State of the Science: The Hierarchical Taxonomy of Psychopathology (HiTOP).

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a dimensional framework for psychopathology advanced by a consortium of nosologists. In the HiTOP system, psychopathology is grouped hierarchically from super-spectra, spectra, and subfactors at the upper levels to homogeneous symptom components and maladaptive traits and their constituent symptoms, and maladaptive behaviors at the lower levels. HiTOP has the potential to improve clinical outcomes by planning treatment based on symptom severity rather than heterogeneous diagnoses, targeting treatment across different levels of the hierarchy, and assessing distress and impairment separately from the observed symptom profile.

Protocol for isolating extracellular vesicles from pancreatic cancer cells for liver metastatic niche research.

Extracellular vesicles (EVs) are secreted, cell-derived, membrane-bound compartments implicated in various diseases for their ability to influence distant targets and as carriers of biomarkers. Here, we present a protocol for separating EVs from mammalian pancreatic cancer cells and their characterization using western blot and electron microscopy. We then demonstrate how they are utilized to affect tumor development in a murine model of metastatic pancreatic cancer including a method to quantify hepatic tumor burden in histologic samples.

Transglutaminase 2 knockout mice are protected from bleomycin-induced lung fibrosis with preserved lung function and reduced metabolic derangements.

Pulmonary fibrosis is an interstitial scarring disease of the lung characterized by poor prognosis and limited treatment options. Tissue transglutaminase 2 (TG2) is believed to promote lung fibrosis by crosslinking extracellular matrix components and activating latent TGFβ. This study assessed physiologic pulmonary function and metabolic alterations in the mouse bleomycin model with TG2 genetic deletion.

Netrin-1 feedforward mechanism promotes pancreatic cancer liver metastasis via hepatic stellate cell activation, retinoid, and ELF3 signaling.

The biology of metastatic pancreatic ductal adenocarcinoma (PDAC) is distinct from that of the primary tumor due to changes in cell plasticity governed by a distinct transcriptome. Therapeutic strategies that target this distinct biology are needed. We detect an upregulation of the neuronal axon guidance molecule Netrin-1 in PDAC liver metastases that signals through its dependence receptor (DR), uncoordinated-5b (Unc5b), to facilitate metastasis in vitro and in vivo.

Determinants of experience & satisfaction in telehealth psychiatry during the COVID-19 pandemic for patients & providers.

Introduction: The objective of this study was to characterize the experiences and overall satisfaction of patients and providers with the March 2020 transition to telehealth in a psychiatric setting (telepsychiatry). The study also investigated how socio-demographic and clinical characteristics impact an individual's experiences and satisfaction with telepsychiatry.

Methods: Responses were collected from 604 patients and 154 providers engaged in clinical care at one of three participating Johns Hopkins Medicine outpatient psychiatric clinics between January 2020-March 2021.

Editorial: The Enigma of "Real World" Mental Health Care.

Copeland et al. have analyzed the Great Smoky Mountains Study (GSMS) database to address an important question in health services research: Does the use of mental health services in childhood prevent the later occurrence of mental health disorders in adulthood? Their answer is, somewhat surprisingly, no. As the authors note, the treatment as prevention hypothesis is not only unsupported in their analyses, but there is also evidence of iatrogenic effects on the later development of substance use disorders, particularly among children with behavioral disorders.

Provider perceived barriers and facilitators to integrating routine outcome monitoring into practice in an urban community psychiatry clinic: A mixed-methods quality improvement project.

Background And Aims: Although mental health clinics are under increasing pressure to demonstrate value and routine outcome monitoring (ROM) has become a mandated component of care, providers have been slow to adopt ROM into practice, with some estimating that less than 20% of mental health clinicians use it consistently in the United States. This article explores perceived barriers and facilitators to integrating ROM into practice among clinicians and administrators in a large urban US community psychiatry clinic.

Method: One hundred and thirty-eight clinical and administrative staff were administered an anonymous web-based survey to elicit attitudes towards ROM.

Three Approaches to Understanding and Classifying Mental Disorder: ICD-11, DSM-5, and the National Institute of Mental Health's Research Domain Criteria (RDoC).

The diagnosis of mental disorder initially appears relatively straightforward: Patients present with symptoms or visible signs of illness; health professionals make diagnoses based primarily on these symptoms and signs; and they prescribe medication, psychotherapy, or both, accordingly. However, despite a dramatic expansion of knowledge about mental disorders during the past half century, understanding of their components and processes remains rudimentary. We provide histories and descriptions of three systems with different purposes relevant to understanding and classifying mental disorder.

Child Affected by Parental Relationship Distress.

Objective: A new condition, "child affected by parental relationship distress" (CAPRD), was introduced in the DSM-5. A relational problem, CAPRD is defined in the chapter of the DSM-5 under "Other Conditions That May Be a Focus of Clinical Attention." The purpose of this article is to explain the usefulness of this new terminology.

Feasibility and acceptability of the DSM-5 Field Trial procedures in the Johns Hopkins Community Psychiatry Programs.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) contains criteria for psychiatric diagnoses that reflect advances in the science and conceptualization of mental disorders and address the needs of clinicians. DSM-5 also recommends research on dimensional measures of cross-cutting symptoms and diagnostic severity, which are expected to better capture patients' experiences with mental disorders. Prior to its May 2013 release, the American Psychiatric Association (APA) conducted field trials to examine the feasibility, clinical utility, reliability, and where possible, the validity of proposed DSM-5 diagnostic criteria and dimensional measures.

