When Did the Empathy Die?: Examining the Correlation Between Length of Medical Training and Level of Empathy.

Purpose: Empathy is an important skill for physicians as it can lead to improved patient outcomes and satisfaction. This study assessed self-reported empathy by medical students across all four years of medical school and potential differences in empathy across students interested in different subspecialties. Method: All medical students enrolled at New York Medical College in August 2020 were invited to participate in this study. Participants completed the student version of the Jefferson Scale of Empathy. Results: A total of 179 medical students participated. Mean empathy score in fourth-year students was significantly lower than that in first-year students. Mean empathy score was greatest among students interested in Pediatrics and was greater in participants who identified as women. Conclusions: Self-reported empathy may be lower in upper-year medical students when compared to lower-year students. The potential reasons for lower empathy in the later years of training are discussed. A systematic curriculum for teaching and maintaining empathy should be developed and uniformly implemented across medical schools to combat a potential decline in empathy.

A meta-analysis of the potential antidepressant effects of buprenorphine versus placebo as an adjunctive pharmacotherapy for treatment-resistant depression.

BACKGROUND: Numerous reports have suggested that buprenorphine may have antidepressant effects. Many individuals with depressive disorders don't respond to first-line treatment and are classified with treatment-resistant depression (TRD). Novel therapies for depression are required to better treat this population. This meta-analysis of randomized placebo-controlled trials sought to evaluate the potential antidepressant effects of buprenorphine as an adjunctive pharmacological treatment for individuals with TRD. METHODS: PubMed, Embase, CINAHL, Web of Science, and ClinicalTrials.gov databases were searched until June 2019 for original peer-reviewed reports of buprenorphine used for the treatment of depression. Standardized mean differences (SMD) were generated from random effects models. Risk of publication bias was assessed using a funnel plot. Potential sources of heterogeneity were explored in subgroup analyses. RESULTS: In six studies that met inclusion criteria, depression symptom severity in individuals with TRD was not significantly decreased after an adjunctive intervention with buprenorphine when compared to placebo (SMD = -0.07, 95% CI: -0.21-0.06, p = 0.30). Five of the six studies utilized a combination of buprenorphine/samidorphan. In these studies, depression symptom severity was also not significantly reduced after intervention compared to placebo (SMD = -0.08, 95% CI: -0.21 - 0.05, p = 0.23). LIMITATIONS: Five included studies were performed by the same research group with significant conflicts of interest. CONCLUSIONS: This meta-analysis did not reveal a significant reduction in depression symptom severity in individuals with TRD after an adjunctive intervention with buprenorphine when compared to placebo. However, more optimal doses of buprenorphine (2 mg/day) and longer treatment lengths should be explored.

Association Between Sphingolipids and Cardiopulmonary Fitness in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation.

The long-term benefits conferred by cardiac rehabilitation (CR) in those with coronary artery disease (CAD) are strongly linked with an improvement in cardiopulmonary fitness. This study aimed to determine the association between peripheral sphingolipids and cardiopulmonary fitness in CAD subjects undertaking CR. Patients with CAD (n = 100, mean age = 64 ± 6 years, 85% male, mean years of education = 17 ± 3 years) underwent 6 months of CR with blood collected at baseline, 3 and 6 months. Cardiopulmonary fitness was assessed by measuring peak oxygen uptake (VO2peak) at all time points. High performance liquid chromatography coupled electrospray ionization tandem mass spectrometry was used to quantify plasma sphingolipid concentrations. Cross-sectional and longitudinal associations between sphingolipids and VO2peak were assessed using linear regressions and mixed models, respectively. Higher concentrations of sphingomyelin C18:1 (ß = -0.26, p = .01), ceramides C16:0 (ß = -0.24, p = .02), C18:0 (ß = -0.29, p = .002), C20:0 (ß = -0.24, p = .02) and C24:1 (ß = -0.24, p = .01) and monohexylceramide C18:0 (ß = -0.23, p = .02) were associated with poorer VO2peak at baseline. An improvement in VO2peak was associated with a decrease in sphingomyelin C18:1 (b = -10.09, p = .006), ceramides C16:0 (b = -9.25, p = .0003), C18:0 (b = -5.44, p = .0003) and C24:1 (b = -2.46, p = .006) and monohexylceramide C18:0 (b = -5.37, p = .005). Specific long chain sphingolipids may be useful markers of fitness and response to exercise in CAD.

