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Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy.

Bioluminescence is a popular modality for imaging in living organisms. The platform relies on enzymatically (luciferase) generated light via the oxidation of small molecule luciferins. Since no external light is needed for photon production, there are no concerns with background autofluorescence or photobleaching over time-features that have historically limited other optical readouts. Bioluminescence is thus routinely used for longitudinal tracking across whole animals. Applications in the brain, though, have been more challenging due to a lack of sufficiently bioavailable, bright, and easily multiplexed probes. Recent years have seen the development of designer luciferase and luciferin pairs that address these issues, providing more sensitive and real-time readouts of biochemical features relevant to neurobiology. This review highlights many of the advances in bioluminescent probe design, with a focus on the small molecule light emitter, the luciferin. Specific efforts to improve luciferin pharmacokinetics and tissue-penetrant emission are covered, in addition to applications that such probes have enabled. The continued development of improved bioluminescent probes will aid in illuminating critical neurochemical processes in the brain.

Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.

Explanatory models of the mind inform our working assumptions about mental illness with direct implications for clinical practice. Neurobiological models assert that the mind can be understood in terms of genetics, chemistry, and neuronal circuits. Growing evidence suggests that clinical deployment of neurobiological models of illness may have unintended adverse effects on patient attitudes, public perception, provider empathy, and the effectiveness of psychiatric treatment. New approaches are needed to find a better language for describing (let alone explaining) the experience of mental illness. To address this gap, we draw upon interdisciplinary sources and semiotic theory to characterize the role of metaphor in the conceptualization and communication of psychopathology. We examine the metaphors recruited by contemporary neurobiological models and metaphors role in facilitating descriptive clarity or evocative creativity, depending on intention and context. These multiple roles reveal the implications of metaphorical reasoning in clinical practice, including cognitive flexibility, personalized communication, and uncertainty tolerance. With this analysis, we propose a clinical approach that embraces the meta-process of ongoing novel metaphor generation and co-elaboration, or languaging metaphors of psychopathology. Our goal is to bring attention to the value of employing ever-evolving, shapeable metaphorical depictions of psychiatric illness: metaphors that enable a capacity for change in individuals and society, reduce stigma, and nurture recovery.

Protein aggregation causes a wide range of neurodegenerative diseases. Targeting and removing aggregates, but not the functional protein, is a considerable therapeutic challenge. Here, we describe a therapeutic strategy called "RING-Bait," which employs an aggregating protein sequence combined with an E3 ubiquitin ligase. RING-Bait is recruited into aggregates, whereupon clustering dimerizes the RING domain and activates its E3 function, resulting in the degradation of the aggregate complex. We exemplify this concept by demonstrating the specific degradation of tau aggregates while sparing soluble tau. Unlike immunotherapy, RING-Bait is effective against both seeded and cell-autonomous aggregation. RING-Bait removed tau aggregates seeded from Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) brain extracts and was also effective in primary neurons. We used a brain-penetrant adeno-associated virus (AAV) to treat P301S tau transgenic mice, reducing tau pathology and improving motor function. A RING-Bait strategy could be applied to other neurodegenerative proteinopathies by replacing the Bait sequence to match the target aggregate. [Display omitted] • RING-Bait technology turns aggregate sequences into potent aggregate degraders • RING-Bait degraders remove pre-existing aggregates and prevent new ones from forming • RING-Bait degraders prevent seeded aggregation from human AD and PSP tau aggregates • RING-Bait degraders reduce tau pathology and improve motor function in vivo RING-Bait technology hijacks the process of templated aggregation to recruit ubiquitination machinery and selectively degrade pathogenic tau assemblies without generating a specific binder, thereby reducing tau pathology and improving motor function in vivo. [ABSTRACT FROM AUTHOR]

This paper introduces a pioneering investigation into affective pragmatics through the perspective of Darwinian Biolinguistics, an interdisciplinary field at the nexus of biological and linguistic principles. Anchored in Darwin's theory of evolution and the latest developments in neurobiology, this study delves into the influence of biological factors--especially those pertaining to the brain's emotional processing on pragmatic communication. The research posits that human emotional responses, inherent in our biological constitution, profoundly influence the usage and interpretation of language in social interactions. [ABSTRACT FROM AUTHOR]

Background: The construct of “moral injury” is used widely in the research literature and media to broadly describe the impact of events involving perceived violations of one’s sense of right and wrong (herein referred to as “potentially morally injurious events” [PMIEs]). Summary: In this theoretical review, we provided a brief overview of the “moral injury” construct and its limitations including the lack of consensus-drawn boundaries and operational definitions to guide hypothesis-driven research. We discussed whether this construct can be reliably distinguished from established psychiatric diagnoses and psychological constructs and the inherent challenges in separating or classifying the impact of high-magnitude stressful life events that likely form the majority of PMIEs. Assessments that purportedly measure “moral injury” are reviewed and limitations are discussed such as shared measurement variance with established psychological instruments. Key Messages: We identified conceptual strategies for investigating behavioral and neurobiological features of PMIEs that could be used to inform the field of traumatic stress. We concluded that the construct of “moral injury” may provide an interpretive framework for positing why someone may be beset by guilt, shame, and/or rage whereas existing psychiatric diagnoses such as post-traumatic stress disorder and depression provide comprehensive descriptions regarding what someone might experience following extremely stressful events. We proposed directions to better clarify the boundaries of “moral injury” versus established psychiatric categories that could be used to enhance the conceptualization and assessment of this construct. [ABSTRACT FROM AUTHOR]

