bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of the Epigenome in Brain Development, Function, and Disease
Authors: Akbarian Schahram , Fullard John F. , Girdhar Kiran , Roussos Panos 
Published: January 2025

Abstract
Psychiatric disorders have a substantial genetic component. In recent years, genome-wide association studies have identified hundreds of loci associated with increased risk for disease, including schizophrenia, bipolar disorder, and depression. The majority of these loci reside within noncoding regions of the genome, often contain many candidate variants, and are thought to exert their effects by disrupting the function of DNA elements required for the optimal spatiotemporal regulation of gene expression. The epigenome encompasses the regulatory mechanisms governing the organization and function of the genome and is highly dynamic, displaying developmental and cell-type-specific differences. This chapter discusses the means by which analysis of the epigenome in diverse human brain cells can be used to better understand brain development and function and to pinpoint causal disease variants as well as their mechanisms of action, with the potential to identify novel therapeutic targets.
Methods for In Vivo Gene Manipulation
Authors: Monteggia Lisa M. , Xu Wei 
Published: January 2025

Abstract
Selective targeting and controlling diverse types of brain cells and their molecular processes are essential to understand brain function, elucidate the pathogenesis of mental disorders, and develop novel therapeutics for these disorders. Techniques regulating gene expression, including altering endogenous genes and introducing exogenous genes, are ways to achieve these goals. This chapter provides an overview of genetic manipulations in models systems, including the traditional transgene, knockout and knockin techniques, and the recently developed CRIPSR-Cas9 systems. It then discusses viral vectors, a collection of nanoscale vehicles that deliver genetic materials into infected cells. Each of these vectors exhibits special properties, such as infection selectivity or directional spreading along neuronal pathways, and provides versatile tools for targeting and regulating cells of interest. Thus, genetics and viral vectors offer powerful technology to delineate, monitor, and control brain circuitry to understand and potentially treat mental disorders.
Glial-Immune Mechanisms of Schizophrenia
Authors: Teymouri Kowsar , Ebrahimi Mahbod , Pouget Jennie G. , Kennedy James L. 
Published: January 2025

Abstract
This chapter reviews the emerging body of genetic and immunological evidence that provides support for immune disturbances in schizophrenia. Genome-wide association studies have identified 287 gene loci associated with schizophrenia, including several genes that appear to have dual roles based on their expression in both the central nervous system and immune cells. In addition, studies have shown correlations between increased peripheral inflammatory markers and schizophrenia risk, suggesting the involvement of inflammation. Moreover, the complement system is implicated in schizophrenia given that two genes, complement component 4 (C4) and CUB and SUSHI Multiple Domains 1 (CSMD1), may modulate schizophrenia risk via synaptic pruning. Positron emission tomography studies have further shown that microglial activation may be important for overpruning of synapses in schizophrenia. Overall, findings from immunogenetic studies in particular have identified potential pathogenic mechanisms such as C4 and CSMD1 as potential therapeutic targets for novel drug development in schizophrenia.
Translational Models for Psychosis
Authors: Corlett Philip R. 
Published: January 2025

Abstract
Computational approaches to explaining psychiatric illnesses are undergoing a renaissance. This chapter will describe computational approaches to psychotic symptoms. The approach can connect levels of explanation—from epidemiology down to circuit neuroscience. It suggests that delusions are driven by inappropriate prediction errors and hallucinations are driven by overweighted prior beliefs. Volatility processing may unite the two. When the world is perceived to be changing unpredictably an organism has two options—learn quickly to pre-empt the changes or ignore that signals that change is afoot. These may underwrite delusions and hallucinations respectively and each may be implemented in independent neural circuits. Furthermore, the social content of delusions and hallucinations demands explanation. Computational psychiatrists appeal either to a domain specific problem with social cognition or a domain general issue with inference. Future work will continue to refine the hypothesis space, ideally leading to a deeper understanding and better treatments for psychosis.
Novel Treatments for Schizophrenia
Authors: Paul Steven M. , Breier Alan 
Published: January 2025

