Medicine and Health Sciences Commons^™

Cocktail-Party Listening And Cognitive Abilities Show Strong Pleiotropy, Samuel R. Mathias, Emma M. Knowles, Josephine Mollon, Peter T. Fox, Rene L. Olvera, Juan M. Peralta, Satish Kumar, Harald H. H. Goring, Ravi Duggirala, Joanne E. Curran, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

Introduction: The cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors. Here, we estimated the degree to which these genetic factors overlapped with those influencing cognitive abilities.

Methods: We measured SRTs and hearing thresholds (HTs) in 493 listeners, who ranged in age from 18 to 91 years old. The same individuals completed a cognitive test …

An Opportunity For Primary Prevention Research In Psychotic Disorders, Elliot S. Gershon, S. Hong Lee, Xuan Zhou, John A. Sweeney, Carol Tamminga, Godfrey A. Pearlson, Brett A. Clementz, Matcheri S. Keshavan, Ney Alliey-Rodriguez, Matthew Hudgens-Haney

School of Medicine Publications and Presentations

An opportunity has opened for research into primary prevention of psychotic disorders, based on progress in endophenotypes, genetics, and genomics. Primary prevention requires reliable prediction of susceptibility before any symptoms are present. We studied a battery of measures where published data supports abnormalities of these measurements prior to appearance of initial psychosis symptoms. These neurobiological and behavioral measurements included cognition, eye movement tracking, Event Related Potentials, and polygenic risk scores. They generated an acceptably precise separation of healthy controls from outpatients with a psychotic disorder.

Methods

The Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) measured this battery …

Impact Of Polygenic Risk For Coronary Artery Disease And Cardiovascular Medication Burden On Cognitive Impairment In Psychotic Disorders, Lusi Zhang, Scot Kristian Hill, Bin Guo, Baolin Wu, Ney Alliey-Rodriguez, Seenae Eum, Paulo Lizano, Elena I. Ivleva, James L. Reilly, Richard S. E. Keefe

School of Medicine Publications and Presentations

Background: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established.

Methods: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e-8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to …

Neuroimaging Association Scores: Reliability And Validity Of Aggregate Measures Of Brain Structural Features Linked To Mental Disorders In Youth, Luiza Kvitko Axelrud, André Rafael Simioni, Daniel Samuel Pine, Anderson M. Winkler, Pedro Mario Pan, João Ricardo Sato, André Zugman, Nadine Parker, Felipe Picon, Andrea Jackowski

School of Medicine Publications and Presentations

In genetics, aggregation of many loci with small effect sizes into a single score improved prediction. Nevertheless, studies applying easily replicable weighted scores to neuroimaging data are lacking. Our aim was to assess the reliability and validity of the Neuroimaging Association Score (NAS), which combines information from structural brain features previously linked to mental disorders. Participants were 726 youth (aged 6–14) from two cities in Brazil who underwent MRI and psychopathology assessment at baseline and 387 at 3-year follow-up. Results were replicated in two samples: IMAGEN (n = 1627) and the Healthy Brain Network (n = 843). NAS …

Genetic Overlap Profiles Of Cognitive Ability In Psychotic And Affective Illnesses: A Multisite Study Of Multiplex Pedigrees, Emma Knowles, Juan M. Peralta, Laura Almasy, Vishwajit Nimgaonkar, Francis J. Mcmahon, Pippa Thomson, Samuel R. Mathias, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

Background: Cognitive impairment is a key feature of psychiatric illness, making cognition an important tool for exploring of the genetics of illness risk. It remains unclear which measures should be prioritized in pleiotropy-guided research. Here, we generate profiles of genetic overlap between psychotic and affective disorders and cognitive measures in Caucasian and Hispanic groups.

Methods: Data were from 4 samples of extended pedigrees (N = 3046). Coefficient of relationship analyses were used to estimate genetic overlap between illness risk and cognitive ability. Results were meta-analyzed.

Results: Psychosis was characterized by cognitive impairments on all measures with a generalized profile of …

Genetic Influences On Externalizing Psychopathology Overlap With Cognitive Functioning And Show Developmental Variation, Josephine Mollon, Emma E. M. Knowles, Samuel R. Mathias, Amanda Rodrigue, Tyler M. Moore, Monica E. Calkins, Ruben C. Gur, Juan M. Peralta, Daniel J. Weiner, John Blangero, Laura Almasy

School of Medicine Publications and Presentations

Background: Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.

