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Annual Review of Physiology Feb 2020A progressive decline in maximum heart rate (mHR) is a fundamental aspect of aging in humans and other mammals. This decrease in mHR is independent of gender, fitness,... (Review)
Review
A progressive decline in maximum heart rate (mHR) is a fundamental aspect of aging in humans and other mammals. This decrease in mHR is independent of gender, fitness, and lifestyle, affecting in equal measure women and men, athletes and couch potatoes, spinach eaters and fast food enthusiasts. Importantly, the decline in mHR is the major determinant of the age-dependent decline in aerobic capacity that ultimately limits functional independence for many older individuals. The gradual reduction in mHR with age reflects a slowing of the intrinsic pacemaker activity of the sinoatrial node of the heart, which results from electrical remodeling of individual pacemaker cells along with structural remodeling and a blunted β-adrenergic response. In this review, we summarize current evidence about the tissue, cellular, and molecular mechanisms that underlie the reduction in pacemaker activity with age and highlight key areas for future work.
Topics: Aging; Animals; Biological Clocks; Female; Heart; Heart Rate; Humans; Male; Sinoatrial Node
PubMed: 31756134
DOI: 10.1146/annurev-physiol-021119-034453 -
European Journal of Translational... Mar 2022Neuromuscular disorders are a heterogeneous group of acquired or hereditary conditions that affect striated muscle function. The resulting decrease in muscle strength...
Neuromuscular disorders are a heterogeneous group of acquired or hereditary conditions that affect striated muscle function. The resulting decrease in muscle strength and motility irreversibly impacts quality of life. In addition to directly affecting skeletal muscle, pathogenesis can also arise from dysfunctional crosstalk between nerves and muscles, and may include cardiac impairment. Muscular weakness is often progressive and paralleled by continuous decline in the ability of skeletal muscle to functionally adapt and regenerate. Normally, the skeletal muscle resident stem cells, named satellite cells, ensure tissue homeostasis by providing myoblasts for growth, maintenance, repair and regeneration. We recently defined 'Satellite Cell-opathies' as those inherited neuromuscular conditions presenting satellite cell dysfunction in muscular dystrophies and myopathies (doi:10.1016/j.yexcr.2021.112906). Here, we expand the portfolio of Satellite Cell-opathies by evaluating the potential impairment of satellite cell function across all 16 categories of neuromuscular disorders, including those with mainly neurogenic and cardiac involvement. We explore the expression dynamics of myopathogenes, genes whose mutation leads to skeletal muscle pathogenesis, using transcriptomic analysis. This revealed that 45% of myopathogenes are differentially expressed during early satellite cell activation (0 - 5 hours). Of these 271 myopathogenes, 83 respond to Pax7, a master regulator of satellite cells. Our analysis suggests possible perturbation of satellite cell function in many neuromuscular disorders across all categories, including those where skeletal muscle pathology is not predominant. This characterisation further aids understanding of pathomechanisms and informs on development of prognostic and diagnostic tools, and ultimately, new therapeutics.
PubMed: 35302338
DOI: 10.4081/ejtm.2022.10064 -
Cannabis and Cannabinoid Research Aug 2022The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB... (Meta-Analysis)
Meta-Analysis
The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB signaling, and disruptions in eCB signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity. Pharmacological and nonpharmacological behavioral interventions (e.g., exercise) that target the eCB system may be promising therapeutic approaches for the prevention and treatment of stress-related diseases. In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating eCB concentrations. We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on eCBs in humans and animal models. A total of 262 articles were screened for initial inclusion. Thirty-three articles (reporting on 57 samples) were included in the systematic review and 10 were included in the meta-analysis. The majority of samples that measured anandamide (AEA) showed a significant increase in AEA concentrations following acute exercise (74.4%), whereas effects on 2-arachidonoylglycerol (2-AG) were inconsistent. The meta-analysis, however, revealed a consistent increase in both AEA and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression). There was substantial heterogeneity in the magnitude of the effect across studies, which may relate to exercise intensity, physical fitness, timing of measurement, and/or fasted state. Effects of chronic exercise were inconsistent. Potential interpretations and implications of exercise-induced mobilization of eCBs are discussed, including refilling of energy stores and mediating analgesic and mood elevating effects of exercise. We also offer recommendations for future work and discuss therapeutic implications for exercise in the prevention and treatment of stress-related psychopathology.
