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Psychiatry Research Nov 2020Individual negative symptoms have rarely been examined with regard to their relationship with suicide in schizophrenia, which continues to affect up to 13% of people...
Individual negative symptoms have rarely been examined with regard to their relationship with suicide in schizophrenia, which continues to affect up to 13% of people with the disorder. Symptoms such as blunted affect, which can be an enduring hallmark of schizophrenia, may impact suicide through increasing isolation, leading to poor functional recovery and diminished quality of life. A systematic review following PRISMA guidelines and pre-registered on PROSPERO (CRD4219143373) was conducted; EMBASE, PsychInfo, and MedLine were searched until January 2020. Eight hundred and fifty-six articles were identified from the databases and 2 papers were identified from other resources. Twelve papers met inclusion criteria for the review. Nine out of twelve papers report a positive direct or indirect association between blunted affect and suicide in schizophrenia and three papers showed no association. The majority of included studies suggest that blunted affect may be indirectly related to suicide through risk factors such as emotional withdrawal, depressive symptoms, hopelessness, low self-esteem and negative evaluation. Future studies should include assessment of blunted affect as a potential mediator in the generation of suicidal behaviour in patients with such factors.
Topics: Adult; Affect; Cross-Sectional Studies; Humans; Quality of Life; Risk Factors; Schizophrenia; Schizophrenic Psychology; Suicidal Ideation; Suicide
PubMed: 32798929
DOI: 10.1016/j.psychres.2020.113355 -
Nature Oct 2022Recent studies suggested that microglia, the primary brain immune cells, can affect circuit connectivity and neuronal function. Microglia infiltrate the neuroepithelium...
Recent studies suggested that microglia, the primary brain immune cells, can affect circuit connectivity and neuronal function. Microglia infiltrate the neuroepithelium early in embryonic development and are maintained in the brain throughout adulthood. Several maternal environmental factors-such as an aberrant microbiome, immune activation and poor nutrition-can influence prenatal brain development. Nevertheless, it is unknown how changes in the prenatal environment instruct the developmental trajectory of infiltrating microglia, which in turn affect brain development and function. Here we show that, after maternal immune activation (MIA) in mice, microglia from the offspring have a long-lived decrease in immune reactivity (blunting) across the developmental trajectory. The blunted immune response was accompanied by changes in chromatin accessibility and reduced transcription factor occupancy of the open chromatin. Single-cell RNA-sequencing analysis revealed that MIA does not induce a distinct subpopulation but, rather, decreases the contribution to inflammatory microglia states. Prenatal replacement of microglia from MIA offspring with physiological infiltration of naive microglia ameliorated the immune blunting and restored a decrease in presynaptic vesicle release probability onto dopamine receptor type-two medium spiny neurons, indicating that aberrantly formed microglia due to an adverse prenatal environment affect the long-term microglia reactivity and proper striatal circuit development.
Topics: Animals; Chromatin; Female; Inflammation; Mice; Microglia; Mothers; Neostriatum; Neural Pathways; Neurons; Pregnancy; Prenatal Exposure Delayed Effects; RNA-Seq; Receptors, Dopamine; Single-Cell Analysis; Transcription Factors
PubMed: 36171283
DOI: 10.1038/s41586-022-05274-z -
Schizophrenia Research Nov 2014Deficits in nonverbal vocal expression (e.g., blunted vocal affect, alogia) are a hallmark of schizophrenia and are a focus of the Research Domain Criteria initiative... (Meta-Analysis)
Meta-Analysis Review
Deficits in nonverbal vocal expression (e.g., blunted vocal affect, alogia) are a hallmark of schizophrenia and are a focus of the Research Domain Criteria initiative from the National Institute of Mental Health. Results from studies using symptom rating scales suggest that these deficits are profound; on the order of four to six standard deviations. To complement this endeavor, we conducted a meta-analysis of studies employing objective analysis of natural speech in patients with schizophrenia and nonpsychiatric controls. Thirteen studies, collectively including 480 patients with schizophrenia and 326 nonpsychiatric controls, were identified. There was considerable variability across studies in which aspects of vocal communication were examined and in the magnitudes of deficit. Overall, speech production (reflecting alogia) was impaired at a large effects size level (d=-.80; k=13), whereas speech variability (reflecting blunted affect) was much more modest (d=-.36; k=2). Regarding the former, this was largely driven by measures of pause behavior, as opposed to other aspects of speech (e.g., number of words/utterances). On the other hand, ratings of negative symptoms across these studies suggested profound group differences (d=3.54; k=4). These data suggest that only certain aspects of vocal expression are affected in schizophrenia, and highlight major discrepancies between symptom rating and objective-based measures. The discussion centers on advancing objective analysis for understanding vocal expression in schizophrenia and for identifying and defining more homogenous patient subsets for study.