APIRE Practice Research Network: accomplishments, challenges, and lessons learned.

The Practice Research Network (PRN) was established in 1993 to bridge the gap between the science base and the clinical practice of psychiatry by expanding the generalizability of findings and involving clinicians in the development and conduct of research. It began as a nationwide network of psychiatrists and has evolved to conduct large-scale, clinical and policy research studies using randomly selected samples of psychiatrists from the AMA Physician Masterfile. This paper provides an overview of major PRN initiatives and the impact of these studies.

Treatment of anxiety disorders by psychiatrists from the American Psychiatric Practice Research Network.

Objective: Anxiety disorders are highly prevalent in the United States, and if untreated, result in a number of negative outcomes. This study aimed to investigate psychiatrists' current treatment practices for patients with anxiety disorders in the United States.

Methods: Psychiatrist-reported data from the 1997 and 1999 American Psychiatric Institute for Research and Education Practice Research Network (PRN) Study of Psychiatric Patients and Treatments (SPPT) were examined, focusing on patients diagnosed with anxiety disorders.

Testing DSM-5 in routine clinical practice settings: feasibility and clinical utility.

Objective: This article describes the clinical utility and feasibility of proposed DSM-5 criteria and measures as tested in the DSM-5 Field Trials in Routine Clinical Practice Settings (RCP). METHODS RCP data were collected online for six months (October 2011 to March 2012). Participants included psychiatrists, licensed clinical psychologists, clinical social workers, advanced practice psychiatric-mental health nurses, licensed counselors, and licensed marriage and family therapists.

Using patient-reported measurement to pave the path towards personalized medicine.

Objective: Given the potential and importance of personalized or individualized medicine for health care delivery and its effects on patients' quality of life, a plenary session was devoted to personalized medicine during the 19th Annual Conference of the International Society for Quality of Life Research held in October 2012 in Budapest, Hungary. This paper summarizes the three presentations and discusses their implications for quality-of-life research.

Methods: Reviews of the literature and presentation of empirical studies.

Chronic neuron- and age-selective down-regulation of TNF receptor expression in triple-transgenic Alzheimer disease mice leads to significant modulation of amyloid- and Tau-related pathologies.

Neuroinflammation, through production of proinflammatory molecules and activated glial cells, is implicated in Alzheimer's disease (AD) pathogenesis. One such proinflammatory mediator is tumor necrosis factor α (TNF-α), a multifunctional cytokine produced in excess and associated with amyloid β-driven inflammation and cognitive decline. Long-term global inhibition of TNF receptor type I (TNF-RI) and TNF-RII signaling without cell or stage specificity in triple-transgenic AD mice exacerbates hallmark amyloid and neurofibrillary tangle pathology.

DSM-5 field trials in the United States and Canada, Part I: study design, sampling strategy, implementation, and analytic approaches.

Objective: This article discusses the design,sampling strategy, implementation,and data analytic processes of the DSM-5 Field Trials.

Method: The DSM-5 Field Trials were conducted by using a test-retest reliability design with a stratified sampling approach across six adult and four pediatric sites in the United States and one adult site in Canada. A stratified random sampling approach was used to enhance precision in the estimation of the reliability coefficients.

DSM-5 field trials in the United States and Canada, Part III: development and reliability testing of a cross-cutting symptom assessment for DSM-5.

Objective: The authors sought to document, in adult and pediatric patient populations, the development, descriptive statistics,and test-retest reliability of cross-cutting symptom measures proposed for inclusion in DSM-5.

Method: Data were collected as part of the multisite DSM-5 Field Trials in large academic settings. There were seven sites focusing on adult patients and four sites focusing on child and adolescent patients.

DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses.

Objective: The DSM-5 Field Trials were designed to obtain precise (standard error,0.1) estimates of the intraclass kappa asa measure of the degree to which two clinicians could independently agree on the presence or absence of selected DSM-5 diagnoses when the same patient was interviewed on separate occasions, in clinical settings, and evaluated with usual clinical interview methods.

Method: Eleven academic centers in the United States and Canada were selected,and each was assigned several target diagnoses frequently treated in that setting.

Dimensional approaches to psychiatric diagnosis in DSM-5.

Background: The Diagnostic and Statistical Manual of Mental Disorders is the compendium of disorder listings and diagnostic criteria used by clinicians in the United States and many other countries. The forthcoming fifth edition of the manual (DSM-5) represents an opportunity to not only update diagnostic information in concert with recent advances in the science and practice of psychiatry, but also to more strongly consider the integration of systematically gathered patient self-assessments of symptom severity.

Aims Of The Study: To present information on planned changes to the DSM diagnostic assessment strategies that incorporate patient-reported data.

Evaluation of an AAV2-based rapamycin-regulated glial cell line-derived neurotrophic factor (GDNF) expression vector system.

Effective regulation of transgene product in anatomically circumscribed brain tissue is dependent on the pharmacokinetics of the regulating agent, the kinetics of transcriptional activation and degradation of the transgene product. We evaluated rapamycin-regulated AAV2-GDNF expression in the rat brain (striatum). Regulated (a dual-component system: AAV2-FBZhGDNF + AAV2-TF1Nc) and constitutive (CMV-driven) expression vectors were compared.