Topics: Affect; Animals; Anxiety; Endocannabinoids; Humans; Mice; Running; Stress Disorders, Post-Traumatic
PubMed: 34870469
DOI: 10.1089/can.2021.0113 -
Neuroscience and Biobehavioral Reviews Jan 2023Research on negative symptoms of schizophrenia has received renewed interest since the 1980s. A scientometric analysis that objectively maps scientific knowledge, with... (Review)
Review
Research on negative symptoms of schizophrenia has received renewed interest since the 1980s. A scientometric analysis that objectively maps scientific knowledge, with changes in recent trends, is currently lacking. We searched the Web of Science Core Collection (WOSCC) on December 17, 2021 using relevant keywords. R-bibliometrix and CiteSpace were used to perform the analysis. We retrieved 27,568 references published between 1966 and 2022. An exponential rise in scientific interest was observed, with an average annual growth rate in publications of 16.56% from 1990 to 2010. The co-cited reference network that was retrieved presented 24 different clusters with a well-structured network (Q=0.7921; S=0.9016). Two distinct major research trends were identified: research on the conceptualization and treatment of negative symptoms. The latest trends in research on negative symptoms include evidence synthesis, nonpharmacological treatments, and computational psychiatry. Scientometric analyses provide a useful summary of changes in negative symptom research across time by identifying intellectual turning point papers and emerging trends. These results will be informative for systematic reviews, meta-analyses, and generating novel hypotheses.
Topics: Humans; Concept Formation; Psychiatry; Schizophrenia; Systematic Reviews as Topic
PubMed: 36463972
DOI: 10.1016/j.neubiorev.2022.104979 -
Journal of Affective Disorders Mar 2021Inadequate treatment response and emotional blunting are common challenges with selective serotonin reuptake inhibitors/serotonin-noradrenaline reuptake inhibitors...
INTRODUCTION
Inadequate treatment response and emotional blunting are common challenges with selective serotonin reuptake inhibitors/serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) for major depressive disorder (MDD). We investigated the effectiveness of vortioxetine on emotional blunting in patients with partial response to treatment with SSRIs/SNRIs.
METHODS
Patients with MDD who experienced a partial response to SSRI/SNRI monotherapy at adequate dose for ≥6 weeks were switched to 8 weeks of vortioxetine treatment 10-20 mg/day (Study NCT03835715). Key inclusion criteria were Montgomery-Åsberg Depression Rating Scale (MADRS) total score >21 and <29, current major depressive episode <12 months, Oxford Depression Questionnaire (ODQ) total score ≥50, and confirmation of emotional blunting by standardized screening question. Emotional blunting was assessed by ODQ and depressive symptoms by MADRS. Other outcomes assessed included motivation and energy (Motivation and Energy Inventory [MEI]), cognitive performance (Digit Symbol Substitution Test [DSST]), and overall functioning (Sheehan Disability Scale [SDS]).
RESULTS
At week 8, patients (N=143) had improved by -29.8 points (p<0.0001) in ODQ total score; 50% reported no emotional blunting in response to standardized screening question. Significant improvements were observed on the DSST, MEI, and SDS at all time points assessed, and 47% of patients were in remission (MADRS total score ≤10) at week 8. The most common treatment-emergent adverse events included nausea, headache, dizziness, vomiting, and diarrhea.
LIMITATIONS
No prospective phase before medication switch.
CONCLUSION
Vortioxetine 10-20 mg effectively improved emotional blunting, overall functioning, motivation and energy, cognitive performance, and depressive symptoms in patients with MDD with partial response to SSRI/SNRI therapy and emotional blunting.
Topics: Depressive Disorder, Major; Double-Blind Method; Humans; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Treatment Outcome; Vortioxetine
PubMed: 33516560
DOI: 10.1016/j.jad.2020.11.106