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Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period.

The objective of the current study was to assess the association between adverse childhood experiences (ACEs) and irritable bowel syndrome (IBS) in mood disorder patients. Self-report data from the International Mood Disorders Collaborative Project were cross-sectionally analyzed to compare rates of IBS in participants with confirmed diagnoses of major depressive disorder (MDD; n = 279) or bipolar disorder (BD; n = 219). Data was sub-grouped and compared based on history of ACEs. In total, 69 of the 498 participants reported a diagnosis of IBS (13.8%). BD was associated with significantly elevated rates of IBS compared to MDD (18.5% versus 10.1% respectively). After adjusting for age and sex, history of childhood sexual abuse was associated with increased rates of IBS in mood disorder participants [adjusted odds ratio (aOR) = 1.95]. In the MDD subgroup, ACEs (all categories and individual categories) were not associated with increased rates of IBS. In the BD subgroup, history of childhood sexual abuse was associated with significantly increased rates of IBS (38% versus 14%; aOR = 3.7). In summary, BD was associated with a higher prevalence of IBS compared to MDD. Additionally, history of sexual abuse was associated with an increased prevalence of IBS in BD, but not in MDD.

Approximately 0.35-1% of the general population is afflicted with psychotic depression at some time in their life. Psychotic depression is a subtype of major depressive disorder characterized by mood congruent hallucinations and/or delusions. Patients with psychotic depression often represent the most severe cases, with high relapse and mortality rate. Although treatment guidelines recommend a combination of antidepressants and antipsychotics or electroconvulsive therapy, most patients subsequently relapse due to treatment resistance. Furthermore, with the concern of antipsychotic drug's side effects (e.g., tardive dyskinesia), there is a need for an alternative pharmacotherapy for psychotic depression. Recently, several case studies demonstrated that treatment with ketamine not only ameliorated mood, but also improved psychotic symptoms in patients with treatment-resistant depression and psychotic features. However, the safety of ketamine in these patients is controversial since ketamine is known to induce psychotomimetic and dissociative effects. Additionally, the efficacy and safety of ketamine in patients with psychotic depression has not been established as most clinical trials have excluded these persons due to the theorized risk of aggravating psychotic symptoms. Notwithstanding, it is not established empirically that ketamine treatment in psychotic depression would predictably amplify psychotic symptoms and/or overall illness presentation. Future trials evaluating ketamine in depression should include patients with psychotic features to inform whether ketamine is safe and effective in this subpopulation.

Ketamine may exert pro-cognitive effects on select measures of cognition in adults with mood disorders. We evaluated the effectiveness of intravenous (IV) ketamine on cognition in 68 adult outpatients with treatment-resistant depression (TRD) at the Canadian Rapid Treatment Center of Excellence between July 3, 2018 and April 16, 2020 (NCT04209296). Eligibility criteria for the present retrospective study included: primary diagnosis of major depressive or bipolar disorder; currently depressed; and insufficient response to two or more prior treatments. Participants received four infusions of ketamine hydrochloride (0.5-0.75 mg/kg) over 1-2 weeks. We assessed objective and subjective measures of cognition before and after two infusions, i.e., Digit Symbol Substitution Test (DSST), Trail Making Test-B (TMT-B), Patient Deficits Questionnaire, 5-item (PDQ-5-D). Ketamine significantly improved DSST (effect size [ES]=0.60), TMT-B (ES=0.84), as well as PDQ-5-D scores (ES=0.63), indicative of a moderate-to-large effect size. Improvements in DSST and PDQ-5-D with ketamine were mediated by reductions in depressive symptoms, whereas improvements in TMT-B were independent of changes in depressive symptoms. Our results support the independent, rapid-onset, pro-cognitive effects with IV ketamine in adults with TRD. Larger, randomized, controlled trials with ketamine wherein cognition is the primary outcome measure in mood and non-mood disorder samples are warranted.

