Reconceptualizing mental health in cancer survivorship.

Mental health for cancer survivors in both research and clinical applications has strongly adopted a traditional nosological approach, involving the classification of psychopathology into discrete disorders. However, this approach has recently faced considerable criticism due to issues such as high comorbidity and within-disorder symptom heterogeneity across populations. Moreover, there are additional specific issues impacting the validity of traditional approaches in cancer survivorship populations, including the physiological effects of cancer and its treatments. In response, we provide the case for the hierarchical dimensional approach within psycho-oncology, in particular the Hierarchical Taxonomy of Psychopathology (HiTOP). We discuss not only the potential utility of HiTOP to research and clinical applications within psycho-oncology, but also its limitations, and what is required to apply this approach within cancer survivorship.

psudo: Exploring Multi-Channel Biomedical Image Data with Spatially and Perceptually Optimized Pseudocoloring.

Over the past century, multichannel fluorescence imaging has been pivotal in myriad scientific breakthroughs by enabling the spatial visualization of proteins within a biological sample. With the shift to digital methods and visualization software, experts can now flexibly pseudocolor and combine image channels, each corresponding to a different protein, to explore their spatial relationships. We thus propose psudo, an interactive system that allows users to create optimal color palettes for multichannel spatial data. In psudo, a novel optimization method generates palettes that maximize the perceptual differences between channels while mitigating confusing color blending in overlapping channels. We integrate this method into a system that allows users to explore multi-channel image data and compare and evaluate color palettes for their data. An interactive lensing approach provides on-demand feedback on channel overlap and a color confusion metric while giving context to the underlying channel values. Color palettes can be applied globally or, using the lens, to local regions of interest. We evaluate our palette optimization approach using three graphical perception tasks in a crowdsourced user study with 150 participants, showing that users are more accurate at discerning and comparing the underlying data using our approach. Additionally, we showcase psudo in a case study exploring the complex immune responses in cancer tissue data with a biologist.

Is it time to discard the Diagnostic and Statistical Manual of Mental Disorders (DSM) in psycho-oncology?

The conceptual basis of psychopathology within cancer survivorship is critical, as the chosen conceptualisation informs assessment and explanatory models, as well as interventions and supportive care approaches. The validity of a chosen conceptualisation of psychopathology is therefore paramount for ensuring cancer survivors receive high-quality and efficacious care and support that can be iteratively improved via coordinated research efforts. In this paper, we discuss the traditional diagnostic approach to conceptualising psychopathology within cancer care, including the diagnostic system the 'Diagnostic and Statistical Manual of Mental Disorders' (DSM) [1], and the significant issues it presents within cancer survivorship. We detail and discuss how an alternate conceptualisation of psychopathology may enhance both research and practice within psycho-oncology. We ultimately pose, and provide our perspective, on the question "Is it Time to Discard the DSM in Psycho-Oncology?"

Addressing persistent challenges in digital image analysis of cancerous tissues.

The National Cancer Institute (NCI) supports many research programs and consortia, many of which use imaging as a major modality for characterizing cancerous tissue. A trans-consortia Image Analysis Working Group (IAWG) was established in 2019 with a mission to disseminate imaging-related work and foster collaborations. In 2022, the IAWG held a virtual hackathon focused on addressing challenges of analyzing high dimensional datasets from fixed cancerous tissues. Standard image processing techniques have automated feature extraction, but the next generation of imaging data requires more advanced methods to fully utilize the available information. In this perspective, we discuss current limitations of the automated analysis of multiplexed tissue images, the first steps toward deeper understanding of these limitations, what possible solutions have been developed, any new or refined approaches that were developed during the Image Analysis Hackathon 2022, and where further effort is required. The outstanding problems addressed in the hackathon fell into three main themes: 1) challenges to cell type classification and assessment, 2) translation and visual representation of spatial aspects of high dimensional data, and 3) scaling digital image analyses to large (multi-TB) datasets. We describe the rationale for each specific challenge and the progress made toward addressing it during the hackathon. We also suggest areas that would benefit from more focus and offer insight into broader challenges that the community will need to address as new technologies are developed and integrated into the broad range of image-based modalities and analytical resources already in use within the cancer research community.

Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma.

