Department of Behavioral Sciences and Social Medicine

: How And Why Weight Stigma Drives The Obesity 'epidemic' And Harms Health; Background: In an era when obesity prevalence is high throughout much of the world, there is a correspondingly pervasive and strong culture of weight stigma. For example, representative studies show that some forms of weight discrimination are more prevalent even than discrimination based on race or ethnicity. Discussion: In this Opinion article, we review compelling evidence that weight stigma is harmful to health, over and above objective body mass index. Weight stigma is prospectively related to heightened mortality and other chronic diseases and conditions. Most ironically, it actually begets heightened risk of obesity through multiple obesogenic pathways. Weight stigma is particularly prevalent and detrimental in healthcare settings, with documented high levels of 'anti-fat' bias in healthcare providers, patients with obesity receiving poorer care and having worse outcomes, and medical students with obesity reporting high levels of alcohol and substance use to cope with internalized weight stigma. In terms of solutions, the most effective and ethical approaches should be aimed at changing the behaviors and attitudes of those who stigmatize, rather than towards the targets of weight stigma. Medical training must address weight bias, training healthcare professionals about how it is perpetuated and on its potentially harmful effects on their patients. Conclusion: Weight stigma is likely to drive weight gain and poor health and thus should be eradicated. This effort can begin by training compassionate and knowledgeable healthcare providers who will deliver better care and ultimately lessen the negative effects of weight stigma., Keywords: mortality, discrimination, body-mass index, Obesity, adults, perceptions, public-health, bias, overweight, physical health, medical-students, Anti-fat attitudes, Discrimination, Health policy, Weight bias, Weight stigma, Publication Note: The publisher’s version of record is available at https://doi.org/10.1186/s12916-018-1116-5

: How and why weight stigma drives the obesity 'epidemic' and harms health.; In an era when obesity prevalence is high throughout much of the world, there is a correspondingly pervasive and strong culture of weight stigma. For example, representative studies show that some forms of weight discrimination are more prevalent even than discrimination based on race or ethnicity. In this Opinion article, we review compelling evidence that weight stigma is harmful to health, over and above objective body mass index. Weight stigma is prospectively related to heightened mortality and other chronic diseases and conditions. Most ironically, it actually begets heightened risk of obesity through multiple obesogenic pathways. Weight stigma is particularly prevalent and detrimental in healthcare settings, with documented high levels of 'anti-fat' bias in healthcare providers, patients with obesity receiving poorer care and having worse outcomes, and medical students with obesity reporting high levels of alcohol and substance use to cope with internalized weight stigma. In terms of solutions, the most effective and ethical approaches should be aimed at changing the behaviors and attitudes of those who stigmatize, rather than towards the targets of weight stigma. Medical training must address weight bias, training healthcare professionals about how it is perpetuated and on its potentially harmful effects on their patients. Weight stigma is likely to drive weight gain and poor health and thus should be eradicated. This effort can begin by training compassionate and knowledgeable healthcare providers who will deliver better care and ultimately lessen the negative effects of weight stigma., Keywords: Anti-fat attitudes, Discrimination, Health policy, Obesity, Weight bias, Weight stigma, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092785.

: Hypothalamic-Pituitary Function in Brain Death; The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord., Keywords: Uniform Determination of Death Act, brain death, diabetes insipidus, hypothalamus, pituitary, Note: Originally published in Journal of Intensive Care Medicine: http://jic.sagepub.com/content/early/2014/03/29/0885066614527410.long, Citation: Nair-Collins M, Northrup J, & Olcese J. (2014). Hypothalamic-pituitary function in brain death: A review. J Intensive Care Med. 2014 Mar 31.

: Implementing Ehealth Interventions For People Living With Hiv

: Impulsivity-Related Traits Are Associated with Higher White Blood Cell Counts; A chronically elevated white blood cell (WBC) count is a risk factor for morbidity and mortality. The present research tests whether facets of impulsivity-impulsiveness, excitement-seeking, self-discipline, and deliberation-are associated with chronically elevated WBC counts. Community-dwelling participants (N = 5,652) from Sardinia, Italy, completed a standard personality questionnaire and provided blood samples concurrently and again 3 years later. Higher scores on impulsivity, in particular impulsiveness and excitement-seeking, were related to higher total WBC counts and higher lymphocyte counts at both time points. Impulsiveness was a predictor of chronic inflammation: for every standard deviation difference in this trait, there was an almost 25% higher risk of elevated WBC counts at both time points (OR = 1.23, 95% CI = 1.10-1.38). These associations were mediated, in part, by smoking and body mass index. The findings demonstrate that links between psychological processes and immunity are not limited to acute stressors; stable personality dispositions are associated with a chronic inflammatory state., Keywords: personality, impulsivity, white blood cells, inflammation, neuroticism, conscientiousness, Note: Originally published online 2011 December 22 in J Behav Med. doi: 10.1007/s10865-011-9390-0, Citation: Sutin AR, Milaneschi Y, Cannas A, Ferrucci L, Uda M, Schlessinger D, Zonderman AB, & Terracciano A. (2012). Impulsivity-related traits are associated with higher white blood cell counts. Journal of Behavioral Medicine, 35(6):616-623.