Neuroscience should be at the core of a sound sleep health curriculum, especially in early classroom-based medical education. This article canvasses ways in which sleep medicine has been rapidly transformed by tele-sleep tools and by research on neurobiological mechanisms underlying sleep disorders and on comorbidities associated with sleep disorders, including stroke, traumatic brain injury, and movement or neurocognitive disorders. [ABSTRACT FROM AUTHOR]

Cocaine is a frequently abused and highly addictive drug that damages brain health and imposes substantial social and economic costs. Acupuncture has been used in the treatment of cocaine addiction and has been shown to improve abnormal mental and motor states. This article mainly focuses on the neurobiological mechanisms involving the central nervous system (CNS) and peripheral nervous system (PNS) that underlie the effects of acupuncture in the treatment of cocaine addiction. The central dopamine system is a key player in acupuncture treatment of cocaine addiction; the ventral tegmental area (VTA)—nucleus accumbens (NAc) signaling pathway, which has a modulatory influence on behavior and psychology after chronic use of cocaine, is a significant target of acupuncture action. Moreover, acupuncture alleviates cocaine-induced seizures or acute psychomotor responses through the paraventricular thalamus and the lateral habenula (LHb)—rostromedial tegmental (RMTg) nucleus circuits. The data suggest that acupuncture can impact various cocaine-induced issues via stimulation of diverse brain areas; nevertheless, the interconnection of these brain regions and the PNS mechanisms involved remain unknown. In this review, we also discuss the effects of specific acupuncture protocols on cocaine addiction and note that variations in needling modalities, current intensities and traditional acupuncture point locations have led to different experimental results. Therefore, standardized acupuncture protocols (with respect to stimulation methods, point locations and number of sessions) may become particularly important in future studies. [ABSTRACT FROM AUTHOR]

There is widespread scientific evidence that validates tonic immobility (TI) as part of the trauma response in victims of rape, and criminal justice practitioners are increasingly trained in trauma-informed approaches. Yet, legal and policy definitions of consent do not fully recognize TI during the incident as evidence of nonconsent. Using a systematic review of U.S. law and policy regarding sexual violence and consent, this paper analyzes the substantial legal reform of rape law and definitions of consent, suggesting ways to further integrate TI into existing law and legal practices to improve public health approaches and justice responses for victims. [ABSTRACT FROM AUTHOR]

In this paper, approximate solutions for stochastic Fitzhugh–Nagumo partial differential equations are obtained using two‐dimensional shifted Legendre polynomial (2DSLP) approximation. The problem's suitability and solvability are confirmed. The convergence analysis for the proposed methodology and the error analysis in the L2$$ {L}^2 $$ norm are carried out. Using Maple software, an algorithm is created and implemented to arrive at the numerical solution. The solution thus obtained is compared with the exact solution and the solution obtained using the explicit order RK1.5 method. [ABSTRACT FROM AUTHOR]

The task of preventing suicide in older adults is an important social burden as older adults aged above 65 are exposed to singular psychological aspects that increase suicide risks. Moreover, when an older adult corpse is found, the medico-legal inspection represents a fundamental tool to identify the exact cause of death, classifying or excluding it as suicide. In this scenario, this review aims to explore the neurobiological factors that could be related to suicidal behavior in older adults. A further goal of this review is the exploration of the medico-legal aspects surrounding older adult suicides, clarifying the importance of forensic investigation. Particularly, this review examines issues such as neurotransmitter imbalances, cognitive impairment, neuroinflammation, psychosocial factors related to geriatric suicide, and neurodegenerative diseases. Additionally, medico-legal aspects such as policy considerations, legal frameworks, mental health assessments, ethical implications and forensic investigation were explored. Considering the importance of this phenomenon, especially in western countries, a need has emerged for focused screening tools on suicidal behavior among older adults, in order to contain it. Therefore, this review makes an exhaustive appraisal of the literature giving insights into the delicate interplay between neurobiology as well as mental health in relation to older adult suicide within a medico-legal context. The comprehension of different aspects about this complex phenomenon is fundamental to propose new and more effective interventions, supporting tailored initiatives such as family support and improving healthcare, specifically towards vulnerable ageing societies to reduce older adult suicide risks. [ABSTRACT FROM AUTHOR]

Cortical organization should constrain the study of how the brain performs behavior and cognition. A fundamental concept in cortical organization is that of arealization: that the cortex is parceled into discrete areas. In part one of this report, we review how non-human animal studies have illuminated principles of cortical arealization by revealing: (1) what defines a cortical area, (2) how cortical areas are formed, (3) how cortical areas interact with one another, and (4) what "computations" or "functions" areas perform. In part two, we discuss how these principles apply to neuroimaging research. In doing so, we highlight several examples where the commonly accepted interpretation of neuroimaging observations requires assumptions that violate the principles of arealization, including nonstationary areas that move on short time scales, large-scale gradients as organizing features, and cortical areas with singular functionality that perfectly map psychological constructs. Our belief is that principles of neurobiology should strongly guide the nature of computational explanations. Petersen et al. review fundamental principles of the areal organization of the cerebral cortex. They discuss the definition, formation, interactions, and functions of cortical areas, and they identify ways in which the principles of arealization should guide human neuroimaging research. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to comprehensively report the epidemiological and clinical features of atypical anorexia nervosa (AAN) in children and adolescents. Methods: In May 2024, a systematic review was performed using Medline, Cochrane Library, ClinicalTrials.gov, and relevant websites. Following PRISMA guidelines, 234 articles were screened for studies on DSM-5-defined AAN. A standardized checklist—the JBI critical appraisal tool—was adopted in assessing methodology, and 13 retained studies passed the screening and critical appraisal process for the final review. The Newcastle–Ottawa Scale was utilized to assess the risk of bias in cohort and case–control studies, ensuring a comprehensive evaluation of methodological quality. Results: AAN prevalence in young age groups is 2.8%, with a cumulative 2.8% incidence over 8 years. Incidence is 366 per 100,000 person-years, and the average episode duration is 11.6 months, with a 71% remission rate. Diagnostic persistence for AAN is less stable than other restrictive feeding and eating disorders (FEDs). AAN individuals exhibit higher EDE-Q scores, more severe distress, and distinct BMI differences compared to those with anorexia nervosa and controls. The diagnostic transition from the DSM-IV to the DSM-5 shows that AAN patients are predominantly female, slightly older, and with higher weight. Conclusions: This study yields concrete insights into the features of AAN in the developmental age, highlighting demographic variations, clinical presentations, and treatment outcomes. Recognizing the unique challenges faced by AAN individuals is vital for tailoring effective interventions and improving overall care within the FED spectrum. [ABSTRACT FROM AUTHOR]