Abstract
Antipsychotic drugs (APDs) have been available to treat patients with schizophrenia for more than 70 years. All currently available APDs share the common mechanism of antagonizing or blocking dopamine D2 receptors. Given the inadequate outcomes for patients with schizophrenia and the limitations of current APDs, new treatments with novel mechanisms are desperately needed. Progress to find novel therapies for schizophrenia has been slow, in part because its etiology and pathophysiology are still poorly understood. This chapter reviews potential novel APDs and their respective therapeutic targets, with a focus on compounds and targets for which recent clinical studies have yielded encouraging results, unambiguously negative results that have proven informative, or novel compounds that are currently under active investigation. With the prospect of several novel mechanistically distinct APDs on the horizon, such drugs used alone or in combination may result in markedly improved functional outcomes for patients living with schizophrenia.
Diagnostic Concepts and Epidemiology of Bipolar Disorder
Authors: Merikangas Kathleen R. , Stapp Emma K. 
Published: January 2025

Abstract
This chapter summarizes the magnitude, impact, comorbidity, and consequences of bipolar disorder. The aggregate lifetime prevalence rate of bipolar I disorder is approximately 1%, but as many as 5% or 6% of adults may manifest the broader spectrum of bipolar disorder. The onset of bipolar disorder occurs before age 30 years in nearly all of those who experience this condition. Comorbidity is pervasive among both adolescents and adults with bipolar disorder in the general population, suggesting disturbances in multiple systems of emotion, cognition, and behavior. Consequences of bipolar disorder include the development of comorbid medical and mental disorders, including substance use disorders. The occupational, economic, and social consequences are associated with substantial disability. The increased mortality from medical conditions, particularly cardiovascular disease and suicide, is particularly striking.
Molecular Neuroimaging in Substance Use Disorders
Authors: London Edythe D. , Robertson Chelsea L. , Prins Terry J. 
Published: January 2025

Abstract
This chapter describes the molecular neuroimaging techniques of positron emission tomography and single-photon emission tomography and the findings obtained in studies of chronic drug misuse and the behavioral states that perpetuate it. A deficit in the dopamine system, involving dopamine D2-type receptor availability, is common among drug use disorders. Studies of stimulant use disorders provide evidence for an imbalance between D2- and D1-type receptors, with links to impulsivity and cognitive deficits. Also common across addictions is a role of the orbitofrontal cortex in craving. More limited studies of serotonin and opioid systems show abnormalities in alcohol and stimulant use disorders that vary with duration of abstinence. Human molecular neuroimaging studies of opioid system markers, other than the μ-opioid receptor, and of other neurochemical and neuromodulatory systems are lacking. The field can benefit from large studies with standardization of methodology and from development of new radiolabeled probes for understudied systems.
Cellular and Molecular Mechanisms of Substance Use Disorders
Authors: Reissner Kathryn J. 
Published: January 2025

Abstract
Drug use results in both acute and long-lasting cellular adaptations in the brain. Preclinical animal models allow for investigation of cellular and molecular responses to drugs in the brain, as well as cellular correlates that drive drug taking and seeking. This chapter offers a historical perspective on studies investigating the cellular consequences of drug use and the cellular mechanisms driving drug-related behaviors in animal models. Focus in placed on both short-term consequences of acute drug exposure (“social use”) and longer lasting consequences of chronic rodent self-administration. Advancements in methodologies for optical imaging and sequencing of transcriptional responses in individual cells has further advanced the understanding of the mechanisms driving responses to drug exposure. Moreover, accumulating evidence indicates that neural responses to drug exposure vary in males and females, underscoring the importance of investigating sex-specific candidate treatment mechanisms for more effective intervention strategies.
Brain Development and the Risk for Substance Use, Misuse, and Substance Use Disorders
Authors: Ruiz Sonia G. , Casey B. J. , Baskin-Sommers Arielle 
Published: January 2025