Association Between Endothelial Function and Cognitive Performance in Patients With Coronary Artery Disease During Cardiac Rehabilitation.

OBJECTIVE: Subtle cognitive deficits indicating early neural risk are common in the clinical presentation of coronary artery disease (CAD). Although deterioration may be mitigated by exercise, cognitive response to exercise is heterogeneous. Vasculopathy including endothelial dysfunction is a hallmark of CAD and may play an important role in impairing neural adaptation to exercise. This study aimed to assess peripheral measurements of endothelial function as predictors of cognitive performance in CAD participants undertaking cardiac rehabilitation (CR). METHODS: CAD patients (N = 64) undergoing CR were recruited for this prospective observational study. Neuropsychological and endothelial function assessments were performed at baseline and after 3 months of CR. Z-scores for overall cognitive performance and specific cognitive domains (verbal and visuospatial memory, processing speed, and executive function) were calculated. Endothelial function was measured by the reactive hyperemia index (RHI) using peripheral arterial tonometry. Cross-sectional and longitudinal associations between RHI and overall cognition were assessed using linear regressions and mixed models, respectively. Domain-specific associations were also explored. RESULTS: Although lower RHI was not associated with overall cognition at baseline (b = 0.26, p = .10), an increased RHI was significantly associated with an improvement in overall cognition (b = 0.55, p = .030) over 3 months. Lower RHI was associated with poorer verbal memory (ß = 0.28, p = .027) at baseline and an increased RHI over 3 months was associated with an improvement in processing speed (b = 0.42, p = .033). CONCLUSIONS: RHI may be a clinically useful predictor of cognitive change and might provide insight into the etiology of cognitive dysfunction in patients with CAD.

The effect of exercise on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF) in major depressive disorder: A meta-analysis.

Exercise interventions have been shown to successfully improve depression in patients with major depressive disorder (MDD), but like other forms of antidepressant treatment, exercise is not effective in all patients and its mechanisms of action have not been fully elucidated. Brain-derived neurotrophic factor (BDNF), a key mediator of neurogenesis and neuronal survival, has been shown to be decreased in individuals with MDD. One potential mechanism by which exercise alleviates depression is through an increase in BDNF. In order to evaluate this hypothesis, we conducted a meta-analysis of studies that assessed the effects of a chronic (multi-week) exercise intervention on BDNF concentrations in MDD patients. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after a chronic exercise intervention in MDD patients. Standardized mean differences (SMDs) were generated from random effects models. Potential sources of heterogeneity were explored in meta-regression analyses. In six studies that met inclusion criteria, resting blood concentrations of BDNF were not significantly higher after a chronic exercise intervention (SMD = 0.43, 95% CI: -0.06-0.92, p = 0.09) in MDD patients. This meta-analysis did not find evidence that a chronic aerobic exercise intervention increases resting concentrations of BDNF in the blood of MDD patients; however, there is a lack of studies in this area making it difficult to reach a definitive conclusion. Future studies on this topic with larger sample sizes and longer durations are needed to draw more robust conclusions.

Plasma sphingolipids and depressive symptoms in coronary artery disease.

Background: Depression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects. Methods: Depressive symptoms were measured using the depression subscale of the self-reported Hospital Anxiety and Depression Scale (HADS). Sphingolipid concentrations were measured from fasting plasma samples using high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Linear regression models were used to assess associations between log-transformed concentrations of plasma sphingolipids and depressive symptoms. Results: A total of 111 CAD patients (mean (SD) age = 63.6 ± 6.4, 84.7% male) were included. In linear regression analyses, higher plasma concentrations of ceramides C16:0 (ß = 0.204, p = .026) and C18:0 (ß = 0.209, p = .023) and sphingomyelin SM18:1 (ß = 0.210, p = .024) were significantly associated with higher HADS depression subscale score after adjusting for covariates. Conclusion: Sphingolipids, in particular the ceramide species C16:0 and C18:0 and the sphingomyelin species SM18:1, may be implicated in the pathophysiology of depression in CAD. The association between plasma sphingolipid concentrations and depression should be further examined in CAD patients and in other populations.

