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Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p β*(95% CI) = 0.38 (0.23, 0.54); p r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630

Background Subanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment. Methods Thirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report. Results Twenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37–0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η p2 = 0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P Conclusion A short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier NCT01945047

Background Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine’s specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings. Methods Data for this participant-level integrative data analysis were drawn from 151 participants across 10 studies, and linear regression was used to examine the relationship between placebo response for suicidal ideation vs other depressive symptoms indexed from standard rating scales—specifically, depressed mood, anhedonia, anxiety, and guilt—over time. Results For participants receiving saline placebo (n = 46), greater placebo response was observed for suicidal ideation compared with other symptoms indexed from standard depression rating scales, except for anxiety. For those receiving midazolam placebo (n = 105), greater placebo response was observed for suicidal ideation compared with depressed mood or anhedonia, and no significant differences were observed when comparing suicidal ideation with anxiety or guilt. Conclusions Taken together, the results provide preliminary evidence of a differential placebo response for suicidal ideation vs other depressive symptoms, while anxiety and suicidal ideation appear to produce similar placebo response profiles. These findings may help explain the more modest findings in clinical IV ketamine trials for suicidal ideation than overall depression.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused global disruptions with serious psychological impacts. This study investigated the emergence of new psychiatric symptoms and the worsening of pre-existing mental disorders during the COVID-19 pandemic, identified factors associated with psychological worsening, and assessed changes in mental health service use. Methods: An online survey was circulated between April 3 and June 23, 2020. Respondents were asked to complete mental health questionnaires based on 2 time referents: currently (i.e., during the outbreak) and in the month preceding the outbreak. A total of 4,294 Canadians between 16 and 99 years of age were subdivided based on the presence of self-reported psychiatric diagnoses. Results: The proportion of respondents without prior psychiatric history who screened positive for generalized anxiety disorder and depression increased by 12% and 29%, respectively, during the outbreak. Occurrences of clinically important worsening in anxiety, depression, and suicidal ideation symptoms relative to pre-outbreak estimates were significantly higher in those with psychiatric diagnoses. Furthermore, 15% to 19% of respondents reported increased alcohol or cannabis use. Worse psychological changes relative to pre-outbreak estimate were associated with female sex, younger age, lower income, poorer coping skills, multiple psychiatric comorbidities, previous trauma exposure, deteriorating physical health, poorer family relationships, and lower exercising. Reductions in mental health care were associated with increased suicidal ideation. Conclusion: The worsening in mental health symptoms and the decline in access to care call for the urgent development of adapted interventions targeting both new mental disorders and pre-existing psychiatric conditions affected by the COVID-19 pandemic.

Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions.Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control). After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered thrice weekly over 2 weeks. Responders, classified as those participants who had a ≥50% decrease in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), received four additional infusions administered once weekly (maintenance phase).Compared with midazolam, a single ketamine infusion elicited a significantly greater reduction in depressive symptoms at the primary efficacy endpoint (24 hours postinfusion). Linear mixed models revealed cumulative antidepressant effects with repeated infusions and doubling of the antidepressant response rate. Fifty-nine percent of participants met response criteria after repeated infusions, with a median of three infusions required before achieving response. Participants had no further change in MADRS scores during weekly maintenance infusions.Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings.

Sub-anesthetic ketamine doses rapidly reduce depressive symptoms, although additional investigations of the underlying neural mechanisms and the prediction of response outcomes are needed. Electroencephalographic (EEG)-derived measures have shown promise in predicting antidepressant response to a variety of treatments, and are sensitive to ketamine administration. This study examined their utility in characterizing changes in depressive symptoms following single and repeated ketamine infusions.Recordings were obtained from patients with treatment-resistant major depressive disorder (MDD) (N = 24) enrolled in a multi-phase clinical ketamine trial. During the randomized, double-blind, crossover phase (Phase 1), patients received intravenous ketamine (0.5 mg/kg) and midazolam (30 μg/kg), at least 1 week apart. For each medication, three resting, eyes-closed recordings were obtained per session (pre-infusion, immediately post-infusion, 2 h post-infusion), and changes in power (delta, theta1/2/total, alpha1/2/total, beta, gamma), alpha asymmetry, theta cordance, and theta source-localized anterior cingulate cortex activity were quantified. The relationships between ketamine-induced changes with early (Phase 1) and sustained (Phases 2,3: open-label repeated infusions) decreases in depressive symptoms (Montgomery-Åsberg Depression Rating Score, MADRS) and suicidal ideation (MADRS item 10) were examined.Both medications decreased alpha and theta immediately post-infusion, however, only midazolam increased delta (post-infusion), and only ketamine increased gamma (immediately post- and 2 h post-infusion). Regional- and frequency-specific ketamine-induced EEG changes were related to and predictive of decreases in depressive symptoms (theta, gamma) and suicidal ideation (alpha). Early and sustained treatment responders differed at baseline in surface-level and source-localized theta.Ketamine exerts frequency-specific changes on EEG-derived measures, which are related to depressive symptom decreases in treatment-resistant MDD and provide information regarding early and sustained individual response to ketamine.ClinicalTrials.gov: Action of Ketamine in Treatment-Resistant Depression, NCT01945047.

Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P

Objectives Inappropriate antibiotic use contributes to antimicrobial resistance. The SpectrumTM app provides antibiotic decision support, based on local antimicrobial resistance rates. We determined the impact of regional implementation of the app on inpatient antimicrobial appropriateness, inpatient antimicrobial usage (AMU), population-based Clostridioides difficile infection (CDI) rates and cost, using a retrospective, before and after quasi-experimental design, including a one-year study period. Methods The SpectrumTM app was released to prescribers in February, 2019. We performed two one-day inpatient point prevalence surveys using the National Antimicrobial Prescribing Survey tool, six months before (June 25, 2018) and six months after (June 25, 2019) app dissemination. Inpatient AMU in Defined Daily Dose/1000 patient days and CDI incidence were compared, before and after app dissemination. Results The pre-survey included 184 prescriptions, and the post-survey included 197 prescriptions. Appropriateness was 97/176 (55.1%) pre, and 126/192 (65.6%) post (+10.5%, p = 0.051). Inpatient AMU declined by 6.6 DDD/1000 patient days per month, and CDI declined by 0.3 cases per month. Cost savings associated with reduced AMU were $403.98/bed/year and associated with reduced CDI were $82,078/year. Conclusion We observed improvement in antimicrobial stewardship indicators following SpectrumTM implementation. We cannot determine the cause of these improvements.

Background: Global health crises, such as the COVID-19 pandemic, confront healthcare workers (HCW) with increased exposure to potentially morally injurious events. The pandemic has provided an opportunity to explore the links between moral distress, moral resilience, and emergence of mental health symptoms in HCWs. Methods: A total of 962 Canadian healthcare workers (88·4% female, 44·6 + 12·8 years old) completed an online survey during the first COVID-19 wave in Canada (between April 3 rd and September 3 rd , 2020). Respondents completed a series of validated scales assessing moral distress, perceived stress, anxiety, and depression symptoms, and moral resilience. Respondents were grouped based on exposure to patients who tested positive for COVID-19. In addition to descriptive statistics and analyses of covariance, multiple linear regressions were used to evaluate association between moral resilience, demographic/professional factors and moral distress and to identify factors associated with moral resilience. Findings: Respondents working with patients with COVID-19 showed significantly more severe moral distress, anxiety and depression symptoms (F > 5·5, p 9·1, p = ·002), compared to healthcare workers who were not. Higher exposure to potentially morally injurious events (B=2·98, 95% CI [2·90, 3·05]) and lower moral resilience (B=3·12, 95% CI [0·04, 6·20]) were associated with worse moral distress. Moral resilience moderated the relationship between exposure to potentially morally injurious events and moral distress (p ·27, p