Abstract
Adolescence is a developmental period associated with increased substance use and misuse. Typical neurodevelopmental changes in cognitive control, reward, and stress-related circuitry contribute to the vulnerability for substance use and misuse during adolescence. Specifically, an imbalance in regulation of reward and stress responsivity by cortical control circuitry is exaggerated during adolescence and appears to be associated with the eventual onset and maintenance of substance use disorders. Additional risk factors exacerbate this imbalance, including the influence of peers, early life adversity, family history of substance use disorders, pre- and postnatal substance exposure, and variations in personality traits such as impulsivity and sensation seeking. Interventions that bridge the gap between the neurodevelopmental science and intervention science have great potential for reducing the burden associated with adolescent substance use and misuse.
Genetics of Alzheimer’s Disease, Parkinson’s Disease, and Lewy Body Dementia
Authors: Renton Alan E. , Fulton-Howard Brian , Andrews Shea J. , Marcora Edoardo , Goate Alison M. 
Published: January 2025

Abstract
Genetic risk factors and pathogenic mechanisms underlying neurodegenerative diseases are being identified at unprecedented resolution, but larger and more diverse studies are needed. Increasing representation of non-European ancestry populations in neurodegenerative illness studies will enhance understanding of disease etiology and ameliorate health disparities. The genetic architecture of the neurodegenerative disorders Alzheimer’s disease (AD), Parkinson’s disease (PD), and Lewy body dementia (LBD) is primarily polygenic or oligogenic. Genetic, neuropathological, and clinical evidence suggests these disorders represent a PD–LBD–AD spectrum. AD, PD, and LBD risk alleles mediate their effects via cell type–specific pathogenic mechanisms. AD genetics converge on microglial or macrophage efferocytosis. PD and LBD genetics implicate endolysosome dysfunction potentially in neurons. Large-scale studies integrating genetics, omics, and the environment in diverse global populations will elucidate neurodegenerative disease pathogenic mechanisms and ultimately yield therapeutic interventions for equitable distribution worldwide.
Neuroimaging and Fluid Biomarkers of Alzheimer’s Disease
Authors: Gordon Brian A. , Schindler Suzanne 
Published: January 2025

Abstract
Alzheimer’s disease (AD) is a neurological disease defined by amyloid plaques and neurofibrillary tau tangles. This neuropathology can accumulate for a decade or more before the onset of dementia, and many cognitively normal older adults have some degree of AD pathology. The presence and progression of pathology can be measured using neuroimaging or fluid biomarkers obtained from the cerebrospinal fluid or blood. Imaging and biofluid measures provide complementary information, and each technique has its own strengths and limitations in terms of cost, invasiveness, and sensitivity to pathology. In addition to the core measures of amyloid and tau, there is an increasing repertoire of downstream markers of inflammation, synaptic dysfunction, hypometabolism, and cell death. Together, these biomarkers provide insights into the neurobiology of AD, play an important role in confirming the clinical diagnosis of symptomatic AD, and are increasingly integral parts of clinical trials and the development of effective treatments.
Diagnosis and Epidemiology of Pediatric Psychiatric Disorders
Authors: Janecka Magdalena , Briasouli Artemis , Khachadourian Vahe , Reichenberg Abraham 
Published: January 2025

Abstract
Pediatric psychiatric disorders are collectively very common, placing considerable burden on the affected individuals and their families, as well as health care and education systems. This chapter addresses the prevalence, life course trajectory, and heritability of five major pediatric psychiatric disorders: intellectual development disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder, obsessive–compulsive disorder, and tic disorders. The chapter presents the evidence for (a) their comorbidity with each other, and frequent co-occurrence among members of the same family; (b) continuity between these clinical constructs and the behavioral traits that underlie them; and (c) lower fecundity associated with these disorders. The chapter discusses the impact of these observations for inferring the etiology of pediatric psychiatric disorders and their risk architecture. It then discusses future directions for improved prevention and treatments.
Current Treatments for Pediatric Psychiatric Disorders
Authors: Siper Paige M. , Trelles M. Pilar , Kufert Yael , Grice Dorothy E. 
Published: January 2025