: Incidence of Diabetes Mellitus and Obesity and the Overlap of Comorbidities in HIV plus Hispanics Initiating Antiretroviral Therapy; Background Cardiovascular disease (CVD) is a leading health threat for HIV+ patients on antiretroviral therapy (ART); cardiometabolic comorbidities are key predictors of risk. Data are limited on incidence of metabolic comorbidities in HIV+ individuals initiating ART in low and middle income countries (LMICs), particularly for Hispanics. We examined incidence of diabetes and obesity in a prospective cohort of those initiating ART in the Dominican Republic. Methods Participants >= 18 years, initiating ART <90 days prior to study enrollment, were examined for incidence of impaired fasting glucose (IFG), diabetes mellitus (DM), overweight, and obesity. Fasting plasma glucose (FPG) 100-125mg/dl defined IFG; FPG >= 126 mg/dl, diagnosis per medical record, or use of hypoglycemic medication defined DM. Overweight and obesity were BMI 25-30 and >= 30kg/m2, respectively. Dyslipidemia was total cholesterol >= 240mg/dl or use of lipid-lowering medication. Framingham risk equation was used to determine ten-year CVD risk at the end of observation. Results Of 153 initiating ART, 8 (6%) had DM and 23 (16%) had IFG at baseline, 6 developed DM (28/1000 person-years follow up [PYFU]) and 46 developed IFG (329/1000 PYFU). At baseline, 24 (18%) were obese and 36 (27%) were overweight, 15 became obese (69/1000 PYFU) and 22 became overweight (163/1000 PYFU). Median observation periods for the diabetes and obesity analyses were 23.5 months and 24.3 months, respectively. Increased CVD risk (>= 10% 10-year Framingham risk score) was present for 13% of the cohort; 79% of the cohort had >= 1 cardiometabolic comorbidity, 48% had >= 2, and 13% had all three. Conclusions In this Hispanic cohort in an LMIC, incidences of IFG/DM and overweight/obesity were similar to or higher than that found in high income countries, and cardiometabolic disorders affected three-quarters of those initiating ART. Care models incorporating cardiovascular risk reduction into HIV treatment programs are needed to prevent CVD-associated mortality in this vulnerable population., Keywords: acute myocardial-infarction, body-mass index, cardiovascular-disease risk, cohort, d-a-d, data-collection, infected patients, metabolic syndrome, prevalence, weight-gain, Publication Note: The publisher’s version of record is available at https://doi.org/10.1371/journal.pone.0160797

: Key Attributes Of Patient Centered Medical Homes Associated With Patient Activation Of Diabetes Patients; Background: Approximately 24 million Americans are living with diabetes. Patient activation among individuals with diabetes is critical to successful diabetes management. The Patient Centered Medical Home (PCMH) model holds promise for increasing patient activation in managing their health. However, what is not well understood is the extent to which individual components of the PCMH model, such as the quality of physician-patient interactions and organizational features of care, contribute to patient activation. This study's objective is to determine the relative importance of the PCMH constructs or domains to patient activation among individuals living with diabetes. Methods: This study is a cross-sectional analysis of 1253 primary care patients surveyed with type II diabetes. The dependent variable, patient activation, was assessed using the Patient Activation Measure (PAM). Independent variables included 7 PCMH domains-organizational access, integration of care, comprehensive knowledge, office staff helpfulness, communication, interpersonal treatment and trust. Ordered logistic regression was performed to determine whether each PCMH domain was independently associated with patient activation, followed by a final ordered logistic regression that included all the PCMH domains in a single adjusted model. Results: Using the full adjusted model, the odds of patients reporting higher activation scores (PAM) were found to be significant in the domains that represented organizational access (OR 1.56, 95% CI 1.31-1.85) and comprehensive knowledge (OR 1.44, 95% CI 1.13-1.85). Conclusions: Many practices have struggled with the challenge to develop fully functional patient-centered medical homes. In an effort to become more patient-centered, this study aimed to address what factors activated diabetic patients to adhere to diabetes management plan. Understanding these factors can help identify PCMH attributes that practices can prioritize and improve upon to assist their patients in improving health outcomes., Keywords: health, validation, primary-care, satisfaction, translation, chronic illness, measure pam13, patients experiences, physician, short-form, Publication Note: The publisher's version of record is available at https://doi.org/10.1186/s12875-017-0704-3

: Loneliness is associated with risk of cognitive impairment in the Survey of Health, Ageing and Retirement in Europe; Objectives: To test whether loneliness is associated with risk of cognitive impairment up to 11 years later in a European sample of middle-aged and older adults. The study examines whether this association is independent of measures of social isolation, depression and other risk factors for cognitive impairment and dementia.Methods: Participants (N = 14,114) from the Survey of Health, Ageing and Retirement in Europe (SHARE) answered a single item on loneliness at baseline and were assessed for cognitive impairment every two-to-three years for 11 years. Participants who scored at least 1.5 standard deviations below the age-graded mean on both a memory recall task and verbal fluency task were classified as impaired. A 3-item measure of loneliness was available for a sample of respondents followed up to 4 years.Results: Feeling lonely was associated with increased risk of incident cognitive impairment (HR = 1.31, 95%CI = 1.19-1.44), after accounting for age, sex, education, and SHARE country strata. The association was robust but reduced in magnitude when controlling for clinical and behavioral risk factors, health-related activity limitations, social isolation, social disengagement and depressive symptoms. The association was not moderated by socio-demographic factors and was also apparent when using the 3-item loneliness scale instead of the single-item measure.Conclusions: These findings expand the extant literature on loneliness and risk of cognitive impairment in older adulthood. Loneliness is one modifiable factor that can be intervened on prior to the development of severe impairment or dementia., Keywords: loneliness, incident cognitive impairment, psycho-social risk factors, social isolation, Publication Note: This is the accepted manuscript, and the version of record can be found at https://www.doi.org/10.1002/gps.5304, Grant Number: NIH/NIA, Grant/Award Numbers: R01AG053297, R21AG057917, R21AG058117

: Macros to Conduct Tests of Multimodality in SAS; The Dip Test of Unimodality and Silverman's Critical Bandwidth Test are two popular tests to determine if an unknown density contains more than one mode. While the tests can be easily run in R, they are not included in SAS software. We provide implementations of the Dip Test and Silverman Test as macros in the SAS software, capitalizing on the capability of SAS to execute R code internally. Descriptions of the macro parameters, installation steps, and sample macro calls are provided, along with an appendix for troubleshooting. We illustrate the use of the macros on data simulated from one or more Gaussian distributions as well as on the famous iris dataset., Keywords: dip test, Silverman's critical bandwidth test, implementation, SAS, software, unimodality, Publication Note: Preprint available from arXiv: https://arxiv.org/abs/1802.00151

: Marijuana use and viral suppression in persons receiving medical care for HIV-infection.; Marijuana use is common among persons living with HIV (PLWH), but studies on its effect on HIV clinical outcomes are limited. We determined the association between marijuana use and HIV viral suppression among PLWH. Data came from five repeated cross-sections (2009-2013) of the Florida Medical Monitoring Project, a population-based sample of PLWH in Florida. Data were obtained via interview and medical record abstraction (MRA). Weighted logistic regression models were used to determine the association between marijuana use (past 12 months) and durable viral suppression (HIV-1 RNA value of ≤ 200 copies/milliliter in all measurements within the past 12 months). Of the 1,902 PLWH receiving antiretroviral therapy, completed an interview, and had a linked MRA, 20% reported marijuana use (13% less than daily and 7% daily use) and 73% achieved durable viral suppression. In multivariable analysis, marijuana use was not significantly associated with durable viral suppression in daily [Adjusted Odds Ratio (AOR): 0.87, 95% confidence interval (CI): 0.58, 1.33] or in less than daily [AOR: 0.83, 95% CI: 0.51, 1.37] users as compared to non-users when adjusting for sociodemographic factors, time since HIV diagnosis, depressive symptoms, alcohol, cigarette and other substance use. In this sample of PLWH receiving medical care in Florida, there was no statistically significant association between marijuana use and viral suppression. However, as the limits of the confidence intervals include effects that may be considered to be clinically important, there is a need for additional evidence from other samples and settings that include more marijuana users., Keywords: HIV, Marijuana, Persons living with HIV (PLWH), Viral suppression, Grant Number: F31 AA024064, F31 DA039810, K23 DA039769, U24 AA022002, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226929.