IntroductionThe negative impacts of COVID-19 have rippled through every facet of society. Understanding the multidimensional impacts of this pandemic is crucial to identify the most critical needs and to inform targeted interventions. This population survey study aimed to investigate the acute phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress between 3 April and 15 May 2020.Methods6040 participants are included in this report. A multivariate linear regression model was used to identify factors associated with stress changes (as measured by the Cohen’s Perceived Stress Scale (PSS)) relative to pre-outbreak retrospective estimates.ResultsOn average, PSS scores increased from low stress levels before the outbreak to moderate stress levels during the outbreak (pConclusionCross-sectional analyses showed a significant increase from low to moderate stress during the COVID-19 outbreak. Identified modifiable factors associated with increased stress may be informative for intervention development.Trial registration numberNCT04369690; Results.

Using electronic medical record (EMR) data collected from psychiatric inpatient admissions, the objective of this study was to identify sex differences in risk factors for presence of suicide plans and/or attempts within the 30 days preceding hospital admission. Resident Assessment Instrument for Mental Health (RAI-MH) intake data were obtained for patients admitted to a Canadian tertiary-care hospital deemed a ‘threat or danger to self’ during a ten-year period (2008-2018). Data was extracted for individuals categorized into three groups: non-suicidal (N=568), presence of suicide plan (N=178), and presence of suspected suicide attempt (N=124) in the 30 days prior to hospital admission. A multivariate logistic regression revealed that younger age (odds ratio=0.97), female sex (OR=1.56), disrupted family relationships (OR=1.54), recent stressors (OR=1.59), participation in social activities (OR=1.54), having no confidant (OR=1.55), and diagnosis of depressive disorder (OR=5.54) increased the odds of suicide plan and/or attempt in the 30 days prior to hospital admission. Stratifying the regression model by sex highlighted different risk factors for suicide plan and attempt specific to males and females. EMR-derived findings highlight psychosocial and clinical determinants associated with suicide plan or attempt prior to psychiatric admission that differ according to sex.

BackgroundUnderstanding the multifaceted impacts of the Coronavirus-19 (COVID-19) outbreak as it unfolds is crucial to identify the most critical needs and to inform targeted interventions.MethodsThis population survey study presents cohort characteristics and baseline observations linked to the acute-mid phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress as measured by the Cohen’s Perceived Stress Scale (PSS) collected cross-sectionally between April 3 and May 15, 2020. A multivariate linear regression model was used to identify factors associated with stress changes relative to pre-outbreak estimates.Findings6,040/6,685 (90·4%) participants filled out at least 1/3 of the survey and were included in the analyses. On average, PSS scores increased from 12·9+6·8 before the outbreak to 14·9+8·3 during the outbreak (pInterpretationCross-sectional analyses showed a significant increase from average low to moderate stress during the COVID-19 outbreak. Identified modifiable factors associated with an increase in stress may be informative for intervention development.

Background Recent evidence underscores the utility of rapid-acting antidepressant interventions, such as ketamine, in alleviating symptoms of major depressive episodes (MDE). However, to date, there have been limited head-to-head comparisons of intravenous (IV) ketamine infusions with other antidepressant treatment strategies in large randomized trials. This study protocol describes an ongoing multi-centre, prospective, randomized, crossover, non-inferiority trial comparing acute treatment of individuals meeting diagnostic criteria for a major depressive episode (MDE) with ketamine and electroconvulsive therapy (ECT) on efficacy, speed of therapeutic effects, side effects, and health care resource utilization. A secondary aim is to compare a 6-month maintenance strategy for ketamine responders to standard of care ECT maintenance. Finally, through the measurement of clinical, cognitive, neuroimaging, and molecular markers we aim to establish predictors and moderators of treatment response as well as treatment-elicited effects on these outcomes. Methods Across four participating Canadian institutions, 240 patients with major depressive disorder or bipolar disorder experiencing a MDE are randomized (1:1) to a course of ECT or racemic IV ketamine (0.5 mg/kg) administered 3 times/week for 3 or 4 weeks. Non-responders ( Discussion This multi-centre study will help identify molecular, imaging, and clinical characteristics of patients with treatment-resistant and/or severe MDEs who would benefit most from either type of therapeutic strategy. In addition to informing clinical practice and influencing health care delivery, this trial will add to the robust platform and database of CAN-BIND studies for future research and biomarker discovery. Trial registration ClinicalTrials.gov identifier NCT03674671. Registered September 17, 2018.