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00–0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals. [ABSTRACT FROM AUTHOR]

Nematoda is a diverse phylum that is estimated to contain more than a million species. More than 4,100 of these species have the ability to parasitize plants and cause agricultural losses estimated at US $173 billion annually. This has led to considerable research into their biology to minimize crop losses via control methods. At the infancy of plant-parasitic nematode molecular biology, researchers compared nematode genomes, genes, and biological processes to the model nematode species Caenorhabditis elegans, which is a free-living bacterial feeder. This well-annotated and researched model nematode assisted the molecular biology research, e.g., with genome assemblies, of plant-parasitic nematodes. However, as research into these plant parasites progressed, the necessity of relying on the free-living relative as a reference has reduced. This is partly driven by revealing the considerable divergence between the two types of nematodes both genomically and anatomically, forcing comparisons to be redundant as well as the increased quality of molecular plant nematology proposing more suitable model organisms for this clade of nematode. The major irregularity between the two types of nematodes is the unique anatomical structure and effector repertoire that plant nematodes utilize to establish parasitism, which C. elegans lacks, therefore reducing its value as a heterologous system to investigate parasitic processes. Despite this, C. elegans remains useful for investigating conserved genes via its utility as an expression system because of the current inability to transform plant-parasitic nematodes. Unfortunately, owing to the expertise that this requires, it is not a common and/or accessible tool. Furthermore, we believe that the application of C. elegans as an expression system for plant nematodes will be redundant once tools are established for stable reverse-genetics in these plant parasites. This will remove the restraints on molecular plant nematology and allow it to excel on par with the capabilities of C. elegans research. [ABSTRACT FROM AUTHOR]

Economics and biology have long been overlapping and mutually enriching fields. We contribute to this cross-fertilization by spelling out the implications for economic theory of some recent insights from evolutionary neurobiology. We note that dynamic homeostasis, a core feature of life processes, has shaped social interactions at varied stages of evolution – from the patterns of competition and cooperation among early life forms to the complex process of human cultures. The resulting homeostatic perspective is not compatible with several leading economic theories but does provide a biological footing for promising concepts such as ecological rationality, heuristics, heterogeneity of economic agents, and complex, self-organizing dynamics. [ABSTRACT FROM AUTHOR]

Hands-on activities are considered to be particularly suitable for generating long-term knowledge that increases environmentally friendly behaviour. Appropriate flagship species in a respective curricular context can enable high-quality education. We have developed a teaching concept and material for hands-on activities with bumblebees. This includes aspects of outdoor bumblebee-keeping in a teaching unit, together with the identification of bumblebee species and conservation activity in the context of biodiversity; bumblebees can act as umbrella species because their conservation needs incidentally protect other species. Moreover, the project involves keeping bumblebees indoors in a teaching unit that covers ethology and neurobiology. A total sample size of 188 German high school students from the fifth to seventh grade (lower and intermediate secondary-school levels) participated in the project. We measured students' knowledge about bumblebees in general and insect decline, as well as fear of bumblebees in a pre-test, post-test and follow-up test. Learning enjoyment was also measured in the post-test. Students acquired long-lasting knowledge and considerably enjoyed the learning experience. Fear of bumblebees decreased long-term, although knowledge that bumblebees can sting increased. [ABSTRACT FROM AUTHOR]

Interdisciplinary study in neurobiology, liberation psychology, and social work highlight the ways in which the brain is related to various cognitive, personality, and behavioral characteristics within a cultural context by blurring lines between dimensions, such as nature and nurture, person and environment, and micro and macro. This paper considers study findings that generate potential clinical social work strategies that are particularly relevant for communities of color experiencing ethno-racial trauma. The purpose of this paper is to support clinical practitioners' efforts to use holistic approaches and practices by incorporating the "bio" component of the biopsychosocial paradigm as it relates to racism. There are at least three pathways by which racism may produce neurobiological consequences that affect the biopsychosocial functioning of populations of color: (a) socio-structural/environmental, (b) stress and/or trauma, and (c) epigenetics. The Flint, Michigan water crisis—wherein the local government allowed lead to contaminate the city's drinking water causing negative health (brain and body) consequences for Flint residents, a predominantly Black and Brown community—presents an example of the intersecting pathways and autopoietic nature of racism that infects relationships, institutions and systems; causes dehumanizing affects; and produces ill effects as evidenced by racial health inequities. The issues, such as racial health inequities, that social workers struggle to resolve tend to be complex and multi-dimensional. Therefore, comprehensive practice is needed to support healthy biopsychosocial functioning. As such, this paper offers Critical Clinical Social Work Practice (CCSWP) informed by the Critical Transformative Potential Development (CTPD) framework. CTPD centers a trauma-informed and healing-centered approach to CCSWP by transforming consciousness into action to change self, relationships, and environment; ideally, working cyclically from the molecular to the macro. Given the field's enduring commitment to social justice, the biopsychosocial model, and the person-in-environment perspective, social work is in a unique position to critically consider how brain health (bio) is affected by trauma (psycho) stemming from racism (social). These multi-level (molecular to macro) considerations empower clinical social workers to innovate integrated strategies that can overcome complex challenges perpetuating racial health inequities. [ABSTRACT FROM AUTHOR]