Lymphocytes are key for immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. We used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of lung tumors from a Kras/Trp53-mutant mouse model and human resections. Networks of interacting lymphocytes ("lymphonets") emerged as a distinctive feature of the anti-cancer immune response. Lymphonets nucleated from small T cell clusters and incorporated B cells with increasing size. CXCR3-mediated trafficking modulated lymphonet size and number, but T cell antigen expression directed intratumoral localization. Lymphonets preferentially harbored TCF1+ PD-1+ progenitor CD8+ T cells involved in responses to immune checkpoint blockade (ICB) therapy. Upon treatment of mice with ICB or an antigen-targeted vaccine, lymphonets retained progenitor and gained cytotoxic CD8+ T cell populations, likely via progenitor differentiation. These data show that lymphonets create a spatial environment supportive of CD8+ T cell anti-tumor responses.

Visinity: Visual Spatial Neighborhood Analysis for Multiplexed Tissue Imaging Data.

New highly-multiplexed imaging technologies have enabled the study of tissues in unprecedented detail. These methods are increasingly being applied to understand how cancer cells and immune response change during tumor development, progression, and metastasis, as well as following treatment. Yet, existing analysis approaches focus on investigating small tissue samples on a per-cell basis, not taking into account the spatial proximity of cells, which indicates cell-cell interaction and specific biological processes in the larger cancer microenvironment. We present Visinity, a scalable visual analytics system to analyze cell interaction patterns across cohorts of whole-slide multiplexed tissue images. Our approach is based on a fast regional neighborhood computation, leveraging unsupervised learning to quantify, compare, and group cells by their surrounding cellular neighborhood. These neighborhoods can be visually analyzed in an exploratory and confirmatory workflow. Users can explore spatial patterns present across tissues through a scalable image viewer and coordinated views highlighting the neighborhood composition and spatial arrangements of cells. To verify or refine existing hypotheses, users can query for specific patterns to determine their presence and statistical significance. Findings can be interactively annotated, ranked, and compared in the form of small multiples. In two case studies with biomedical experts, we demonstrate that Visinity can identify common biological processes within a human tonsil and uncover novel white-blood cell networks and immune-tumor interactions.

Brazilian Version of the Level of Personality Functioning Scale-Brief Form 2.0: Evidence of Reliability and Validity / Versão Brasileira da Escala de Nível de Funcionamento da Personalidade - Forma Breve - 2.0: Evidência de Fidedignidade e Validade

Abstract The goal of this research was to investigate the psychometric properties of the Level of Personality Functioning Scale - Brief Form - 2.0 (LPFS-BF-2.0) in Brazilian samples. Therefore, two samples were used in this study, one with 415 and the other with 1,011 Brazilians. Participants completed the Brazilian version of the LPFS-BF-2.0 and other measures of common mental disorder symptoms, suicide risk, the severity of personality pathology, and pathological personality traits. The results indicated that the two-factor model (including self-functioning and interpersonal functioning domains) fits the Brazilian samples better than a one-factor model. The LPFS-BF-2.0 scales indicated adequate reliability coefficients and evidence of convergent validity.

Resumo O objetivo desta pesquisa foi investigar as propriedades psicométricas da Escala de Nível de Funcionamento da Personalidade - Forma Breve - 2.0 (LPFS-BF-2.0) em amostras brasileiras. Assim, duas amostras foram utilizadas, uma com 415 e outra com 1.011 brasileiros. Os participantes responderam a versão brasileira da LPFS-BF-2.0 e outras medidas de sintomas de transtornos mentais comuns, de risco de suicídio, de severidade da patologia da personalidade e de traços patológicos da personalidade. Os resultados indicaram que o modelo de dois fatores (incluindo os fatores de funcionamento do self e interpessoal) ajustou melhor às amostras de brasileiros do que o modelo de um fator. As escalas da LPFSP-BF-2.0 indicaram adequados coeficientes de fidedignidade e evidência de validade convergente.

Study and Detection of Citrus Viroids in Woody Hosts.

Biological indexing is based upon the ability of certain plants, referred to as indicator plants or indicators, to produce specific symptoms when inoculated with a pathogen using mechanical means or grafting. In the case of citrus viroids, clonal indicators are grafted on to vigorous rootstocks such as rough lemon (Citrus × granulata Raf.). The 'Arizona-861-S-1' citron clonal indicator (C. medica L.) can detect and bioamplify all citrus viroids; however, for specific citrus variants of the hop stunt viroid (i.e., CVd-IIb and CVd-IIc), the clonal indicator 'Parson's special # 9' mandarin (C. reticulata Blanco) is preferred. Inoculation techniques and symptom expression are described in detail. Other supporting elements, such as greenhouse conditions and propagation techniques, are also presented.

Scope2Screen: Focus+Context Techniques for Pathology Tumor Assessment in Multivariate Image Data.

Inspection of tissues using a light microscope is the primary method of diagnosing many diseases, notably cancer. Highly multiplexed tissue imaging builds on this foundation, enabling the collection of up to 60 channels of molecular information plus cell and tissue morphology using antibody staining. This provides unique insight into disease biology and promises to help with the design of patient-specific therapies. However, a substantial gap remains with respect to visualizing the resulting multivariate image data and effectively supporting pathology workflows in digital environments on screen. We, therefore, developed Scope2Screen, a scalable software system for focus+context exploration and annotation of whole-slide, high-plex, tissue images. Our approach scales to analyzing 100GB images of 109 or more pixels per channel, containing millions of individual cells. A multidisciplinary team of visualization experts, microscopists, and pathologists identified key image exploration and annotation tasks involving finding, magnifying, quantifying, and organizing regions of interest (ROIs) in an intuitive and cohesive manner. Building on a scope-to-screen metaphor, we present interactive lensing techniques that operate at single-cell and tissue levels. Lenses are equipped with task-specific functionality and descriptive statistics, making it possible to analyze image features, cell types, and spatial arrangements (neighborhoods) across image channels and scales. A fast sliding-window search guides users to regions similar to those under the lens; these regions can be analyzed and considered either separately or as part of a larger image collection. A novel snapshot method enables linked lens configurations and image statistics to be saved, restored, and shared with these regions. We validate our designs with domain experts and apply Scope2Screen in two case studies involving lung and colorectal cancers to discover cancer-relevant image features.

Specific antisocial and borderline personality disorder criteria and general substance use: A twin study.

Antisocial (ASPD) and borderline (BPD) personality disorders (PDs) are associated with increased risk for substance use. They are "specific" risk factors among PDs in that they withstand adjusting for the other PDs, whereas the reverse does not hold. Specificity is a classic sign of causation. This empirical work addresses 3 further problems that can undermine causal inferences in personality and substance-use research: hierarchical nature of etiologic factors in psychiatry, imperfectly operationalized PD criteria, and possible genetic or environmental confounding, as seen in lack of "etiologic continuity." We used exploratory structural equation bifactor modeling and biometric models to mitigate these problems. The participants were Norwegian adult twins of ages 19-36 years (N = 2,801). Criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), PDs were assessed using a structured interview. General substance-use risk was indicated by World Health Organization Composite International Diagnostic Interviewed alcohol use disorder and illicit drug use, and by self-reported regular smoking. A general risk factor for all criteria of both ASPD and BPD was the strongest individual correlate of general substance use and showed etiologic continuity, though just 3 specific PD criteria could predict substance use to the same extent. The findings indicate that a broad latent factor for both ASPD and BPD may be a specific and a genetically and environmentally unconfounded risk factor for substance use. Substance-use treatment research might benefit from attending to transdiagnostic models of ASPD, BPD, and related behavioral disinhibition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Psychometric properties of the Personality Inventory for DSM-5 (PID-5) in brazilian samples / Propriedades psicométricas do Personality Inventory for DSM-5 (PID-5) em amostras brasileiras / Propiedades psicométricas del Personality Inventory for DSM-5 (PID-5) en muestras brasileñas

This study aimed to investigate the psychometric properties of the Personality Inventory for DSM-5 (PID-5) in Brazilian community and clinical samples. This research included 1,210 people, 554 of them with psychopathology indicators. The participants answered the PID-5 and the Self-Reporting Questionnaire, in addition to a sociodemographic and health data questionnaire that included the six items of the suicidality module of the Mini International Neuropsychiatric Interview. The results showed that the 25 facets of the PID-5 had adequate reliability coefficients and evidence of unidimensionality. The instrument's five-factor structure was replicated with high levels of congruence with the representative sample from North America. PID-5 scores were statistically different between clinical and community groups and were positively correlated with measures of suicide risk and psychopathological symptoms. This study presents the psychometric properties of PID-5 and its suitability for use in the Brazilian population (AU).