Oligodendrocyte progenitor cells (OPCs) are a mitotically active population of glia that comprise approximately 5% of the adult brain. OPCs maintain their proliferative capacity and ability to differentiate in oligodendrocytes throughout adulthood, but relatively few mature oligodendrocytes are produced following developmental myelination. Recent work has begun to demonstrate that OPCs likely perform multiple functions in both homeostasis and disease, and can significantly impact behavioral phenotypes such as food intake and depressive symptoms. However, the exact mechanisms through which OPCs might influence brain function remains unclear. In this work, we demonstrate that OPCs are transcriptionally diverse and separate into three distinct populations in the homeostatic brain. These three groups show distinct transcriptional signatures and enrichment of biological processes unique to individual OPC populations. We have validated these OPC populations using multiple methods, including multiplex RNA in situ hybridization and RNA flow cytometry. This study provides an important resource that profiles the transcriptome of adult OPCs and will provide a significant foundation for further investigation into novel OPC functions.

Background: Understanding the multifaceted impacts of the Coronavirus-19 (COVID-19) outbreak as it unfolds is crucial to identify the most critical needs and to inform targeted interventions. Methods: This population survey study presents cohort characteristics and baseline observations linked to the acute-mid phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress as measured by the Cohen's Perceived Stress Scale (PSS) collected cross-sectionally between April 3 and May 15, 2020. A multivariate linear regression model was used to identify factors associated with stress changes relative to pre-outbreak estimates. Findings: 6,040/6,685 (90·4%) participants filled out at least 1/3 of the survey and were included in the analyses. On average, PSS scores increased from 12·9+6·8 before the outbreak to 14·9+8·3 during the outbreak (p

A growing body of literature has shown the effectiveness of ketamine for treating chronic depression. How long the beneficial effects of repeated ketamine last once infusions are stopped, however, remains largely unknown. Understanding the challenges that ensue after ketamine cessation can help clinicians optimally guide patients who opt for ketamine treatment and minimize the associated risks. In this commentary, we discuss some unexpected data gathered from participants of a pilot study on the effects of adjunctive ketamine infusion for resistant depression.

ObjectiveIn major depressive disorder (MDD), single nucleotide polymorphisms (SNPs) in monoaminergic genes may impact disease susceptibility, treatment response, and brain volume. The objective of this study was to examine the effect of such polymorphisms on hippocampal volume in patients with treatment-resistant MDD and healthy controls. Candidate gene risk alleles were hypothesised to be associated with reductions in hippocampal volume.MethodsA total of 26 outpatients with treatment-resistant MDD and 27 matched healthy controls underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF)]. Hippocampal volume was estimated using an automated segmentation algorithm (FreeSurfer).ResultsHippocampal volume did not differ between patients and controls. Within the entire study sample irrespective of diagnosis, C allele-carriers for both the NET−182 T/C [rs2242446] and 5-HT1A−1019C/G [rs6295] polymorphisms had smaller hippocampal volumes relative to other genotypes. For the 5-HTTLPR (rs25531) polymorphism, there was a significant diagnosis by genotype interaction effect on hippocampal volume. Among patients only, homozygosity for the 5-HTTLPR short (S) allele was associated with smaller hippocampal volume. There was no association between the 5-HT2A, COMT, and BDNF SNPs and hippocampal volume.ConclusionThe results indicate that the volume of the hippocampus may be influenced by serotonin- and norepinephrine-related gene polymorphisms. The NET and 5-HT1A polymorphisms appear to have similar effects on hippocampal volume in patients and controls while the 5-HTTLPR polymorphism differentially affects hippocampal volume in the presence of depression.