Need states are internal states that arise from deprivation of crucial biological stimuli. They direct motivation, independently of external learning. Despite their separate origin, they interact with reward processing systems that respond to external stimuli. This article aims to illuminate the functioning of the needing system through the lens of active inference, a framework for understanding brain and cognition. We propose that need states exert a pervasive influence on the organism, which in active inference terms translates to a "pervasive surprise"—a measure of the distance from the organism's preferred state. Crucially, we define needing as an active inference process that seeks to reduce this pervasive surprise. Through a series of simulations, we demonstrate that our proposal successfully captures key aspects of the phenomenology and neurobiology of needing. We show that as need states increase, the tendency to occupy preferred states strengthens, independently of external reward prediction. Furthermore, need states increase the precision of states (stimuli and actions) leading to preferred states, suggesting their ability to amplify the value of reward cues and rewards themselves. Collectively, our model and simulations provide valuable insights into the directional and underlying influence of need states, revealing how this influence amplifies the wanting or liking associated with relevant stimuli. [ABSTRACT FROM AUTHOR]

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The human brain, a complex organ pivotal to the nervous system, orchestrates crucial functions for cognition and behavior. This research advances 3D brain cell modeling, overcoming traditional limitations. While mouse models present challenges in translatability to human brains, the evolution from non-invasive imaging to 3D culture models, specifically brain organoids, holds promise for understanding neurological disorders. Current limitations in 3D brain cell models, particularly the use of pluripotent stem cells, include high costs, extended development times, and a notable failure rate. In response, this study introduces a novel approach utilizing glial and neuron cells, significantly reducing costs and development time while maintaining a low failure rate. Experimental results demonstrate the successful creation and differentiation of 3D brain models, addressing key limitations. The developed mini-brain model, sustained for 21 days, exhibits resilience and responds differentially to glucose treatment, suggesting potential implications for brain morphology. Cell viability assessments confirm the predominantly live nature of the model, providing a foundation for future investigations. While limitations include a focus on two cell types and 21 days, future endeavors aim to diversify cell types and extend the maturation period. This research marks a significant stride in cost-effective, efficient, and ethical 3D brain modeling, laying the groundwork for continued exploration and comparison with established brain models. [ABSTRACT FROM AUTHOR]

The role of experience in the process of behavioral refinement has been undertheorized by philosophers of neuroscience and neuroscientists. By examining sleep studies in behavioral neurobiology, I show that scientists frequently invoke a variety of lived experiences—what I call experientially derived notions—to refine the behavior under investigation. Of note, these behaviors must remain sufficiently fuzzy throughout experimentation to permit refinement. The aim of this article is to recognize that neuroscientists' use of lived experience necessarily helps refine behaviors and render those behavioral terms relevant to human life. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide; therefore, since its initial description, significant progress has been made, yet a mystery remains regarding its pathogenesis and elusive root cause. The widespread distribution of pathological α-synuclein (αSyn) aggregates throughout the body raises inquiries regarding the etiology, which has prompted several hypotheses, with the most prominent one being αSyn-associated proteinopathy. The identification of αSyn protein within Lewy bodies, coupled with genetic evidence linking αSyn locus duplication, triplication, as well as point mutations to familial Parkinson's disease, has underscored the significance of αSyn in initiating and propagating Lewy body pathology throughout the brain. In monogenic and sporadic PD, the presence of early inflammation and synaptic dysfunction leads to αSyn aggregation and neuronal death through mitochondrial, lysosomal, and endosomal functional impairment. However, much remains to be understood about αSyn pathogenesis, which is heavily grounded in biomarkers and treatment strategies. In this review, we provide emerging new evidence on the current knowledge about αSyn's pathophysiological impact on PD, and its presumable role as a specific disease biomarker or main target of disease-modifying therapies, highlighting that this understanding today offers the best potential of disease-modifying therapy in the near future. [ABSTRACT FROM AUTHOR]

Chronic stress is a significant factor affecting modern society, with profound implications for both physical and mental health. Central to the stress response is cortisol, a glucocorticoid hormone produced by the adrenal glands. While cortisol release is adaptive in acute stress, prolonged exposure to elevated levels can result in adverse effects. This manuscript explores the neurobiological implications of chronic stress and its impact on metabolic dysregulation, particularly in the context of inflammatory bowel diseases (IBDs). The hypothalamic–pituitary–adrenal (HPA) axis regulates cortisol production, which influences metabolism, immune response, and neurobiology. Elevated cortisol levels are associated with the development and exacerbation of metabolic disorders like IBD and contribute to neurodegenerative processes, including cognitive impairments and increased susceptibility to psychiatric conditions. The interaction between cortisol and its receptors, particularly glucocorticoid receptors, underscores the complexity of these effects. This review aims to elucidate the mechanisms through which chronic stress and cortisol dysregulation impact metabolic health and neurobiological function, providing insights into potential therapeutic strategies for mitigating these effects. [ABSTRACT FROM AUTHOR]