Este estudo teve como objetivo investigar as propriedades psicométricas do Inventário de Personalidade para o DSM-5 (PID-5) para amostras clínica e comunitária brasileiras. Esta pesquisa incluiu 1.210 pessoas, sendo 554 delas com indicadores de psicopatologia. Os participantes responderam ao PID-5 e ao Self-Reporting Questionnaire, além de um questionário sobre dados sociodemográfico e de saúde que incluía os seis itens do módulo de risco de suicídio Mini International Neuropsychiatric Interview. Os resultados mostraram que as 25 facetas do PID-5 apresentaram coeficientes de confiabilidade adequados e evidências de unidimensionalidade. A estrutura de cinco fatores do instrumento foi replicada com altos níveis de congruência com a amostra representativa da América do Norte. Os escores PID-5 foram estatisticamente diferentes entre os grupos clínicos e comunitários e foram positivamente correlacionados com medidas de risco de suicídio e sintomas psicopatológicos. Este estudo apresenta as propriedades psicométricas do PID-5 e sua adequação para uso na população brasileira (AU).

Este estudio tuvo como objetivo investigar las propiedades psicométricas del Inventario de Personalidad para el DSM-5 (PID-5) en muestras clínicas y comunitarias de Brasil. Esta investigación incluyó a 1.210 personas, 554 de ellas con indicadores de psicopatología. Los participantes respondieron al PID-5 y al Self-Reporting Questionnaire, además de un cuestionario de datos sociodemográficos y de salud que incluía los seis ítems del módulo de suicidio de la Mini Entrevista Neuropsiquiátrica Internacional. Los resultados mostraron que las 25 facetas del PID-5 presentaron coeficientes de confiabilidad adecuados y evidencias de unidimensionalidad. La estructura de cinco factores del instrumento se replicó con altos niveles de congruencia con la muestra representativa de Norteamérica. Las puntuaciones de PID-5 fueron estadísticamente diferentes entre los grupos clínicos y comunitarios, y se correlacionaron positivamente con las medidas de riesgo de suicidio y síntomas psicopatológicos. Este estudio presenta las propiedades psicométricas del PID-5 y su idoneidad para su uso en la población brasileña (AU).

Facetto: Combining Unsupervised and Supervised Learning for Hierarchical Phenotype Analysis in Multi-Channel Image Data.

Facetto is a scalable visual analytics application that is used to discover single-cell phenotypes in high-dimensional multi-channel microscopy images of human tumors and tissues. Such images represent the cutting edge of digital histology and promise to revolutionize how diseases such as cancer are studied, diagnosed, and treated. Highly multiplexed tissue images are complex, comprising 109 or more pixels, 60-plus channels, and millions of individual cells. This makes manual analysis challenging and error-prone. Existing automated approaches are also inadequate, in large part, because they are unable to effectively exploit the deep knowledge of human tissue biology available to anatomic pathologists. To overcome these challenges, Facetto enables a semi-automated analysis of cell types and states. It integrates unsupervised and supervised learning into the image and feature exploration process and offers tools for analytical provenance. Experts can cluster the data to discover new types of cancer and immune cells and use clustering results to train a convolutional neural network that classifies new cells accordingly. Likewise, the output of classifiers can be clustered to discover aggregate patterns and phenotype subsets. We also introduce a new hierarchical approach to keep track of analysis steps and data subsets created by users; this assists in the identification of cell types. Users can build phenotype trees and interact with the resulting hierarchical structures of both high-dimensional feature and image spaces. We report on use-cases in which domain scientists explore various large-scale fluorescence imaging datasets. We demonstrate how Facetto assists users in steering the clustering and classification process, inspecting analysis results, and gaining new scientific insights into cancer biology.

Personality Types and Personality Traits in DSM-5: Do They Really Match? / Tipos e Traços de Personalidade no DSM-5: Eles Realmente Combinam?

Abstract The alternative model of personality disorders introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders provides a diagnostic system that is expected to correspond to the well-known categorical approach of personality disorder diagnoses. The current study aims to improve knowledge about the relationship between pathological personality traits and their corresponding personality types. A Brazilian sample of 1,162 people took part in this study. The results point to some level of continuity between the two models when the variables were treated as dimensional. Contrariwise, there is a lack of strong scientific evidence to justify the maintenance of the categorical approach. We recommend the exclusion of the categorical approach from personality disorder diagnosis systems.

Resumo O modelo alternativo de transtornos da personalidade introduzido na quinta edição do Manual Diagnóstico e Estatístico de Transtornos Mentais oferece um sistema diagnóstico que supostamente deve corresponder ao bem conhecido modelo de diagnóstico categórico dos transtornos da personalidade. O presente estudo tem por objetivo incrementar os conhecimentos sobre a relação entre os traços de personalidade e seus correspondentes tipos de personalidade. Uma amostra brasileira de 1.162 pessoas participou deste estudo. Os resultados indicaram algum nível de continuidade entre os dois modelos quando as variáveis foram consideradas dimensionais. Por outro lado, existe uma falta de evidência científica que justifique a manutenção da abordagem categórica. Recomenda-se a exclusão da abordagem categórica de sistemas diagnósticos de transtornos da personalidade.