The feeling of presence has been shown to be an important concept in several clinical applications of virtual reality. Among the factors influencing presence, realism factors have been examined extensively from the angle of objective realism. Objective realism has been manipulated by altering numerous technological characteristics such as pictorial quality, texture and shading, or by adding more sensory information (i.e., smell, touch). Much less studied is the subjective (or perceived) realism, the focus of the two pilot studies reported in this article. In Study 1, subjective realism was manipulated in order to assess the impact on the feeling of presence. Method: Presence was measured in 31 adults after two immersions in virtual reality. Participants were immersed in a neutral/irrelevant virtual environment and subsequently subjected to the experimental manipulation. Participants in the experimental condition were falsely led to believe that they were immersed live in real time in a ''real'' room with a ''real'' mouse in a cage. In the control condition, participants believed they were immersed in a replica of the nearby room. All participants were actually immersed in the exact same virtual environment. Results: A manipulation check revealed that 80% of the participants believed in the deception. A 2 Times by 2 Conditions repeated measure ANOVA revealed that leading people to believe they were seeing a real environment digitized live in virtual reality increased their feeling of presence compared to the control condition. In Study 2, the same experimental design was used but with simultaneous functional magnetic resonance imaging (fMRI) in order to assess brain areas potentially related to the feeling of presence. fMRI data from five participants were subjected to a within subject fixed effect analysis to verify differences between the experimental immersion (higher presence) and the control immersion (lower presence). Results revealed a statistically significant difference in left and right parahippocampus areas. Conclusion: Results are discussed according to layers of presence and consciousness and the meaning given to experiences occurring in virtual reality. Some suggestions are formulated to target core presence and extended presence.

Background Tibial plateau fractures (TPFs) are frequently associated with motor vehicle accidents, auto-pedestrian crashes and falls. However, hospitals near ski resorts commonly treat TPF resulting from skiing. The soft tissue envelope and original mechanism of injury are important determinants in the decision to proceed with immediate or delayed fixation of the fracture. Our objective was to assess whether immediate (≤24 hours) versus delayed (>24 hours) open reduction internal fixation (ORIF) affected in-hospital outcomes among snow sport participants. Methods This was a retrospective study of patients with isolated TPF who were injured while skiing or snowboarding and treated at a Level III Trauma Center that serves four major ski resorts between 2010 and 2013. Clinical characteristics and in-hospital outcomes were obtained from an existing trauma database. Imaging was reviewed to classify the fracture as high (Schatzker IV–VI) or low (Schatzker I–III) energy. Differences in clinical characteristics and outcomes between immediate and delayed ORIF patients were analyzed with χ2 and Wilcoxon two-sample tests. These analyses were also performed in the high-energy and low-energy fracture populations. Results ORIF was performed on 119 snow sport patients, 93 (78%) immediately. Patients had a median age of 49 years (range 19–70) and were predominantly male (66%). Forty percent sustained a high-energy TPF. No differences were observed between the demographic characteristics, injury severity, Schatzker scores or time from injury to hospital arrival for patients treated immediately versus delayed treatment. Compared with delayed fixation, patients treated immediately had less compartment syndrome (3% vs 27%), needed fewer fasciotomies (6% vs 31%) and had a shorter length of stay (3 vs 6.5 days), p