Methods: Using data from 9,421 individuals aged 8-21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with …

Associations Of Cannabis Use Disorder With Cognition, Brain Structure, And Brain Function In African Americans, Marinka M. G. Koenis, Joke Durnez, Amanda Rodrigue, Samuel R. Mathias, Aaron F. Alexander-Bloch, Jennifer Barrett, Gaelle E. Doucet, Sophia Frangou, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross-sectional community sample of 205 African Americans (age 18–70) we tested for associations of cannabis use disorder (CUD, n = 57) with multi-domain cognitive measures and structural, diffusion, and resting state brain-imaging phenotypes. Post hoc model evidence was computed with Bayes factors (BF) and posterior probabilities of association (PPA) to account for multiple testing. General cognitive functioning, verbal intelligence, verbal memory, working memory, and motor speed were …

A Qtl On Chromosome 3q23 Influences Processing Speed In Humans, Emma E. M. Knowles, Samuel R. Mathias, Josephine Mollon, Amanda Rodrigue, Marinka M. G. Koenis, Thomas D. Dyer, Harald H. H. Goring, Joanne E. Curran, Rene L. Olvera, Ravindranath Duggirala, Laura Almasy, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

Processing speed is a psychological construct that refers to the speed with which an individual can perform any cognitive operation. Processing speed correlates strongly with general cognitive ability, declines sharply with age, and is impaired across a number of neurological and psychiatric disorders. Thus, identifying genes that influence processing speed will likely improve understanding of the genetics of intelligence, biological aging, and the etiologies of numerous disorders. Previous genetics studies of processing speed have relied on simple phenotypes (e.g., mean reaction time) derived from single tasks. This strategy assumes, erroneously, that processing speed is a unitary construct. In the present …

Associations Between Self-Reported Sleep Quality And White Matter In Community-Dwelling Older Adults: A Prospective Cohort Study, Claire E. Sexton, Enikő Zsoldos, Nicola Filippini, Ludovica Griffanti, Anderson M. Winkler, Abda Mahmood, Charlotte L. Allan, Anya Topiwala, Simon D. Kyle, Kai Spiegelhalder

School of Medicine Publications and Presentations

Both sleep disturbances and decline in white matter microstructure are commonly observed in ageing populations, as well as in age-related psychiatric and neurological illnesses. A relationship between sleep and white matter microstructure may underlie such relationships, but few imaging studies have directly examined this hypothesis. In a study of 448 community-dwelling members of the Whitehall II Imaging Sub-Study aged between 60 and 82 years (90 female, mean age 69.2 ± 5.1 years), we used the magnetic resonance imaging technique diffusion tensor imaging to examine the relationship between self-reported sleep quality and white matter microstructure. Poor sleep quality at the time …

Discovering Schizophrenia Endophenotypes In Randomly Ascertained Pedigrees, David C. Glahn, Jeff T. Williams, Joanne E. Curran, Harald H. H. Goring, Thomas D. Dyer, Anderson M. Winkler, Rene L. Olvera, Ravi Duggirala, Laura Almasy, John Blangero

School of Medicine Publications and Presentations

Background

Although case-control approaches are beginning to disentangle schizophrenia’s complex polygenic burden, other methods will likely be necessary to fully identify and characterize risk genes. Endophenotypes, traits genetically correlated with an illness, can help characterize the impact of risk genes by providing genetically relevant traits that are more tractable than the behavioral symptoms that classify mental illness. Here we present an analytic approach for discovering and empirically validating endophenotypes in extended pedigrees with very few affected individuals. Our approach indexes each family member’s risk as a function of shared genetic kinship with an affected individual, often referred to as the …

[Cognitive Impairment And Associated Factors In Older Adults In Mexico], Silvia Mejía-Arango, Alejandro Miguel-Jaimes, Antonio Villa, Liliana Ruiz-Arregui, Luis Miguel Gutiérrez-Robledo

School of Medicine Publications and Presentations

OBJECTIVE: To determine the prevalence of cognitive impairment in the elderly and its relation with sociodemographic and health factors in the Mexican population.

MATERIAL AND METHODS: From the first wave data of the National Aging and Health Study, collected in 2001 in Mexico, subjects 65 years or older and who had completed a cognitive assessment were selected. Subjects were classified according to two groups: with and without cognitive impairment, based on the cutoff point corresponding to the 10th percentile of the total cognitive assessment score, adjusted for age and educational level. All subjects with cognitive impairment that also had difficulty …