Background: Substance use disorders (SUDs) and mental health disorders (MHDs) are significant public health challenges with far-reaching consequences on individuals and society. Dual diagnosis, the coexistence of SUDs and MHDs, poses unique complexities and impacts treatment outcomes. A research landscape analysis was conducted to explore the growth, active countries, and active journals in this field, identify research hotspots, and emerging research topics. Method: A systematic research landscape analysis was conducted using Scopus to retrieve articles on dual diagnosis of SUDs and MHDs. Inclusion and exclusion criteria were applied to focus on research articles published in English up to December 2022. Data were processed and mapped using VOSviewer to visualize research trends. Results: A total of 935 research articles were found. The number of research articles on has been increasing steadily since the mid-1990s, with a peak of publications between 2003 and 2012, followed by a fluctuating steady state from 2013 to 2022. The United States contributed the most articles (62.5%), followed by Canada (9.4%). The Journal of Dual Diagnosis, Journal of Substance Abuse Treatment, and Mental Health and Substance Use Dual Diagnosis were the top active journals in the field. Key research hotspots include the comorbidity of SUDs and MHDs, treatment interventions, quality of life and functioning, epidemiology, and the implications of comorbidity. Emerging research topics include neurobiological and psychosocial aspects, environmental and sociocultural factors, innovative interventions, special populations, and public health implications. Conclusions: The research landscape analysis provides valuable insights into dual diagnosis research trends, active countries, journals, and emerging topics. Integrated approaches, evidence-based interventions, and targeted policies are crucial for addressing the complex interplay between substance use and mental health disorders and improving patient outcomes. [ABSTRACT FROM AUTHOR]

To elucidate the brain‐wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information‐resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time‐series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally‐specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole‐brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean‐field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) affects 174 million women worldwide and is characterized by profound sadness, anxiety, irritability, and debilitating fatigue, which disrupt maternal caregiving and the mother–infant relationship. Limited pharmacological interventions are currently available. Our understanding of the neurobiological pathophysiology of PPD remains incomplete, potentially hindering the development of novel treatment strategies. Recent hypotheses suggest that PPD is driven by a complex interplay of hormonal changes, neurotransmitter imbalances, inflammation, genetic factors, psychosocial stressors, and hypothalamic–pituitary–adrenal (HPA) axis dysregulation. This narrative review examines recent clinical studies on PPD within the past 15 years, emphasizing advancements in neuroimaging findings and blood biomarker detection. Additionally, we summarize recent laboratory work using animal models to mimic PPD, focusing on hormone withdrawal, HPA axis dysfunction, and perinatal stress theories. We also revisit neurobiological results from several brain regions associated with negative emotions, such as the amygdala, prefrontal cortex, hippocampus, and striatum. These insights aim to improve our understanding of PPD's neurobiological mechanisms, guiding future research for better early detection, prevention, and personalized treatment strategies for women affected by PPD and their families. [ABSTRACT FROM AUTHOR]

Background and objectives: The advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses. Methods: We classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up. Results: Compared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RDvalues correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcomemeasures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of a-synuclein and b-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year. Conclusions: The PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of whitematter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype. [ABSTRACT FROM AUTHOR]

This paper explores the mechanisms that lead to a destructive tendency in the formation and functioning of the psychic apparatus, to the characteristic states of subjects who are drawn to non-life. The dynamics of the primary mother-child relationship involve a structural interaction between mind and body, subject and object. The dialectic between the life drive and the death drive is conceptualized as the structuring of homeostatic dynamic equilibria, in which both drives belong to the living, provided they are kept in a non-isolated system. This conception has analogies with other disciplines that have changed their paradigms, such as neurobiology, which, for living beings in open systems, hypothesises a continuous interconnected Becoming of undivided separation and of discontinuity. In unitary psyche-soma functioning, a dynamic homoeostatic balance marks the state of health of the relating subject; or if, instead, the system is isolated, a pathological dysregulation depending on the emotional-affective vicissitudes it undergoes. Two clinical cases illustrate these dynamics. For this tendency on the level of the somatopsychic unit, the name alloiosis has been put forward, in analogy with cellular apoptosis. [ABSTRACT FROM AUTHOR]

Although stress is an everyday fact of life, it can lead to poor health outcomes, particularly when intense or prolonged. However, humans have unique cognitive abilities and thus may be able to combat stress by engaging critical psychological defence mechanisms. In this review, we discuss the field of mind‐body medicine, which focuses on improving our understanding of the mechanisms underlying this response and developing interventions that might be used to limit the effects of chronic stress. We review the findings of past and current research in this field that has focused on the impact of psychological, emotional, and behavioural factors, including love, social connectedness, and happiness on human health and the amelioration of pain as well as other signs and symptoms of disease. While these studies have not yet led to confirmed, quantifiable conclusions, the overall weight of evidence suggests that happiness (defined as a personal sense of well‐being) may be directly associated with improved health parameters and reductions in debilitating symptoms. Collectively, these findings suggest that interventions designed to promote stress mitigation, notably those that encourage social activity, may lead to significant improvements in human health. [ABSTRACT FROM AUTHOR]

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo. [ABSTRACT FROM AUTHOR]