A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise.

BACKGROUND: Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. OBJECTIVE: In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program. METHODS: Patients with CAD (n = 120, mean age = 64±6 y, 84% male, years of education = 16±3) underwent CR with neuropsychological assessments and blood collected at baseline, 3-, and 6-months. Z-scores based on age, gender, and education were combined for verbal memory, visuospatial memory, processing speed, executive function, and global cognition tasks to calculate cognitive domain Z-scores. Plasma sphingolipid concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Mixed models were used to identify sphingolipids significantly associated with performance in verbal memory and other cognitive domains, adjusting for potential confounders. RESULTS: A decrease in ceramide C18:0 concentration was significantly associated with improvement in verbal memory performance (b[SE] = -0.51 [0.25], p = 0.04), visuospatial memory (b[SE] = -0.44 [0.22], p = 0.05), processing speed (b[SE] = -0.89 [0.32], p = 0.007), and global cognition (b[SE] = -1.47 [0.59], p = 0.01) over 6 months of CR. CONCLUSIONS: Plasma ceramide C18:0 concentrations may be a sensitive marker of cognitive response to exercise in patients with CAD.

The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis.

It has been hypothesized that one mechanism through which physical activity provides benefits to cognition and mood is via increasing brain-derived neurotrophic factor (BDNF) concentrations. Some studies have reported immediate benefits to mood and various cognitive domains after a single session of exercise. This meta-analysis sought to determine the effect of a single exercise session on concentrations of BDNF in peripheral blood, in order to evaluate the potential role of BDNF in mediating the beneficial effects of exercise on brain health. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after acute exercise interventions. Risk of bias within studies was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using a funnel plot and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses. In 55 studies that met inclusion criteria, concentrations of peripheral blood BDNF were higher after exercise (SMD = 0.59, 95% CI: 0.46-0.72, P < 0.001). In meta-regression analysis, greater duration of exercise was associated with greater increases in BDNF. Subgroup analyses revealed an effect in males but not in females, and a greater BDNF increase in plasma than serum. Acute exercise increased BDNF concentrations in the peripheral blood of healthy adults. This effect was influenced by exercise duration and may be different across genders.

Ceramides and depression: A systematic review.

BACKGROUND: Major depressive disorder is a significant contributor to global disability and mortality. The mechanisms of depression are vast and not fully understood, and as a result current treatment of depression is suboptimal. Aberrant sphingolipid metabolism has been observed in some cases of depression, specifically alterations in ceramide concentrations. The role of ceramides and other sphingolipids in depression is a novel concept. This review summarizes and evaluates the current state of evidence for a role of ceramides in depression pathophysiology and the potential for novel depression pharmacotherapies targeting ceramide metabolism. METHODS: Medline, Embase, and PsycINFO databases were searched through October 2016 for English-language studies using combinations of the search terms: ceramide, depression, sphingolipid, and depressive symptoms. RESULTS: Of the 489 articles screened, 14 were included in the qualitative synthesis of this review article. Pre-clinical and clinical evidence suggest that ceramide species may contribute to depression pathophysiology. In human studies, ceramides C18:0 and C20:0 are the species most strongly linked to depression. Evidence for altered ceramide metabolism in depression is present, but data for a causal role of ceramides in depression are lacking. LIMITATIONS: This review was limited by potential reporting bias. Furthermore, a lack of specificity of which ceramides were altered in depression was common. CONCLUSIONS: Pharmacotherapy targeting ceramide metabolism may be a novel treatment option for depression. A number of pharmacological targets exists for ceramide reduction and a number of currently approved medications inhibit ceramide production. More evidence, pre-clinical and clinical, is warranted to determine the extent and consistency of the role of ceramides in depression.

The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis.

BACKGROUND: The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain-derived neurotrophic factor (BDNF) mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood. METHODS: MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions ≥ 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses. RESULTS: In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17-0.60, p < 0.001). Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33-0.99, p < 0.001) but not resistance training (SMD = 0.07, 95% CI: -0.15-0.30, p = 0.52) interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma. CONCLUSION: Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood.