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Nature Reviews. Endocrinology Aug 2019Exercise is the elixir of health. However, timing can boost or blunt exercise performance and health benefits. Two complementary studies used transcriptomic and...
Exercise is the elixir of health. However, timing can boost or blunt exercise performance and health benefits. Two complementary studies used transcriptomic and metabolomic tools to dissect how time of day affects the impact of exercise. The findings open new avenues for optimizing timing of physical activity to boost its benefits further.
Topics: Exercise; Exercise Tolerance; Humans
PubMed: 31217576
DOI: 10.1038/s41574-019-0229-z -
Neuropharmacology May 2021Blunted stress reactivity resulting from early exposure to stress during childhood and adolescence may increase vulnerability to addiction. Early life adversity (ELA)... (Review)
Review
Blunted stress reactivity resulting from early exposure to stress during childhood and adolescence may increase vulnerability to addiction. Early life adversity (ELA) affects brain structure and function and results in blunted stress axis reactivity. In this review, we focus on the underlying neurobiological mechanisms associated with a blunted response to stress, ELA, and risk for addictive disorders. ELA and blunted reactivity are accompanied by unstable mood regulation, impulsive behaviors, and reduced cognitive function. Neuroimaging studies reveal cortical and subcortical changes in persons exposed to ELA and those who have a genetic disposition for addiction. We propose a model in which blunted stress reactivity may be a marker of risk for addiction through an altered motivational and behavioral reactivity to stress that contribute to disinhibited behavioral reactivity and impulsivity leading in turn to increased vulnerability for substance use. Evidence supporting this hypothesis in the context of substance use initiation, maintenance, and risk for relapse is presented. The effects of ELA on persons at risk for addiction may lead to early experimentation with drugs of abuse. Early adoption of drug intake may alter neuroregulation in such vulnerable persons leading to a permanent dysregulation of motivational responses consistent with dependence. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.
Topics: Adaptation, Psychological; Adolescent; Adverse Childhood Experiences; Behavior, Addictive; Child; Cognition; Humans; Impulsive Behavior; Stress, Psychological; Substance-Related Disorders
PubMed: 33711348
DOI: 10.1016/j.neuropharm.2021.108519 -
Schizophrenia Research Mar 2022Blunted facial affect is a transdiagnostic component of Serious Mental Illness (SMI) and is associated with a host of negative outcomes. However, blunted facial affect...
Blunted facial affect is a transdiagnostic component of Serious Mental Illness (SMI) and is associated with a host of negative outcomes. However, blunted facial affect is a poorly understood phenomenon, with no known cures or treatments. A critical step in better understanding its phenotypic expression involves clarifying which facial expressions are altered in specific ways and under what contexts. The current literature suggests that individuals with SMI show decreased positive facial expressions, but typical, or even increased negative facial expressions during laboratory tasks. While this literature has coalesced around general trends, significantly more nuance is available regarding what components facial expressions are atypical and how those components are associated with increased severity of clinical ratings. The present project leveraged computerized facial analysis to test whether clinician-rated blunted affect is driven by decreases in duration, intensity, or frequency of positive versus other facial expressions during a structured clinical interview. Stable outpatients meeting criteria for SMI (N = 59) were examined. Facial expression did not generally vary as a function of clinical diagnosis. Overall, clinically-rated blunted affect was not associated with positive expressions, but was associated with decreased surprise and increased anger, sadness, and fear expressions. Blunted affect is not a monolithic lack of expressivity, and increased precision in operationally defining it is critical for uncovering its causes and maintaining factors. Our discussion focuses on this effort, and on advancing digital phenotyping of blunted facial affect more generally.
Topics: Anger; Emotions; Facial Expression; Humans; Mental Disorders
PubMed: 35074531
DOI: 10.1016/j.schres.2021.12.026 -
Cellular and Molecular Life Sciences :... Aug 2021Cancer cachexia afflicts many advanced cancer patients with many progressing to death. While there have been many advancements in understanding the molecular mechanisms... (Review)
Review
Cancer cachexia afflicts many advanced cancer patients with many progressing to death. While there have been many advancements in understanding the molecular mechanisms that contribute to the development of cancer cachexia, substantial gaps still exist. Chemotherapy drugs often target ribosome biogenesis to slow or blunt tumor cell growth and proliferation. Some of the most frequent side-effects of chemotherapy are loss of skeletal muscle mass, muscular strength and an increase in fatigue. Given that ribosome biogenesis has emerged as a main mechanism regulating muscle hypertrophy, and more recently, also implicated in muscle atrophy, we propose that some chemotherapy drugs can cause further muscle wasting via its effect on skeletal muscle cells. Many chemotherapy drugs, including the most prescribed drugs such as doxorubicin and cisplatin, affect ribosomal DNA transcription, or other pathways related to ribosome biogenesis. Furthermore, middle-aged and older individuals are the most affected population with cancer, and advanced cancer patients often show reduced levels of physical inactivity. Thus, aging and inactivity can themselves affect muscle ribosome biogenesis, which can further worsen the effect of chemotherapy on skeletal muscle ribosome biogenesis and, ultimately, muscle mass and function. We propose that chemotherapy can accelerate the onset or worsen cancer cachexia via its inhibitory effects on skeletal muscle ribosome biogenesis. We end our review by providing recommendations that could be used to ameliorate the negative effects of chemotherapy on skeletal muscle ribosome biogenesis.
Topics: Aging; Animals; Antineoplastic Agents; Cachexia; Humans; Muscle, Skeletal; Neoplasms; Organelle Biogenesis; Ribosomes
PubMed: 34196731
DOI: 10.1007/s00018-021-03888-6 -
Frontiers in Behavioral Neuroscience 2018The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how... (Review)
Review
The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how both direct and indirect manipulations of the LC-NE system affect cued and contextual aversive learning and memory. We propose that NE dynamically modulates Pavlovian conditioning and extinction, either promoting or impairing learning aversive processes under different levels of behavioral arousal. We suggest that under high levels of stress (e.g., during/soon after fear conditioning) the locus coeruleus (LC) promotes cued fear learning by enhancing amygdala function while simultaneously blunting prefrontal function. Under low levels of arousal, the LC promotes PFC function to promote downstream inhibition of the amygdala and foster the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex (mPFC) might be described by an inverted-U function such that it can either enhance or hinder learning depending on arousal states. In addition, LC-NE seems to be particularly important for the acquisition, consolidation and extinction of contextual fear memories. This may be due to dense adrenoceptor expression in the hippocampus (HPC) which encodes contextual information, and the ability of NE to regulate long-term potentiation (LTP). Moreover, recent work reveals that the diversity of LC-NE functions in aversive learning and memory are mediated by functionally heterogeneous populations of LC neurons that are defined by their projection targets. Hence, LC-NE function in learning and memory is determined by projection-specific neuromodulation that accompanies various states of behavioral arousal.
PubMed: 29593511
DOI: 10.3389/fnbeh.2018.00043 -
Conflict and Health Jan 2024The United Nations estimate a quarter of the global population currently lives in violent conflict zones. Radiology is an integral part of any healthcare system,... (Review)
Review
The United Nations estimate a quarter of the global population currently lives in violent conflict zones. Radiology is an integral part of any healthcare system, providing vital information to aid diagnosis and treatment of a range of disease and injury. However, its delivery in conflict-affected settings remains unclear. This study aims to understand how radiology services are currently delivered in conflict settings, the challenges of doing so, and potential solutions. A hermeneutic narrative review of multiple databases, including grey literature sources, was undertaken. Key themes were identified, and articles grouped accordingly. Various conflict zones including Gaza, Ukraine, Iraq, Yemen, Afghanistan, and Somalia were identified in literature relating to radiology services. Three key themes were identified: underserving of local medical imaging services, strong presence of military hospitals, and the importance of teleradiology. A severe shortage of radiologists, technicians, and equipment in conflict affected settings are a significant cause of the underserving by local services. Teleradiology has been used to blunt the acuity of the these struggling services, alongside military hospitals which often serve local populations. Radiology faces unique challenges compared to other healthcare services owing to its expensive equipment which is difficult to fund and can be less effective due to international sanctions placed on contrast medium to enhance image quality. Further the equipment is reliant on local infrastructure, e.g., power supply, which can be affected in conflict. Key recommendations to improve radiology services include retention of radiologists within conflict zones, careful allocation of funds to supply necessary imaging machinery, international cooperation to ensure sanctions do not affect sourcing of radiology equipment, special training for military medical teams to help preparedness for the unique demands of the local population, and investment in communication devices, like smartphones, to allow international teleradiology efforts.