Perinatal depression (PND) and perinatal anxiety are common conditions that can arise during or after pregnancy and can have a major impact on patients and their families. A potential outcome of PND includes death by suicide, a leading cause of maternal mortality. This article provides an overview of these conditions, including discussion of neurobiology, risk factors, warning signs for individuals at risk for suicide and/or infant harm, and relevant screening tools. Considerations for psychotherapy and pharmacotherapy are highlighted, and an overview of neuroactive steroid gamma-aminobutyric acid A receptor positive allosteric modulators, a newer pharmacologic treatment option for postpartum depression, is provided. [ABSTRACT FROM AUTHOR]

The phenomenon of aesthetic chills—shivers and goosebumps associated with either rewarding or threatening stimuli—offers a unique window into the brain basis of conscious reward because of their universal nature and simultaneous subjective and physical counterparts. Elucidating the neural mechanisms underlying aesthetic chills can reveal fundamental insights about emotion, consciousness, and the embodied mind. What is the precise timing and mechanism of bodily feedback in emotional experience? How are conscious feelings and motivations generated from interoceptive predictions? What is the role of uncertainty and precision signaling in shaping emotions? How does the brain distinguish and balance processing of rewards versus threats? We review neuroimaging evidence and highlight key questions for understanding how bodily sensations shape conscious feelings. This research stands to advance models of brain-body interactions shaping affect and may lead to novel nonpharmacological interventions for disorders of motivation and pleasure. [ABSTRACT FROM AUTHOR]

This article explores the parallax relationship that runs through two coexisting, yet irreconcilable viewpoints in Gish Jen's World and Town: mind/body, reason/faith, and self/other, respectively, in the scientific, religious, and political realms. The first part, "A World of Neuro-Cognitivism," probes the neurobiological parallax binary constructed by Carter and Hattie—the neuronal and the mental. The second part, "A Town of Faith," investigates another parallax relationship between reason and faith (or fact and faith) through the beliefs of three characters—Ginny (a fundamentalist), Hattie (a Unitarian), and Carter (a postmodern cynic). Finally, "The Other Coming to Town" scrutinizes the portrayal of the Chhung family as an intruding other and the potential for a social bond with them, as suggested by Jen. The article concludes with a critique of Jen's strategy; the author redirects the focus away from the perspectival multiplicity through the binary to the one. [ABSTRACT FROM AUTHOR]

The recent worldwide surge of warfare and hostilities exposes increasingly large numbers of individuals to traumatic events, placing them at risk of developing posttraumatic stress disorder (PTSD) and challenging both clinicians and service delivery systems. This overview summarizes and updates the core knowledge of the genetic, molecular, and neural circuit features of the neurobiology of PTSD and advances in evidence-based psychotherapy, pharmacotherapy, neuromodulation, and digital treatments. While the complexity of the neurobiology and the biological and clinical heterogeneity of PTSD have challenged clinicians and researchers, there is an emerging consensus concerning the underlying mechanisms and approaches to diagnosis, treatment, and prevention of PTSD. This update addresses PTSD diagnosis, prevalence, course, risk factors, neurobiological mechanisms, current standard of care, and innovations in next-generation treatment and prevention strategies. It provides a comprehensive summary and concludes with areas of research for integrating advances in the neurobiology of the disorder with novel treatment and prevention targets. [ABSTRACT FROM AUTHOR]

Background: Exposure to stress during childhood and adolescence is a risk factor for alcohol use disorder (AUD) and comorbid conditions, including posttraumatic stress disorder (PTSD). We previously established an adolescent social isolation (SI) model that leads to the emergence of a wide range of behavioral risk factors for AUD, including increased anxiety‐like behavior, locomotor activity, and ethanol consumption in male and female rats. Here, we sought to test the hypothesis that SI may increase vulnerability to single prolonged stress (SPS), a rodent model of PTSD. Methods: Female Long Evans rats (n = 8/group) were either single‐housed or group‐housed (GH) (4/cage) on postnatal day 21. One week later, rats underwent testing in the open field test (OFT), elevated plus‐maze (EPM), and successive alleys test (SAT). Following initial behavioral testing, a subset of SI/GH rats were exposed to SPS. All rats were then tested on the novelty‐suppressed feeding test (NSFT) followed by fear conditioning and home cage two‐bottle choice to assess ethanol consumption. Results: SI significantly increased activity in the OFT and anxiety‐like behavior on the SAT, but not the EPM. While SI and SPS alone had no effect on the NSFT, exposure to both stressors significantly increased approach latency. Complex effects of stress history were observed across a 3‐day fear conditioning paradigm and no group differences were observed with home cage ethanol consumption, regardless of prior ethanol exposure. Conclusions: The results from this study provide novel evidence that SI interacts with SPS in female rats to influence behavior in assays of unconditioned anxiety‐like behavior (NSFT) and conditioned fear. Surprisingly, stress exposure had no effect on home cage ethanol consumption. Ultimately, these models provide useful avenues to examine the interaction between stressful experiences, alcohol exposure, biological sex, and the neurobiological adaptations underlying potential risk factors for psychiatric conditions. [ABSTRACT FROM AUTHOR]