Numerous clinical trials have reported that intravenous (IV) ketamine demonstrates rapid antidepressant and anti-suicidal effects in patients with treatment-resistant depression (TRD). These studies, however, have not characterized whether these antidepressant effects translate to improvements in workplace productivity and functionality. Adults with TRD received repeated doses of IV ketamine at a community-based clinic (n = 171). We evaluated patient outcomes at two timepoints of interest: (1) acute-phase (i.e., following 4–6 infusions, 17.6 ± 12.6 days from baseline) and (2) maintenance-phase (i.e., following 7–10 infusions, 153.9 ± 63.4 days from baseline). The primary outcome measure was change from baseline to maintenance-phase scores on the Sheehan Disability Scale (SDS) workplace/school item as well as days underproductive (i.e., presenteeism) and days lost (i.e., absenteeism). Secondary measures included the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). There was a significant reduction in workplace/school disability, and significantly reduced symptoms of presenteeism and absenteeism. At the acute-phase outcome, this translated to 2 more days of productivity and 1.5 less days absent from work. Additionally, IV ketamine exhibited a sustained antidepressant effect across the ten infusions. IV ketamine was associated with a significant reduction in workplace/school disability and demonstrated improvements in symptoms of presenteeism and absenteeism.

Antidepressant pharmacotherapy dominates current treatment in psychiatry, including treatment for major depressive disorder (MDD). However, the current trial-and-error process of medication selection contributes to treatment failure and unnecessarily exposes patients to lengthy and insufficient treatment trials. Notably, improvements in measures of cognition have been demonstrated to occur early during treatment and prior to improvements in clinical state. Cognitions have been categorized based on emotional valence (i.e., cold versus hot cognitions). Cold cognitions describe cognitive operations that are relevant to the processing of non-emotional information. The current analysis investigates whether early changes in cold cognition can predict response after 8 weeks of vortioxetine treatment in adults with MDD. This was secondary analysis of an 8-week, open-label study. Cognition was assessed at week 0 and week 2 to measure early cognitive change. Depressive symptom severity was assessed at week 0 and week 8 to measure treatment response. Eighty-one subjects were analyzed using binomial logistic regression models. Early change in cognition was a non-significant predictor of response (p = 0.845, SE = 0.599, OR = 1.124), which may have resulted from high data variability. The overall predictive accuracy of the model was low (sensitivity = 37.5%, specificity = 89.8%, PPV = 70.6%, NPV = 68.8%). Future studies should include larger samples and stratify patients based on potentially moderating variables, such as baseline cognitive impairment and occupation. Stratification would likely produce more homogenous samples, reducing the amount of variability observed for early cognitive change.

While moderate to vigorous physical activity may be one method of addressing common physical morbidities in schizophrenia, reducing sedentary time may be a low intensity adjunct. In order to determine whether sedentary behaviour is associated with health outcomes, valid and reliable tools for assessing sedentary time are necessary. In order to characterize the validity and reliability of the International Physical Activity Questionnaire (IPAQ) for assessing sitting (sedentary) time, participants completed the IPAQ at baseline and 4 weeks later and wore accelerometers for 7 days before the final assessment. Bland-Altman analyses and intraclass correlation coefficients (ICC) were used to compare agreement between measurements. One-hundred thirteen individuals completed the study. Mean difference between the IPAQ and accelerometer was 26.8 min (95% Limits of Agreement: −458.7–512.3) and ICCA,1 was 0.23 (95% CI: 0.06–0.39). Week 1 and Week 4 administrations of the IPAQ differed by an average of 26.6 min, (95% Limits of Agreement: −510.9–564.2) and ICCA,1 was 0.41 (95% CI: 0.21–0.59). The “minutes” of sitting reported by the IPAQ do not reflect objective sedentary behaviour measurements and this current measure may be unsuitable for the population level assessment of sitting time among individuals with schizophrenia.

Cognitive impairment represents a significant source of disability among individuals with schizophrenia. Therefore, the aim of this study was to investigate, at a proof-of-concept level, whether one single bout of exercise can improve executive function among these individuals. In this within-participant, counterbalanced experiment, participants with schizophrenia ( n =36) completed two sessions (cycling at moderate-intensity and passively sitting) for 20 min, with a one-week washout period between the two sessions. Participants completed the Wisconsin Card Sorting Test (WCST) before and after each session to measure changes in executive function. The inclusion of both sessions completed by each participant in the analyses revealed a significant carryover effect. Consequently, only the WCST scores from the first session completed by each participant was analyzed. There was a significant time by session interaction effect for non-perseverative errors. Post-hoc Tukey's HSD contrasts revealed a significant reduction in non-perseverative errors in the exercise group that was of moderate-to-large effect. Furthermore, there was also a moderate between-group difference at post-testing. Therefore, an acute bout of exercise can improve performance on an executive function task in individuals with schizophrenia. Specifically, the reduction in non-perseverative errors on the WCST may reflect improved attention, inhibition and overall working memory.