PubMed: 38238758
DOI: 10.1186/s13031-023-00550-9 -
Frontiers in Psychiatry 2022Autoantibody-mediated psychiatric disorder is often difficult to diagnose as the clinical features of psychiatric disorder associated with neural autoantibodies are...
BACKGROUND
Autoantibody-mediated psychiatric disorder is often difficult to diagnose as the clinical features of psychiatric disorder associated with neural autoantibodies are often similar. Thus, it is of major relevance to investigate whether psychopathology can differentiate between both disease entities as a biomarker and help us in searching for specific autoantibodies associated with psychiatric symptoms.
METHODS
We enrolled 154 patients of the Department of Psychiatry and Psychotherapy of the University Medical Center Göttingen with psychopathology data and retrospectively evaluated their patient records using the classification systems AMDP (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie) and HiTOP (Hierarchical Taxonomy of Psychopathology).
RESULTS
We identified 35 psychiatric patients revealing autoantibodies in their serum and/or cerebrospinal fluid (CSF) and 119 with no autoantibodies. Relying on the AMDP system, many more psychiatric patients with serum autoantibodies (51%) had problems with orientation than those without autoantibodies (32%) ( < 0.05). Furthermore, fewer psychiatric patients with serum autoantibodies exhibited a blunted affect (11.4 vs. 32.8%, < 0.01) and affective rigidity (20 vs. 45%, < 0.01). In particular, psychiatric patients presenting CSF autoantibodies (indicating an autoimmune symptomatic basis) experience more loss of vitality (5%) than those without autoantibodies (0%) ( < 0.05). Another interesting finding is that according to the AMDP classification, a manic syndrome is much more frequent in autoantibody-positive (8.6%) than autoantibody-negative psychiatric patients (0.8%) ( < 0.05). Another aspect is the more frequent occurrence of attention and memory deficits in patients with autoantibodies against intracellular targets compared with targets on the membrane surface.
CONCLUSION
Our findings indicate that neural autoantibodies in psychiatric patients could indicate a phenotype more often characterized by a manic syndrome, orientation disturbances within the cognitive spectrum, and fewer affect disturbances characterized by less blunted affect and not as seriously impaired feelings of vitality compared to controls. The novelty of our approach is the extensive autoantibody tests for various psychiatric syndromes in combination with a profound psychometric measurement with two different scales.
PubMed: 36440415
DOI: 10.3389/fpsyt.2022.945549 -
Journal of Psychiatric Research Mar 2021Affect dynamics reflect individual differences in how emotional information is processed, and may provide insights into how depressive episodes develop. To extend prior...
Affect dynamics reflect individual differences in how emotional information is processed, and may provide insights into how depressive episodes develop. To extend prior studies that examined affect dynamics in currently depressed individuals, the present study tested in 68 non-depressed young adults whether three well-established risk factors for major depressive disorder (MDD) - (a) past episodes of MDD, (b) family history of MDD, and (c) reduced neurophysiological responses to reward - predicted mean levels, instability, or inertia (i.e., inflexibility) of positive affect (PA) and/or negative affect (NA). Momentary PA and NA were assessed up to 6 times per day for 14 days (mean number of surveys completed = 45.89). MDD history and family history of MDD were assessed via semi-structured interview, and neurophysiological responses to reward were indexed using the Reward Positivity, an event-related potential related to depression. After adjusting for current depressive symptoms, results indicated that (a) past episodes of MDD predicted higher mean levels of NA, (b) family history of MDD predicted greater PA inertia, and (c) blunted reactivity to reward predicted greater NA inertia. Collectively, these results suggest that elevated mean levels of NA and inflexibility of PA and NA may be potential mechanisms that confer risk for depression.
Topics: Affect; Depression; Depressive Disorder, Major; Ecological Momentary Assessment; Humans; Risk Factors; Young Adult
PubMed: 33450467
DOI: 10.1016/j.jpsychires.2021.01.007