With the objective to predict and pre-empt the emergence of political violence, the US Department of Defence (DoD) has devoted increasing attention to the intersection between neurobiology and artificial intelligence. Concepts such as 'cognitive biotechnologies', 'digital biosecurity' and large-scale collection of 'neurodata' herald a future in which neurobiological intervention on a global scale is believed to come of age. This article analyses how the relationship between neurobiology and AI – between the human and the machine – is conceived, made possible, and acted upon within the SMA programme, an interdisciplinary research programme sponsored by the DoD. By showcasing the close intersection between the computer sciences and the neurosciences within the US military, the article questions descriptions of algorithmic governmentality as decentring the human, and as juxtaposed to biopolitical techniques to regulate processes of subjectivity. The article shows that within US military discourse, new biotechnologies are seen to engender algorithmic governmentality a biopolitical dimension, capable of monitoring and regulating emotions, thoughts, beliefs, and subjectivity on population level, particularly targeting the minds and brains of 'vulnerable' populations in the global South. [ABSTRACT FROM AUTHOR]

Background: To date, there is no effective treatment for Alzheimer's disease (AD), a progressive neurodegenerative disorder that is increasing in prevalence worldwide. The objective of this review was to summarize the core targets and signaling pathways involved in acupuncture treatment for AD. Methods: We reviewed numerous signaling pathways, including mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase–protein kinase B (PI3 K/Akt), adenosine monophosphate–activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), nuclear factor (NF)-kB, p53, Wnt, nitric oxide (NO), Janus kinase / signal transducer and activator of transcription (JAK/ STAT), RhoA/ROCK (Rho-associated protein kinase) and Ca2+/ calmodulin-dependent protein kinase II (CaMKII) / cyclic adenosine monophosphate-response element-binding protein (CREB). The relevant data were obtained from PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases. Results: In summary, the effects of acupuncture are mediated by multiple targets and pathways. Furthermore, acupuncture can improve pathological changes associated with AD (such as abnormal deposition of amyloid (A)β, tau hyperphosphorylation, synaptic dysfunction and neuronal apoptosis) through multiple signaling pathways. Conclusion: Overall, our findings provide a basis for future research into the effects of acupuncture on AD. [ABSTRACT FROM AUTHOR]

The pleomorphic adenoma gene 1 (Plag1) is a transcription factor involved in the regulation of growth and cellular proliferation. Here, we report the spatial distribution and functional implications of PLAG1 expression in the adult mouse brain. We identified Plag1 promoter-dependent β-galactosidase expression in various brain structures, including the hippocampus, cortex, choroid plexus, subcommisural organ, ependymal cells lining the third ventricle, medial and lateral habenulae and amygdala. We noted striking spatial-restriction of PLAG1 within the cornu ammonis (CA1) region of the hippocampus and layer-specific cortical expression, with abundant expression noted in all layers except layer 5. Furthermore, our study delved into the role of PLAG1 in neurodevelopment, focusing on its impact on neural stem/progenitor cell proliferation. Loss of Plag1 resulted in reduced proliferation and decreased production of neocortical progenitors in vivo, although ex vivo neurosphere experiments revealed no cell-intrinsic defects in the proliferative or neurogenic capacity of Plag1-deficient neural progenitors. Lastly, we explored potential target genes of PLAG1 in the cortex, identifying that Neurogenin 2 (Ngn2) was significantly downregulated in Plag1-deficient mice. In summary, our study provides novel insights into the spatial distribution of PLAG1 expression in the adult mouse brain and its potential role in neurodevelopment. These findings expand our understanding of the functional significance of PLAG1 within the brain, with potential implications for neurodevelopmental disorders and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that intact social bonds are protective against age-related morbidity, while bond disruption and social isolation increase the risk for multiple age-related diseases. Social attachments, the enduring, selective bonds formed between individuals, are thus essential to human health. Socially monogamous species like the prairie vole (M. ochrogaster) form long-term pair bonds, allowing us to investigate the mechanisms underlying attachment and the poorly understood connection between social bonds and health. In this review, we explore several potential areas of focus emerging from data in humans and other species associating attachment and healthy aging, and evidence from prairie voles that may clarify this link. We examine gaps in our understanding of social cognition and pair bond behavior. Finally, we discuss physiologic pathways related to pair bonding that promote resilience to the processes of aging and age-related disease. Advances in the development of molecular genetic tools in monogamous species will allow us to bridge the mechanistic gaps presented and identify conserved research and therapeutic targets relevant to human health and aging.

Traumatic stress increases the risk for mental health conditions and adversely impacts health, academic performance, and coping. Transgender and gender diverse (TGD) youth experience higher rates of abuse and maltreatment and interpersonal and community-embedded discrimination than their cisgender peers. Neurobiologic stress responses and social stress theory provide useful frameworks for understanding the effects of discrimination, stigma, and rejection. Despite facing higher rates of interpersonal trauma, TGD youth are quite resilient when able to access supports and affirming trauma-informed services. Clinicians play an important role in identifying and addressing traumatic stress impacting TGD youth and bolstering resilience.

An increasingly popular animal model for studying the neural basis of social behavior, cognition, and communication is the common marmoset (Callithrix jacchus). Interest in this New World primate across neuroscience is now being driven by their proclivity for prosociality across their repertoire, high volubility, and rapid development, as well as their amenability to naturalistic testing paradigms and freely moving neural recording and imaging technologies. The complement of these characteristics set marmosets up to be a powerful model of the primate social brain in the years to come. Here, we focus on vocal communication because it is the area that has both made the most progress and illustrates the prodigious potential of this species. We review the current state of the field with a focus on the various brain areas and networks involved in vocal perception and production, comparing the findings from marmosets to other animals, including humans.