: Maternal cigarette smoking during pregnancy and the trajectory of externalizing and internalizing symptoms across childhood; Maternal smoking during pregnancy (MSDP) has been associated with symptoms of externalizing (e.g., hyperactivity) and internalizing (e.g., emotional) disorders in childhood. The present research addresses two new questions about the nature of this relation: (1) Do the associations between MSDP and externalizing and internalizing symptoms vary by who reports the symptoms? and (2) Is MSDP associated with changes in symptomatology across childhood? We address these questions with two cohorts from the Longitudinal Study of Australian Children (LSAC). Parents and teachers completed the Strengths and Difficulties Questionnaire up to six times every two years between child ages 4 and 14 in the older cohort (N = 3841) and up to four times between child ages 4 and 10 in the younger cohort (N = 3714); the study children also completed the same questionnaire up to three times starting at age 10. Across the two cohorts, MSDP was associated with more externalizing symptoms as reported by parents, teachers, and self. MSDP was also associated with increases in externalizing symptoms across childhood when teachers assessed the symptoms but not when parents assessed them. Finally, MSDP was not consistently associated with the average level of internalizing symptoms, but it was associated with increases in these symptoms across childhood. The present research indicates a robust association between MSDP and the average level of externalizing symptoms in childhood regardless of who reports the symptoms. It also indicates that whether MSDP is associated with the trajectory of externalizing symptomatology depends on who reports on the symptoms., Keywords: Externalizing behavior, Internalizing behavior, Maternal smoking during pregnancy, Teacher reports, Grant Number: R01 AG053297, R03 AG051960, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647462.

: Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.; Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc., Keywords: GIS, Agriculture, Birth defects, Congenital anomalies, Pesticide exposure, Residential, Grant Number: P30 ES010126, T32ES007018, T32 ES007018, R01 ES020619, R01ES020619, P2C HD050924, P30ES010126, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833532.

: Mediation Analysis of Relationships Between Chronic Inflammation and Quality of Life in Older Adults; Background: This article summarizes exploratory analyses of relationships between chronic inflammation, its physical consequences, and quality of life (QoL). It summarizes key findings from preliminary analyses, and contextualizes these results with extant sociomedical literature to recommend directions for future research. Methods: Cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP) were used to explore these relationships. Inflammation was assessed via the biomarker C-reactive protein (CRP). We examined associations between CRP levels and two different domains of QoL: happiness with life in general and happiness with intimate relationships. We used ordinal logistic regression with companion OLS models and Sobel-Goodman tests to assess potential mediation, and also conducted a variety of sensitivity analyses. Results: Findings suggest that mediation pathways for the overall association between chronic inflammation and QoL may differ markedly across particular outcome constructs. Specifically, it shows mediation potential for the clinical sequelae of chronic inflammation in frameworks using happiness as an outcome measure, but not in those using relationship satisfaction. Disability appears to mediate the effect of inflammation by 27 %; chronic pain appears to exert a similar mediation effect of 21 %. Conclusions: Pain and disability linked to chronic inflammation appear to play a small but significant mediating role in the overall reduction in QoL observed among older adults with biomarker evidence of chronic inflammation. We note that these patterns are best framed as dynamic elements of a complex causal fabric, rather than powerful determinants that override other factors contributing to QoL. Hypotheses for further exploration using longitudinal data from the NSHAP are thus offered, pending availability of Wave III data in future years., Keywords: inflammation, quality of life, elaboration modeling, NSHAP, logistic regression, Preferred Citation: Nowakowski AC1, Graves KY2, Sumerau JE3. Mediation analysis of relationships between chronic inflammation and quality of life in older adults. Health Qual Life Outcomes. 2016: 14(1):46. doi: 10.1186/s12955-016-0452-4.

: Mediation analysis of relationships between chronic inflammation and quality of life in older adults.; This article summarizes exploratory analyses of relationships between chronic inflammation, its physical consequences, and quality of life (QoL). It summarizes key findings from preliminary analyses, and contextualizes these results with extant sociomedical literature to recommend directions for future research. Cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP) were used to explore these relationships. Inflammation was assessed via the biomarker C-reactive protein (CRP). We examined associations between CRP levels and two different domains of QoL: happiness with life in general and happiness with intimate relationships. We used ordinal logistic regression with companion OLS models and Sobel-Goodman tests to assess potential mediation, and also conducted a variety of sensitivity analyses. Findings suggest that mediation pathways for the overall association between chronic inflammation and QoL may differ markedly across particular outcome constructs. Specifically, it shows mediation potential for the clinical sequelae of chronic inflammation in frameworks using happiness as an outcome measure, but not in those using relationship satisfaction. Disability appears to mediate the effect of inflammation by 27 %; chronic pain appears to exert a similar mediation effect of 21 %. Pain and disability linked to chronic inflammation appear to play a small but significant mediating role in the overall reduction in QoL observed among older adults with biomarker evidence of chronic inflammation. We note that these patterns are best framed as dynamic elements of a complex causal fabric, rather than powerful determinants that override other factors contributing to QoL. Hypotheses for further exploration using longitudinal data from the NSHAP are thus offered, pending availability of Wave III data in future years., Keywords: Elaboration modeling, Inflammation, Logistic regression, NSHAP, Quality of life, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802844.