Episodic memory, related to the hippocampus, has been found to be impaired in schizophrenia. Further, hippocampal anomalies have also been observed in schizophrenia. This study investigated whether average hippocampal grey matter (GM) would differentiate performance on a hippocampus-dependent memory task in patients with schizophrenia and healthy controls. Twenty-one patients with schizophrenia and twenty-two control participants were scanned with an MRI while being tested on a wayfinding task in a virtual town (e.g., find the grocery store from the school). Regressions were performed for both groups individually and together using GM and performance on the wayfinding task. Results indicate that controls successfully completed the task more often than patients, took less time, and made fewer errors. Additionally, controls had significantly more hippocampal GM than patients. Poor performance was associated with a GM decrease in the right hippocampus for both groups. Within group regressions found an association between right hippocampi GM and performance in controls and an association between the left hippocampi GM and performance in patients. A second analysis revealed that different anatomical GM regions, known to be associated with the hippocampus, such as the parahippocampal cortex, amygdala, medial and orbital prefrontal cortices, covaried with the hippocampus in the control group. Interestingly, the cuneus and cingulate gyrus also covaried with the hippocampus in the patient group but the orbital frontal cortex did not, supporting the hypothesis of impaired connectivity between the hippocampus and the frontal cortex in schizophrenia. These results present important implications for creating intervention programs aimed at measuring functional and structural changes in the hippocampus in schizophrenia.

The Umatilla River Basin Fisheries Restoration Plan was initiated in the early 1980s to mitigate salmonid losses caused by hydroelectric development and habitat degradation. The objectives are to enhance the abundance of endemic steelhead and reintroduce extirpated chinook and coho salmon. The project prompted collaborative effort among federal, state, and tribal agencies, and local water users. It has incorporated habitat restoration, flow enhancement, fish passage improvements, and population supplementation through artificial production. Water exchanges have successfully increased minimum flows during spring and fall migration. While flows remain depressed compared to historic conditions, there is potential for improved habitat, passage, and homing. The mean adult-to-adult return rate of hatchery-reared steelhead exceeded replacement and that of the naturally-spawning population. Although the smolt-to-adult survival rates of hatchery-reared fish fluctuate, salmonid escapement has increased in recent years, permitting steelhead and spring chinook harvest. Enumeration of potential spawners and observed redds reveals an increase in natural production of all supplemented species. Comparison of hatchery-reared and naturally-spawning steelhead populations revealed differences in life history characteristics (in age composition and sex ratios) though run timing and genetic stock compositions of the two components of the populations have not differed. Sustained monitoring is needed to determine benefits of integrating habitat restoration and artificial production in restoring salmonid populations.

Intact episodic memory requires the ability to make associations between the contextual features of an event, referred to as contextual binding. Binding processes combine different contextual elements into a complete memory representation. It has been proposed that binding errors during the encoding process are responsible for the episodic memory impairments reported in schizophrenia. Since the hippocampus is critical for contextual binding and episodic memory, it was hypothesized that patients with schizophrenia would show a deficit in information processing in the hippocampus, measured with functional magnetic resonance imaging (fMRI). In the current experiment, 21 patients with schizophrenia and 22 healthy control participants were scanned while being tested on navigating in a virtual town (i.e. find the grocery store from the school), a task that was shown to be critically dependent on the hippocampus. Between-group comparisons revealed significantly less activation among patients relative to controls in the left middle frontal gyrus, and right and left hippocampi. We propose that the context and the content are not appropriately linked, therefore affecting the formation of a cognitive map representation in the patient group and eliciting a contextual binding deficit.