Abstract
Child psychiatry is a specialized discipline. The child psychiatry patient must be considered within the context of their current psychiatric signs and symptoms, psychosocial history, developmental stage, family structure, and any medical or neurological factors. The clinician should conduct a comprehensive assessment, including collateral sources, in order to consolidate a sound working diagnosis and treatment plan. Compared to adult psychiatry, the depth and breadth of research regarding medication and psychosocial treatments in youth are limited; however, evidence-based treatments, both pharmacological and psychotherapeutic, continue to emerge for many childhood-onset psychiatric disorders. Psychopharmacology is considered the first-line approach for attention-deficit/hyperactivity disorder, bipolar disorder, and psychotic illnesses, and it is also indicated for moderate to severe presentations of depressive and anxiety disorders, obsessive–compulsive disorder (OCD), and Tourette disorder. Specialized psychotherapies are first-line treatments for autism and mild to moderate depressive and anxiety disorders, OCD, and Tourette disorder.
Computational Psychiatry and the Bayesian Brain
Authors: Friston Karl J. , Gu Xiaosi 
Published: January 2025

Abstract
Computational psychiatry is a burgeoning field that uses formal models of brain function to characterize the mechanisms of psychopathology, with the hope that these mechanistic views can generate objective and predictive targets for treatment and intervention. This chapter introduces relevant key concepts and rationale relevant for computational psychiatry. It focuses on the Bayesian brain framework as an example to demonstrate how computational theories and models can account for false beliefs observed across many mental disorders. This framework is also compared with other formal theories of the brain. Specifically, the chapter reviews findings on delusions in schizophrenia as an example of false sensory inference; it also uses false interoceptive and interpersonal inference in autism to demonstrate the impact of faulty inference during neurodevelopment. The chapter concludes by summarizing the status quo of the field and noting future directions of research.
Psychedelic Drugs as Treatment Agents
Authors: Yehuda Rachel , Lepow Lauren A. , Bonnano Philip A. , Zaretsky Tamar Glatman , Antonio Josimar Hernandez , Jagodnik Kathleen M. 
Published: January 2025

Abstract
Psychedelics are compounds that alter consciousness. Currently, most psychedelic substances are federally illegal in the United States; however, the U.S. Food and Drug Administration has designated three psychedelic-assisted psychotherapy treatments as breakthrough therapies. Treatment with psychedelic drugs involves administering a medication only once or a few times to facilitate a psychotherapeutic process. Extrapharmacologic factors of treatment are central to the design of these trials. Recent clinical research has found large effect sizes with no serious adverse events reported. Although the basic psychopharmacology profiles of these drugs have been characterized, and neuroscientific and psychotherapeutic frameworks have been proposed, the mechanisms of action for these treatments are under active investigation. The observed durable and transdiagnostic psychiatric effects are likely partially related to their robust induction of neuroplasticity. This chapter describes the state of psychiatric research involving the two major classes of psychedelic compounds—tryptamines and phenethylamines—and their psychotherapeutic context.
Prologue
Authors: Inui Thomas S. 
Published: January 2025

Abstract
Becoming a medical professional and developing medical professionalism are dynamic activities that involve more than merely acquiring and expertly applying medical knowledge; they require reflection on the part of the learner – as well as the teacher – to consider how, what, where, and when one acquires and applies their medical knowledge and expertise. One way to engage in the kind of reflection needed toward becoming a medical professional is through writing personal narratives or analyzing others’ narratives in self-reflection exercises. In this prologue, readers delve into what it means to be a medical professional and to cultivate medical professionalism, as well as consider and analyze a personal narrative of the author. Readers are then challenged to consider their own narratives and how they have contributed to their moral development and sense of professionalism and professional values.
Assessment of Professionalism
Authors: Kachur Elizabeth Krajic 
Published: January 2025