Topics: Affective Symptoms; Aphasia; Humans; Schizophrenia; Speech Production Measurement
PubMed: 25261880
DOI: 10.1016/j.schres.2014.09.013 -
PloS One 2015Blunted affect, also referred to as emotional blunting, is a prominent symptom of schizophrenia. Patients with blunted affect have difficulty in expressing their... (Meta-Analysis)
Meta-Analysis
Blunted affect, also referred to as emotional blunting, is a prominent symptom of schizophrenia. Patients with blunted affect have difficulty in expressing their emotions. The work of Abrams and Taylor and their development of the Rating Scale for Emotional Blunting in the late 1970's was an early indicator that blunted affect could indeed be assessed reliably. Since then, several new instruments assessing negative symptoms with subscales measuring blunted affect have been developed. In light of this, we aim to provide researchers and clinicians with a systematic review of the different instruments used to assess blunted affect by providing a comparison of the type, characteristics, administration and psychometric properties of these instruments. Studies reporting on the psychometric properties of instruments assessing blunted affect in patients with schizophrenia were included. Reviews and case studies were excluded. We reviewed 30 full-text articles and included 15 articles and 10 instruments in this systematic review. On average the instruments take 15-30 minutes to administer. We found that blunted affect items common across all instruments assess: gestures, facial expressions and vocal expressions. The CAINS Self-report Expression Subscale, had a low internal consistency score. This suggests that this sub-scale does not reliably assess patients' self-reported blunted affect symptoms and is likely due to the nature of blunted affect. Instruments correlated minimally with instruments measuring positive symptoms and more importantly with depression suggesting that the instruments distinguish between seemingly similar symptoms.
Topics: Depression; Facial Expression; Humans; Psychiatric Status Rating Scales; Psychometrics; Reproducibility of Results; Schizophrenia; Schizophrenic Psychology; Self Report
PubMed: 26035179
DOI: 10.1371/journal.pone.0127740 -
Journal of Psychiatric Research Jun 2022Clinical interviews and laboratory-based emotional induction paradigms provide consistent evidence that facial affect is blunted in many individuals with schizophrenia....
Clinical interviews and laboratory-based emotional induction paradigms provide consistent evidence that facial affect is blunted in many individuals with schizophrenia. Although it is clear that blunted facial affect is not a by-product of diminished emotional experience in schizophrenia, factors contributing to blunted affect remain unclear. The current study used a combination of ambulatory video recordings that were evaluated via computerized facial affect analysis and concurrently completed ecological momentary assessment surveys to assess whether blunted affect reflects insufficient reactivity to affective or contextual factors. Specifically, whether individuals with schizophrenia require more intense affective experiences to produce expression, or whether they are less reactive to social factors (i.e. being in the presence of others, social motivation). Participants included outpatients with schizophrenia (n = 33) and healthy controls (n = 31) who completed six days of study procedures. Multilevel linear models were evaluated using both Null-Hypothesis Statistical Testing and Bayesian analyses. Individuals with schizophrenia displayed comparable expression of positive and negative emotion to controls during daily life, and no evidence was found for a different intensity of experience required for expression in either group. However, social factors differentially influenced facial expression in schizophrenia compared to controls, such that individuals with schizophrenia did not modulate their expressions based on social motivation to the same extent as controls. These findings suggest that social motivation may play an important role in determining when blunting occurs.
Topics: Bayes Theorem; Emotions; Facial Expression; Humans; Schizophrenia; Social Factors; Video Recording
PubMed: 35366600
DOI: 10.1016/j.jpsychires.2022.03.024 -
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 -
Brain : a Journal of Neurology Apr 1998Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very...
Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.
Topics: Adult; Affect; Aged; Attention; Brain; Cerebellar Diseases; Cerebellar Neoplasms; Cerebral Infarction; Cerebrovascular Disorders; Cognition; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurologic Examination; Neuropsychological Tests; Syndrome
PubMed: 9577385
DOI: 10.1093/brain/121.4.561 -
The Journal of Neuroscience : the... Oct 2022Humans routinely learn the value of actions by updating their expectations based on past outcomes - a process driven by reward prediction errors (RPEs). Importantly,...
Humans routinely learn the value of actions by updating their expectations based on past outcomes - a process driven by reward prediction errors (RPEs). Importantly, however, implementing a course of action also requires the investment of effort. Recent work has revealed a close link between the neural signals involved in effort exertion and those underpinning reward-based learning, but the behavioral relationship between these two functions remains unclear. Across two experiments, we tested healthy male and female human participants ( = 140) on a reinforcement learning task in which they registered their responses by applying physical force to a pair of hand-held dynamometers. We examined the effect of effort on learning by systematically manipulating the amount of force required to register a response during the task. Our key finding, replicated across both experiments, was that greater effort increased learning rates following positive outcomes and decreased them following negative outcomes, which corresponded to a differential effect of effort in boosting positive RPEs and blunting negative RPEs. Interestingly, this effect was most pronounced in individuals who were more averse to effort in the first place, raising the possibility that the investment of effort may have an adaptive effect on learning in those less motivated to exert it. By integrating principles of reinforcement learning with neuroeconomic approaches to value-based decision-making, we show that the very act of investing effort modulates one's capacity to learn, and demonstrate how these functions may operate within a common computational framework. Recent work suggests that learning and effort may share common neurophysiological substrates. This raises the possibility that the very act of investing effort influences learning. Here, we tested whether effort modulates teaching signals in a reinforcement learning paradigm. Our results showed that effort resulted in more efficient learning from positive outcomes and less efficient learning from negative outcomes. Interestingly, this effect varied across individuals, and was more pronounced in those who were more averse to investing effort in the first place. These data highlight the importance of motivational factors in a common framework of reward-based learning, which integrates the computational principles of reinforcement learning with those of value-based decision-making.
Topics: Humans; Male; Female; Decision Making; Reinforcement, Psychology; Reward; Motivation; Affect
PubMed: 36096671
DOI: 10.1523/JNEUROSCI.2223-21.2022 -
Schizophrenia Research Jun 2020Negative symptoms reflect one of the most debilitating aspects of one of the most debilitating diseases known to humankind. As yet, our treatments for negative symptoms...
Negative symptoms reflect one of the most debilitating aspects of one of the most debilitating diseases known to humankind. As yet, our treatments for negative symptoms are palliative at best and our understanding of their causes is relatively superficial. To address this, we are developing objective ambulatory tools for digitally phenotyping their severity which can be used outside the confines of the traditional clinical and research settings. The present study evaluated the feasibility, reliability and validity of ambulatory vocal acoustic and facial emotion expression analysis. Videos were provided by 25 patients with schizophrenia or schizoaffective disorder and 27 nonpsychiatric controls using inexpensive, non-invasive ambulatory recording methods. Controls provided 411 video recordings, and patients provided 377 video recordings; an average of 15.22 and 14.50 per participant per group respectively. The vast majority (over 80%) of these videos were usable for analysis. An empirically-supported, limited-feature vocal (7 features) and facial (3 features) set was examined. Within participants, these features varied considerably over time, but showed moderate to good test-retest reliability in many cases once contextual factors (e.g., activity involved in at the time of testing) were accounted for. Vocal and facial features showed statistically significant convergence with a "gold standard" negative symptom measure. Ambulatory vocal/facial features were more strongly associated with engagement in social or work activities in patients than negative symptom ratings. These data support the use of ambulatory vocal/facial analytic technologies for digital phenotyping of these negative symptoms.
Topics: Affect; Aphasia; Facial Expression; Humans; Psychotic Disorders; Reproducibility of Results; Schizophrenia
PubMed: 32247747
DOI: 10.1016/j.schres.2020.03.043