OBJECTIVE: Previous magnetic resonance imaging (MRI) studies have demonstrated brain-volume reductions in unipolar major depressive disorder (MDD). It is not clear whether these atrophic changes can be stabilized with antidepressant treatment and/or reversed with remission. The objective of this study was to prospectively examine brain-volume changes in patients with treatment-resistant depression, comparing those who achieved sustained remission with those who did not remit. METHOD: This prospective observational cohort study investigated the roles of clinical responsiveness and antidepressant treatment in lessening brain atrophy in depression. Data were collected between October 2004 and December 2008. Baseline MRI scans were obtained from 28 outpatients with treatment-resistant MDD (diagnosed according to DSM-IV criteria) who were recruited from the Mood Disorders Research Unit at the Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada. Twenty-seven patients underwent follow-up scanning after either 6 months of sustained remission (Montgomery-Asberg Depression Rating Scale score ≤ 12) or 12 months of failure to remit. Longitudinal whole-brain and voxel-based gray- and white-matter volume changes were estimated. RESULTS: Twelve patients (mean age at baseline = 47.5 years) achieved sustained 6-month remission. In contrast to nonremitters (n = 15; mean age at baseline = 44.3 years), remitted patients demonstrated a significant mean increase in whole-brain volume during follow-up (F(1,27) = 9.51, P = .005). Within-subject voxel-based morphometry analyses identified increased gray-matter volume in remitters in the right orbitofrontal cortex (t(11) = 7.61, P = .006) and the right inferior temporal gyrus (t(11) = 6.65, P = .004). Nonremitters showed decreased white-matter volume in the left anterior limb of the internal capsule (t(13) = 3.86, P = .04). CONCLUSIONS: Given that remitters exhibited a mean increase in brain volume while nonremitters lost volume, pharmacotherapy in the absence of sustained remission is most likely insufficient to elicit brain-volume increase in MDD. The findings suggest that clinical remission rather than pharmacotherapy may be the key factor involved in driving volumetric recovery in treatment-resistant depression. Language: en

Background: Magnetic resonance imaging studies have provided evidence of structural modifications in cortical-limbic regions in major depressive disorder. To date, however, few studies have tracked structural changes in patients during treatment. This prospective, longitudinal imaging study investigated associations between brain structure and clinical responsiveness in a sample of patients with treatment-resistant major depressive disorder during an approximate 1-year follow-up period. Methods: FreeSurfer software was used to extract volume or cortical thickness values from 6 regions of interest (hippocampus, rostral middle frontal gyrus, orbitofrontal cortex, rostral and caudal anterior cingulate cortices, and inferior temporal gyrus) in patients (n = 26) and matched healthy controls (n = 28). Regions of interest were selected based on previous evidence of potential associations between morphometric characteristics in these regions and treatment response or remission. Analyses were conducted to compare volume and cortical thickness in patients and controls at baseline imaging, determine whether patients’ brain structure at treatment initiation was associated with response over follow-up, and compare longitudinal changes in volume and cortical thickness in patients who achieved sustained 6-month remission (Montgomery-Asberg Depression Rating Scale Score ≤12) with nonremitters. Results: Patients and controls showed no structural differences at baseline. Among patients, thicker right caudal anterior cingulate cortex at baseline was associated with greater symptom improvement over follow-up. Remitters and nonremitters showed subtle changes in volume and thickness over time in opposing directions, with increased hippocampal volume and cortical thickness in the rostral middle frontal gyrus, orbitofrontal cortex, and inferior temporal gyrus in remitters, and decreased volume or thickness in these regions in nonremitters. Conclusions: The results suggest that longitudinal structural trajectories may differ in major depressive disorder patients according to their clinical response to treatment.

BackgroundElectronic prescribing (e-prescribing) can potentially help prevent medication errors. As the use of e-prescribing increases across Canada, understanding the benefits and gaps of early e-prescribing can help inform deployment of future e-prescribing systems. ObjectiveThe purpose of this exploratory study was to determine the prevalence of, reasons for, and average time taken for pharmacist clarification calls to prescribers for electronic medical record (EMR)-generated and handwritten prescriptions. MethodsFour community pharmacies in St John’s, Newfoundland, Canada prospectively collected information on clarification calls to prescribers for new prescriptions over a period of 17 to 19 weeks. Four semistructured interviews were conducted following the data collection period to gain further insight. ResultsAn estimated 1.33% of handwritten prescriptions required clarification compared with 0.66% of EMR-generated prescriptions. Overall, 1.11% of prescriptions required clarification with the prescriber. While illegibility was eliminated with EMR-generated prescriptions, clarification was still required for missing information (24%) and appropriateness (51%). Key themes, including errors unique to EMR-generated prescriptions, emerged from the qualitative interviews. ConclusionsAdvanced e-prescribing functionality will enable secure transmission of prescriptions from prescribers to a patient’s pharmacy of choice through a provincial electronic Drug Information System (DIS)/Pharmacy Network, which will lessen the need for clarification calls, especially in the domains of missing information and appropriateness of the prescription. This exploratory study provides valuable insight into the benefits and gaps of early e-prescribing. Advanced e-prescribing systems will provide an opportunity for further realization of quality and safety benefits related to medication prescribing.