A Decline in Propensity Toward Risk Behaviors Among U.S. Adolescents.

PURPOSE: Over the past two decades, substance use, delinquent behaviors, and promiscuous sexual activity have declined substantially among U.S. adolescents. We aimed to determine the extent to which these trends represent declines in a general propensity to engage in risk behaviors (i.e., declines in a latent factor). METHODS: We used Youth Risk Behavior Survey data (1999-2017) (n = 147,800) and examined trends in substance use (e.g., alcohol), delinquency (e.g., fighting), and sexual activity (e.g., number of partners). We conducted two types of analyses stratified by grade (9th/10th vs. 11th/12th) and sex: (1) estimation of year-specific prevalence of each behavior and modeled prevalence changes over time and (2) factor analysis and application of alignment methods to determine changes in the mean of the latent factor over time while correcting for measurement noninvariance. RESULTS: A single factor explained 53% (girls 11th/12th grade) to 62% (boys 9th/10th grade) of the variance in risk behaviors. Average relative annual declines in the prevalence of each behavior-except for weapon carrying-ranged from 1% to 6%. The structure of the latent factor was mostly unchanged over time, with notable exceptions related to differential changes in prevalence for cigarette and cannabis use. Between 1999 and 2017, the mean of the latent factor declined by between .54 and .73 standard deviations. CONCLUSIONS: Results suggest that much of the decline in the prevalence of substance use, delinquent, and sexual behaviors among American youth from 1999 to 2017 reflect an approximately two-thirds standard deviation decline in the mean of a latent risk behavior factor.

Genetic and environmental determinants of population variation in interleukin-6, its soluble receptor and C-reactive protein: insights from identical and fraternal twins.

Interleukin-6 and C-reactive protein are commonly assessed biomarkers linked to illness, obesity, and stressful life events. However, relatively little is known about their heritability. By comparing Caucasian twins from the Midlife in the US project (MIDUS), we estimated the heritability of IL-6, its soluble receptor, and CRP. Based on the hypothesis that adiposity might contribute more to IL-6 than to sIL-6r, we fit heritability models quantifying the extent to which each reflected genetic and environmental factors shared with obesity. Genetic influences on IL-6 and its receptor proved to be distinct. Further, the appearance of a heritable basis for IL-6 was mediated largely via shared paths with obesity. Supporting this conclusion, we confirmed that when unrelated adult controls are carefully matched to twin participants on BMI, age, gender and socioeconomic indices, their IL-6 is similar to the corresponding twins. In contrast, the effect of BMI on CRP was split between shared genetics and environmental influences. In conclusion, IL-6 is strongly affected by factors associated with obesity accounting for its lability and responsiveness to diet, life style and contemporaneous events.

The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment.

BACKGROUND AND AIMS: Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. DESIGN: Physical, sexual and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over 3 years of follow-up, with and without control for other childhood adversities. SETTING: National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). PARTICIPANTS: NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n = 1172) and nicotine dependence (n = 4017). MEASUREMENTS: Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment and other adverse childhood experiences (e.g. parental divorce). FINDINGS: Controlling for demographics only, physical, sexual and emotional abuse and physical neglect predicted 3-year persistence of alcohol dependence [adjusted odds ratio (AOR) = 1.50-2.99; 95% CI = 1.04-4.68] and nicotine dependence (AOR = 1.37-1.74; 95% CI = 1.13-2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AOR = 1.53-3.02; 95% CI = 1.07-4.71) and nicotine persistence (AOR = 1.35-1.72; 95% CI = 1.11-2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AOR = 1.19-1.36; 95% CI = 1.11-1.56). CONCLUSIONS: A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of dependence.

ADHD and the externalizing spectrum: direct comparison of categorical, continuous, and hybrid models of liability in a nationally representative sample.

PURPOSE: Alcohol use disorders, substance use disorders, and antisocial personality disorder share a common externalizing liability, which may also include attention-deficit hyperactivity disorder (ADHD). However, few studies have compared formal quantitative models of externalizing liability, with the aim of delineating the categorical and/or continuous nature of this liability in the community. This study compares categorical, continuous, and hybrid models of externalizing liability. METHOD: Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Seven disorders were modeled: childhood ADHD and lifetime diagnoses of antisocial personality disorder (ASPD), nicotine dependence, alcohol dependence, marijuana dependence, cocaine dependence, and other substance dependence. RESULTS: The continuous latent trait model provided the best fit to the data. Measurement invariance analyses supported the fit of the model across genders, with females displaying a significantly lower probability of experiencing externalizing disorders. Cocaine dependence, marijuana dependence, other substance dependence, alcohol dependence, ASPD, nicotine dependence, and ADHD provided the greatest information, respectively, about the underlying externalizing continuum. CONCLUSIONS: Liability to externalizing disorders is continuous and dimensional in severity. The findings have important implications for the organizational structure of externalizing psychopathology in psychiatric nomenclatures.

CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.

AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR) = 0.65, P = 2.4 × 10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P = 6.7 × 10(-16) , total n = 4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (ß = -0.08, P = 0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.

Personality disorders and the 3-year course of alcohol, drug, and nicotine use disorders.

CONTEXT: Little is known about the role of a broad range of personality disorders in the course of substance use disorder (SUD) and whether these differ by substance. The existing literature focuses mostly on antisocial personality disorder and does not come to clear conclusions. OBJECTIVE: To determine the association between the 10 DSM-IV personality disorders and the persistence of common SUDs in a 3-year prospective study of a national sample. DESIGN: Data were drawn from participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had alcohol dependence (n = 1172), cannabis use disorder (n = 454), or nicotine dependence (n = 4017) at baseline and who were reinterviewed 3 years later. Control variables included demographic characteristics, family history of substance disorders, baseline Axis I disorders and treatment status, and prior SUD duration. Main Outcome Measure  Persistent SUD, defined as meeting full criteria for the relevant SUD throughout the 3-year follow-up period. RESULTS: Persistent SUD was found among 30.1% of participants with alcohol dependence, 30.8% with cannabis use disorder, and 56.6% with nicotine dependence at baseline. Axis I disorders did not have strong or consistent associations with persistent SUD. In contrast, antisocial personality disorder was significantly associated with persistent alcohol, cannabis, and nicotine use disorders (adjusted odds ratios, 2.46-3.51), as was borderline personality disorder (adjusted odds ratios, 2.04-2.78) and schizotypal personality disorder (adjusted odds ratios, 1.65-5.90). Narcissistic, schizoid, and obsessive-compulsive personality disorders were less consistently associated with SUD persistence. CONCLUSIONS: The consistent findings on the association of antisocial, borderline, and schizotypal personality disorders with persistent SUD indicates the importance of these personality disorders in understanding the course of SUD. Future studies should examine dimensional representations of personality disorders and the role of specific components of these disorders, biological and environmental contributors to these relationships, and potential applications of these findings to treatment development.

The emerging link between alcoholism risk and obesity in the United States.

CONTEXT: The prevalence of obesity has risen sharply in the United States in the past few decades. Etiologic links between obesity and substance use disorders have been hypothesized. OBJECTIVE: To determine whether familial risk of alcohol dependence predicts obesity and whether any such association became stronger between the early 1990s and early 2000s. DESIGN: We conducted analyses of the repeated cross-sectional National Longitudinal Alcohol Epidemiologic Survey (1991-1992) and National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002). SETTING: The noninstitutionalized US adult population in 1991-1992 and 2001-2002. PARTICIPANTS: Individuals drawn from population-based, multistage, random samples (N = 39 312 and 39 625). MAIN OUTCOME MEASURE: Obesity, defined as a body mass index (calculated from self-reported data as weight in kilograms divided by height in meters squared) of 30 or higher and predicted from family history of alcoholism and/or problem drinking. RESULTS: In 2001-2002, women with a family history of alcoholism (defined as having a biological parent or sibling with a history of alcoholism or alcohol problems) had 49% higher odds of obesity than those without a family history (odds ratio, 1.48; 95% confidence interval, 1.36-1.61; P < .001), a highly significant increase (P < .001) from the odds ratio of 1.06 (95% confidence interval, 0.97-1.16) estimated for 1991-1992. For men in 2001-2002, the association was significant (odds ratio, 1.26; 95% confidence interval, 1.14-1.38; P < .001) but not as strong as for women. The association and the secular trend for women were robust after adjustment for covariates, including sociodemographic variables, smoking status, alcohol use, alcohol or drug dependence, and major depression. Similar trends were observed for men but did not meet statistical significance criteria after adjustment for covariates. CONCLUSIONS: These results provide epidemiologic support for a link between familial alcoholism risk and obesity in women and possibly in men. This link has emerged in recent years and may result from an interaction between a changing food environment and predisposition to alcoholism and related disorders.