Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Diagnostic Value of Software-Based Image Fusion of Computed Tomography and F18-FDG PET Scans in Patients with Malignant Lymphoma

Aim. The purpose of this study was to evaluate the accuracy of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET), computed tomography (CT), and software-based image fusion of both modalities in the imaging of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). Methods. 77 patients with NHL (n = 58) or HD (n = 19) underwent a FDG PET scan, a contrast-enhanced CT, and a subsequent digital image fusion during initial staging or followup. 109 examinations of each modality were evaluated and compared to each other. Conventional staging procedures, other imaging techniques, laboratory screening, and follow-up data constituted the reference standard for comparison with image fusion. Sensitivity and specificity were calculated for CT and PET separately. Results. Sensitivity and specificity for detecting malignant lymphoma were 90% and 76% for CT and 94% and 91% for PET, respectively. A lymph node region-based analysis (comprising 14 defined anatomical regions) revealed a sensitivity of 81% and a specificity of 97% for CT and 96% and 99% for FDG PET, respectively. Only three of 109 image fusion findings needed further evaluation (false positive). Conclusion. Digital fusion of PET and CT improves the accuracy of staging, restaging, and therapy monitoring in patients with malignant lymphoma and may reduce the need for invasive diagnostic procedures

The diagnosis of mental disorders: the problem of reification

A pressing need for interrater reliability in the diagnosis of mental disorders emerged during the mid-twentieth century, prompted in part by the development of diverse new treatments. The Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition answered this need by introducing operationalized diagnostic criteria that were field-tested for interrater reliability. Unfortunately, the focus on reliability came at a time when the scientific understanding of mental disorders was embryonic and could not yield valid disease definitions. Based on accreting problems with the current DSM-fourth edition (DSM-IV) classification, it is apparent that validity will not be achieved simply by refining criteria for existing disorders or by the addition of new disorders. Yet DSM-IV diagnostic criteria dominate thinking about mental disorders in clinical practice, research, treatment development, and law. As a result, the modernDSMsystem, intended to create a shared language, also creates epistemic blinders that impede progress toward valid diagnoses. Insights that are beginning to emerge from psychology, neuroscience, and genetics suggest possible strategies for moving forward

Eating disorders: from twin studies to candidate genes and beyond

Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way

Patterns of substance use across the first year of college and associated risk factors

Starting college is a major life transition. This study aims to characterize patterns of substance use across a variety of substances across the first year of college and identify associated factors. We used data from the first cohort (N = 2056, 1240 females) of the “Spit for Science” sample, a study of incoming freshmen at a large urban university. Latent transition analysis was applied to alcohol, tobacco, cannabis, and other illicit drug uses measured at the beginning of the fall semester and midway through the spring semester. Covariates across multiple domains – including personality, drinking motivations and expectancy, high school delinquency, peer deviance, stressful events, and symptoms of depression and anxiety – were included to predict the patterns of substance use and transitions between patterns across the first year. At both the fall and spring semesters, we identified three subgroups of participants with patterns of substance use characterized as: (1) use of all four substances; (2) alcohol, tobacco, and cannabis use; and (3) overall low substance use. Patterns of substance use were highly stable across the first year of college: most students maintained their class membership from fall to spring, with just 7% of participants in the initial low substance users transitioning to spring alcohol, tobacco, and cannabis users. Most of the included covariates were predictive of the initial pattern of use, but covariates related to experiences across the first year of college were more predictive of the transition from the low to alcohol, tobacco, and cannabis user groups. Our results suggest that while there is an overall increase in alcohol use across all students, college students largely maintain their patterns of substance use across the first year. Risk factors experienced during the first year may be effective targets for preventing increases in substance use

The role of osteoanabolic agents in the management of patients with osteoporosis

Reducing fracture risk is the objective of osteoporosis treatment. Bone-forming osteoporosis drugs increase bone mass, restore bone microarchitecture, and reduce fracture risk more effectively than oral bisphosphonates, providing strong justification for the use of these agents as the initial therapy or after anti-remodeling agents in patients at very high risk of fracture. At the end of a 12-to-24-month course of osteoanabolic therapy, transitioning to a potent anti-remodeling agent maintains and enhances the treatment benefit. This review describes the clinical applications of osteoanabolic therapy for osteoporosis

Intermediate stable states in substance use

Many people across the world use potentially addictive legal and illegal substances, but evidence suggests that not all use leads to heavy use and dependence, as some substances are used moderately for long periods of time. Here, we empirically examine, the stability of and transitions between three substance use states: zero-use, moderate use, and heavy use. We investigate two large datasets from the US and the Netherlands on yearly usage and change of alcohol, nicotine, and cannabis. Results, which we make available through an extensive interactive tool, suggests that there are stable moderate use states, even after meeting criteria for a positive diagnosis of substance abuse or dependency, for both alcohol and cannabis use. Moderate use of tobacco, however, was rare. We discuss implications of recognizing three states rather than two states as a modeling target, in which the moderate use state can both act as an intervention target or as a gateway between zero use and heavy use

The possibility of evidence-based psychiatry: depression as a case

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the strengths and weaknesses of research onto the causality of relationship between diagnosis and therapy of major depressive disorder and suggest what could be done to strengthen eventual claims on causality. Four obstacles for a rational evidence-based psychiatry were recognised. First, current classification systems are scientifically nonfalsifiable. Second, cerebral processes are—at least to some extent—nondeterministic, i.e. they are random, stochastic and/or chaotic. Third, the vague or lack of relationship between therapeutic regimens and suspected pathogenesis. Fourth, the inadequacy of tools to diagnose and delineate a functional disorder. We suggest a strategy to identify diagnostic prototypes that are characterised by a limited number of parameters (symptoms, markers and other characteristics). A prototypical diagnosis that may either support or reject particular elements of current diagnostic systems. Nevertheless, one faces the possibility that psychiatry will remain a relatively weak evidence-based medical discipline

Prevalência de depressão e fatores associados em homens

El objetivo del presente estudio fue evaluar la prevalencia de depresión, detectar el riesgo suicida e identificar los factores sociodemográficos y personales asociados a este trastorno. La muestra no aleatorizada estuvo conformada por 1525 hombres colombianos con edades entre 18 y 83 años procedentes de 22 departamentos y de distintos niveles educativos. Para evaluar la depresión se usó el Cuestionario de Depresión para Hombres (Álvarez y Londoño, 2012); para evaluar la comorbilidad con ansiedad se usó la Escala de Ansiedad HADS (Zigmond y Snaith, 1983) y el IMAFE (Lara, 1991); y para recolectar información acerca de los factores personales y sociodemográficos se usó una ficha de registro. Se analizaron los datos para calcular la prevalencia de corte, el riesgo suicida, la comorbilidad a través del uso del paquete estadístico SPSS. Se concluye que la prevalencia real reportada y el riesgo suicida en la población estudiada son más altos que los detectados usando un instrumento no sensible al género.O objetivo deste estudo foi avaliar a prevalência de depressão, detectar o risco suicida e identificar os fatores sociodemográficos e pessoais associados com esse transtorno. A amostra não aleatorizada foi conformada por 1525 homens colombianos com idade entre 18 e 83 anos, procedentes de 22 estados e de diferentes níveis de escolaridade. Para avaliar a depressão, foi utilizado o Teste de Depressão para Homens (Álvarez e Londoño, 2012); para avaliar a comorbilidade com ansiedade, usou-se a Escala Hospitalar de Ansiedade e Depressão (Hads – Zigmond e Snaith, 1983) e o Inventário de Masculinidade e Feminilidade (Imafe – Lara, 1991); para coletar informação sobre os fatores pessoais e sociodemográficos, empregou-se um formulário de registro. Analisaram-se os dados para calcular a prevalência de corte, o risco suicida, a comorbilidade por meio do uso do SPSS. Concluise que a prevalência real relatada e o risco de suicídio na população estudada são mais altos do que os detectados usando um instrumento não sensível ao gênero.This epidemiologic study aimed to evaluate the prevalence of depression, the suicide risk and the demographic and personal factors associated with depression severity in men. The non-randomized sample of participants was formed by 1525 Colombian men aged 18 to 83 years old, from 22 departments and different educational levels. The instruments used to evaluate the above factors were the Men’s Depression Questionnaire (Alvarez and Londoño, 2012), the Anxiety Scale HADS (Zigmond y Snaith, 1983) and the IMAFE (Lara 1991), and in order to collect data about personal and socio-demographic factors, a registration card was used. Data were analyzed to calculate the prevalence, suicide risk and comorbidity with anxiety through the use of SPSS. It was concluded that the prevalence of depression and suicide risk in the population object of study is higher than the one identified in previous studies when a non- gender sensitive questionnaire was used

Do different depression phenotypes have different risks for recurrent coronary heart disease?

Although research has consistently established that depression and elevated depressive symptoms are associated with an increased risk of coronary heart disease (CHD) recurrence and mortality, clinical trials have failed to show that conventional depression interventions offset this risk. As depression is a complex and heterogeneous syndrome, we believe that examining simpler, or intermediary, phenotypes rather than one complex phenotype may allow better identification of those at particular risk of CHD recurrence and mortality. This approach may further contribute to the development of specific depression treatments that would improve medical outcomes. Although there are many possible intermediary phenotypes (IPs), specifiers and dimensions of depression, we will focus on only two when considering the relation between depression and risk of CHD recurrence and mortality: Incident Depression and Anhedonic Depression. Future research on IPs of depression is needed to clarify which are associated with the greatest risk for CHD recurrence and mortality and which, if any, are benign. Theoretical advances in depression phenotyping may also help elucidate the behavioural and biological mechanisms underlying the increased risk of CHD among patients with specific depression phenotypes. Finally, tests of depression interventions may be guided by this new theoretical approach