The central goals of this manuscript are (1) to better characterize what appears to be the most parsimonious account of schizophrenic long-term memory impairment in the neuropsychological literature: a contextual binding deficit rooted in the medial temporal lobes; (2) to link this deficit to concrete abnormalities at the level of the hippocampus; and (3) to suggest that this deficit could lead to the functional impairment experienced by schizophrenia patients in their daily lives. As far as long-term memory is concerned in schizophrenia, there seems to be a general agreement to conclude that explicit mechanisms are disturbed compared to relatively spared implicit mechanisms. More precisely, both subsystems of explicit memory (i.e., episodic and semantic) appear to be dysfunctional in this patient population. Errors during the encoding processes could be responsible for this dysfunction even if retrieval per se is not totally spared. Recently, a number of studies have suggested that impairments in conscious recollection and contextual binding are closely linked to episodic memory deficit. Since the hippocampal formation is considered to be the central element in the neural support for contextual binding and episodic memory, we have conducted an extensive review of the literature concerning the hippocampal formation in schizophrenia. Emerging evidence from varying disciplines confirm the coherence of the different anomalies reported concurrently at the neuroanatomical, neurodevelopmental, biochemical, and genetic levels. It seems highly probable that the synaptic disorganization in the hippocampus concerns the regions crucial for encoding and contextual binding memory processes. The consequences of these deficits could result in schizophrenia patients experiencing major difficulties when facing usual events which have not been encoded with their proper context.

Impaired episodic memory (EM) has been reported in schizophrenia. Intact EM requires that contextual features be bound to the content of the event, a mechanism called contextual binding (CB). It is proposed that binding errors during the encoding process are responsible for EM impairments in schizophrenia. The hippocampal formation is considered the central element for CB, it is hypothesized that the synaptic disorganization described in this condition results in such a deficit. The main goals of these studies were to investigate the neurofunctioning, neuroanatomy and neurofunctional connectivity of the hippocampus while performing a task that used CB mechanisms. Spatial relational processing is part of CB and is rooted in the hippocampal region. Visuospatial navigation (wayfinding task), was used as a probe to activate the hippocampus and its associated regions in a group of patients with schizophrenia ( n =21) and matched healthy controls ( n =23). During the wayfinding task individuals with schizophrenia found landmarks less frequently, made more errors and took more time to complete the task. fMRI result indicated that the patient group had a hypofunctioning of the posterior part of the hippocampus while performing the wayfinding task. VBM results indicated that controls had significantly more hippocampal GM than patients and poor performances at the wayfinding task was associated with decreased right hippocampal GM for the overall group. Connectivity results indicated that patient's hippocampus recruited alternate pathways and regions to guide and help them complete the wayfinding task. Structural and functional differences in the hippocampus might explain the connectivity differences and CB deficit in schizophrenia.

A two-step process for synthesizing 2H-1-benzopyrans from phenols and β-halopropionaldehyde acetals is detailed.

An association between affective disorders and alterations in glucose utilization has been recognized. The authors administered a 5-hour oral glucose tolerance test (GTT) to 28 depressed patients and 21 healthy volunteer control subjects and measured serum glucose as well as plasma insulin and glucagon responses. Depressed patients demonstrated significantly higher basal glucose levels, greater cumulative glucose responses after the GTT, and larger cumulative insulin responses after the GTT than control subjects. Values for cumulative glucagon did not significantly differ between groups. These findings indicate the presence of a functional state of insulin resistance during major depressive illness and suggest the presence of a more generalized biological disturbance in some depressed patients.