department of Psychiatry, University of Toronto. CDL has received the support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is “LCF/BQ/EU22/11930062”. CDL has also received CME-related honoraria, or consulting fees from CASEN Recordati, Organon, Lundbeck, and the Academy for Continuing Medical Education (Akademijazakme), with no financial or other conflicts of interest relevant to the subject of this article.’ JDR has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services, Inc. (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Center for Mental Health, Joseph M. West Family Memorial Fund, and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion, Braxia Health, Braxia Scientific Corp., and COMPASS. RSM has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals,Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: It remains unclear whether subjective and objective measures of cognitive function in Post COVID-19 Condition (PCC) are correlated. The extent of correlation has mechanistic and clinical implications., Methods: This post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial contains baseline data of subjective and objective measures of cognition in a rigorously characterized cohort living with PCC. Herein, we evaluated the association between subjective and objective condition function, as measured by the Perceived Deficits Questionnaire, 20-item (PDQ-20) and the Digit Symbol Substitution Test (DSST) and Trails Making Test (TMT)-A/B, respectively., Results: A total of 152 participants comprised the baseline sample. Due to missing data, our statistical analyses included 150 for self-reported PDQ-20, 147 individuals for combined DSST-measured cognitive function (composite z-score of the Pen/Paper plus Online CogState Version, N combinedDSST ), 71 for in-person DSST-measured cognitive function (Pen/Paper Version), 70 for TMT-A-measured cognitive function, and 70 for TMT-B-measured cognitive function. After adjusting for age, sex, and education, PDQ-20 was significantly correlated with pen-and-paper DSST (β = -0.003, p = 0.002) and TMT-B (β = 0.003, p = 0.008) scores, but not with TMT-A scores (β = -0.001, p = 0.751)., Conclusions: Overall, a statistically significant correlation was observed between subjective and objective cognitive functions. Clinicians providing care for individuals with PCC who have subjective cognitive function complaints may consider taking a measurement-based approach to cognition at the point of care that focuses exclusively on patient-reported measures.

Background: Postpartum depression (PPD) is a severe, debilitating mood disorder with consequences for both mothers and children, highlighting the need for rapid-acting and effective treatments for PPD. The aim of this narrative review is to synthesize the available literature on the administration of ketamine for PPD and propose ketamine as a viable and advantageous treatment., Methods: A search was conducted on MEDLINE/PubMed, PsycInfo, and Embase databases from inception to October 10, 2021 for preclinical studies, interventional studies (ie, open-label and randomized controlled trials), as well as systematic reviews and meta-analyses evaluating the use of ketamine in postpartum populations. Completed and ongoing clinical trials were identified on ClinicalTrials.gov., Results: Four clinical trials were identified. Results from this review support additional investigation into ketamine as a potential treatment for PPD., Conclusions: Ketamine may be a favorable option for treating PPD due to its antidepressive and analgesic effects, short infusion time, and rapid clearance from the maternal bloodstream. However, there is insufficient evidence to support its use in this population, underscoring the importance of additional clinical research investigating ketamine for PPD.