Abstract
Professionalism has become a priority concern in healthcare professions education. Yet it is difficult to assess this competency in a valid, reliable, feasible, and fair fashion. Professional standards and behaviors are influenced by many factors, some are explicit (e.g., laws, policies), others more difficult to identify (e.g., culture, role models). This chapter provides a framework to assist educational programs with creating a comprehensive and fair assessment plan. A modified Miller’s pyramid helps organize the different types of assessment formats from knowledge-focused quizzes to reflection-focused portfolios and essays that explore the formation of professional identities. Each offers advantages and challenges that can help educators select the assessment tool that best fits their needs and resources. Although the assessment of professionalism is still an emerging field, it has become clear that programs need to develop a “system of assessments” to optimize the capture of a learner’s true level of professionalism.
Lifestyle Medicine in Patient Care
Authors: Fagundes Christopher P. , Merlo Gia , Rippe James M. 
Published: January 2025

Abstract
The biopsychosocial model assumes good health is determined by biological, psychological, and social factors that interact to promote health and disease. Lifestyle medicine is an evidence-based lifestyle therapeutic intervention—including a whole-food, plant-predominant eating pattern, regular physical activity, restorative sleep, stress management, avoidance of risky substances and positive social connection—as a primary modality, delivered by clinicians trained and certified in this specialty, to prevent, treat and often reverse chronic disease. Chronic diseases are developed, prevented, managed, and treated through a complex array of biological, psychological, and social influences. The behaviors, social connections, and emotions that characterize people’s lives shape their quality of life and physical health.
The Professionalism and Ethics of Medical Mission Work
Authors: Essig Rachael , Angelos Peter 
Published: January 2025

Abstract
Professionalism is grounded in the ethics of a given vocation. Professional conundrums can feel insurmountable even in the most regular of environments. Medical professionals entering the international setting to practice must be equipped with the knowledge of how to traverse these potentially perplexing professional quandaries. Global medicine is a fast-growing area of medical practice with medical trainees stating increased interest in participation in international venues. While international destinations provide excellent opportunities to gain diverse medical knowledge and nurture cultural sensitivity, there are many challenges that arise with minimal education on navigating them. Adding a new situation and occasionally culture and language makes ethical challenges absolute enigmas. This chapter uses a case-based approach to establish a framework for navigating new challenges in various different settings.
Professionalism in Engagement and Patient/Family Communication
Authors: Pferdehirt Ryan , Carter Brian S. 
Published: January 2025

Abstract
Professional conduct by physicians can be challenging when communicating with patients and families. Professional codes of ethics and oaths, such as the Hippocratic oath, have been a foundation for defining professionalism, yet in modern times they may be considered of limited value. A cornerstone of professionalism is meaningful communication that employs the principle of autonomy and the virtues of humility, veracity, and trust to attain true engagement. These tenets are fundamental across all professional encounters but unique differences between adult and pediatric patients require attention. For adults, professional engagement means embracing a shared decision-making model where physicians acknowledge the difference in their repository of medical knowledge and skill and the power dynamic it contributes to and the intentional and deliberate work needed to create a more shared balance. In pediatrics, professionalism is apparent when physicians act in an empathic manner with the child and parent(s) and demonstrate care. This chapter explores the value of integrating humility, empathy, and veracity into communication with patients and families and how this serves to demonstrate professionalism and build trust.
Medical Leadership, Professionalism, and Vulnerable Populations
Authors: Ghosh S. Monty 
Published: January 2025

Abstract
Background: Health, housing, and homelessness are intricately intertwined, and approaches to the care of this population require an enhanced understanding of the intersectionality of health, social services, justice systems, and policy. This chapter examines how best to approach and integrate multisystems care to provide support for vulnerable populations, as well as examine how professional development could be structured to enhance care for this population. Also examined are trauma informed care and harm reduction, as well as how trauma-informed leadership can be helpful at an organizational and systems-based level. Last, some practical tips in working with those experiencing extreme vulnerabilities are examined.