Fear and anxiety play a central role in mammalian life, and there is considerable interest in clarifying their nature, identifying their biological underpinnings, and determining their consequences for health and disease. Here we provide a roundtable discussion on the nature and biological bases of fear- and anxiety-related states, traits, and disorders. The discussants include scientists familiar with a wide variety of populations and a broad spectrum of techniques. The goal of the roundtable was to take stock of the state of the science and provide a roadmap to the next generation of fear and anxiety research. Much of the discussion centered on the key challenges facing the field, the most fruitful avenues for future research, and emerging opportunities for accelerating discovery, with implications for scientists, funders, and other stakeholders. Understanding fear and anxiety is a matter of practical importance. Anxiety disorders are a leading burden on public health and existing treatments are far from curative, underscoring the urgency of developing a deeper understanding of the factors governing threat-related emotions.

Adverse childhood experiences research has shown that supportive and secure attachment experiences can buffer against stress exposure during periods of high brain development and promote new patterns of tolerance to stress. This article draws on attachment theory to critically examine the importance of positive relationships for youth who have experienced trauma in promoting the development of neural pathways associated with social and emotional well-being, self-regulation, and stress tolerance. Grounded in a neurobiological understanding of disrupted attachments in the wake of trauma, this article examines the role of sport as a form of tolerable stress. In the presence of supportive relationships (coaches, mentors, peers), sport is uniquely suited to introduce stress in manageable doses and promote body awareness, regulation, and cognitive capacities to offset the long-term negative impacts of toxic stress on developing youth. [ABSTRACT FROM AUTHOR]

The extensive literature on the potent role negative thoughts about pain have on the experience of pain and pain-related suffering has documented associations with important neurobiological processes involved in amplifying nociceptive signals. We focus this review on pain catastrophizing (pCAT)— appraisals of pain as threatening, overwhelming, and unmanageable— and review the evidence that these thoughts are learned in childhood through experience and observation of others, particularly caretakers and parents. For children who have learned pCAT, repeated exposures to pain over time activate pCAT and likely contribute to further amplification of pain through changes in the neurobiological pain regulatory systems, which overlap with those regulating the stress response. We propose that repeated pain and stress exposures throughout childhood, adolescence, and into adulthood alter the neurobiology of pain via a repetitive positive feedback loop that increases risk for heightened pain sensitivity over time with repeated exposures. At some point, often precipitated by an acute episode of pain and possibly influenced by allostatic load, pCAT contributes to persistence of episodic or acute pain and exacerbates pain-related suffering. This developmental trajectory is not inevitable, as the impact of pCAT on pain and pain-related suffering can be influenced by various factors. We also present future directions for work in this area. [ABSTRACT FROM AUTHOR]

This paper uses abduction to propose a theory of addictive desire that is based on a dual dysfunction in learning and motivation. The theory is termed the Coherent Dual Theory of Addictive Desire (CDT) because it proposes that a dual dysfunction lies at the heart of addictive desire. This paper first lays out CDT in psychological terms. It then focuses on how CDT coheres with both the neurobiology and phenomenology of addictive desire, granting the theory empirical support and more explanatory power. The paper concludes by addressing an objection from opponent process theory. The result is a theory of addictive desire that contains multiple abductive virtues: It is simple, general, testable, and coherent on the levels of neurobiology, psychology, and phenomenology. [ABSTRACT FROM AUTHOR]

While the two types of intransitive verbs, i.e. unergative and unaccusative, are hypothesised to be syntactically represented, many have proposed a semantic account where abstract properties related to agentivity and telicity, often conceptualised as binary properties, determine the classification. Here we explore the extent to which graded, embodied features rooted in neurobiological systems contribute to the distinction, representing verb meanings as continuous human ratings over various experiential dimensions. Unlike prior studies that classified verbs based on categorical intuition, we assessed the degree of unaccusativity by acceptability of the prenominal past participle construction, one of the unaccusativity diagnostics. Five models were constructed to explain these data: categorical syntactic/semantic, feature-based event-semantic, experiential, and distributional models. The experiential model best explained the diagnostic test data, suggesting that the unaccusative/unergative distinction may be an emergent phenomenon related to differences in underlying experiential content. The experiential model's advantages, including interpretability and scalability, are also discussed. [ABSTRACT FROM AUTHOR]

Background: The influx of patients in the acute care setting with opioid use disorder (OUD) has outpaced many hospitals' ability to educate interprofessional staff. This creates distressing experiences for interprofessional staff and patients, leading to moral distress and burnout in staff and poor patient outcomes. Objective: The purpose of this study was to improve interprofessional staff knowledge, attitudes, and perceptions toward working with patients who have OUD using a blended classroom-simulation-based curriculum. Methods: A preintervention and postintervention design was selected. Interprofessional staff (n=46) participated in a blended classroom-simulation educational intervention focused on the neurobiology of OUD, stigma reduction, pain management, and harm reduction principles, followed by 3 high-fidelity simulation scenarios. Participants completed the Drug and Drug Problems Perceptions Questionnaire to measure staff self-perceived knowledge, skills, and attitudes when working with patients who use drugs before, immediately after, and again 3 and 6months postintervention. Results: Most respondents were nurses with an average of 7.6 (SD, 9.6) years of experience. The majority did not have prior training in substance use disorder before (75.6%). There was a statistically significant decrease in mean Drug and Drug Problems Perceptions Questionnaire scores across the total score mean: 55.2 (95% confidence interval, 52.2-58.3) versus 45.5 (95% confidence interval, 43.9-47.1), P<.001. Decreased score indicates improved attitude and perception. Discussion: A curriculum consisting of a blended classroom-simulation intervention was successful at improving several domains regarding perceptions of caring for patients with OUD. This educational intervention can serve as a model for health care systems with goal of improving patient outcomes and staff well-being. [ABSTRACT FROM AUTHOR]