: Medical Residents' and Practicing Physicians' e-Cigarette Knowledge and Patient Screening Activities; The purpose of this study was to compare medical residents and practicing physicians in primary care specialties regarding their knowledge and beliefs about electronic cigarettes (e-cigarettes). We wanted to ascertain whether years removed from medical school had an effect on screening practices, recommendations given to patients, and the types of informational sources utilized. A statewide sample of Florida primary care medical residents (n = 61) and practicing physicians (n = 53) completed either an online or paper survey, measuring patient screening and physician recommendations, beliefs, and knowledge related to e-cigarettes. χ tests of association and linear and logistic regression models were used to assess the differences within- and between-participant groups. Practicing physicians were more likely than medical residents to believe e-cigarettes lower cancer risk in patients who use them as an alternative to cigarettes ( = .0003). Medical residents were more likely to receive information about e-cigarettes from colleagues ( = .0001). No statistically significant differences were observed related to e-cigarette knowledge or patient recommendations. Practicing primary care physicians are accepting both the benefits and costs associated with e-cigarettes, while medical residents in primary care are more reticent. Targeted education concerning the potential health risks and benefits associated with the use of e-cigarettes needs to be included in the current medical education curriculum and medical provider training to improve provider confidence in discussing issues surrounding the use of this product., Keywords: Clinical guidelines, Electronic cigarettes, Medical education, Primary care, Smoking, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266463.

: Meta-analysis of Genome-Wide Association Studies for Extraversion; Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion., Keywords: Common genetic variants, Imputation, Personality, Phenotype harmonization, Polygenic risk, Grant Number: ETM/55, RC2 MH089951, R01 MH061675, R01MH066140, CZB/4/505, K02AA018755, DA019951, R01AA011886, U01HG004438, MH79470, U01 HG004438, U10AA008401, MH59565, R01 MH081802, U01 HG004446, R01 MH066206, MH60870, MH59586, R01 AA009367, AA13320, MH60879, MC_UU_12013/3, U01 MH046276, N01-AG-1-2109, P50 AA011998, R01 AA007728, MH46289, DA02812, K99 HG006265, 104036/Z/14/Z., DA12854, MH59571, AA13321, CZD/16/6, R01 AA011886, P01 CA089392, U01 MH079469, , R01AA009367, R56 DA012854, T32 AA007580, MH66206, HG006265, R01 AA009203, MR/K026992/1, U01 DA024417, 102215, R01DA013240, R01 MH067257, R01 AA013321, AA15416, DA007255, T32 DA007255, R01 MH060870, R01 MH059571, HHSN268200782096C, R01 MH059565, MC_PC_15018, R01 DA024417, U01 HG004422, MH61675, 74882, U01 MH079470, MH46276, AA07728, MH46318, MC_UU_12013/1, R01 MH059587, K02 AA018755, DA024845, MH67257, AA11998, R01 MH066140, MC_UU_12013/4, CZD/16/6/4, MC_PC_U127561128, 076467, R01 DA012854, T32 MH016880, K05 AA000145, R01 MH059586, NIH T32 MH016880, U01 MH046289, K08 DA019951, , R01 AA012502, MH59588, AA07580, R01 DA021336, MH79469, R01 MH059566, DA021336, R01 AA015416, U10 AA008401, HHSN268200782096C, R37 AA007728, U01DA024417, BB/F019394/1, R01 MH059588, U01 MH046318, R21 DA024845, RC2MH089951, R01 DA002812, R00 HG006265, MH59566, R37 DA005147, HHSN271200477451C, HG004422, DK U01-066134, R01 MH060879, MH59587, R01 AA013320, R01 DA013240, R37 AA012502, MH081802, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751159.

: Meta-analysis of Genome-wide Association Studies Identifies Common Variants in CTNNA2 Associated with Excitement-seeking; The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N=7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P=2 × 10(-8)). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed α-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N=5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders., Keywords: genetic variation, polymorphism, single nucleotide, psychomotor agitation, Alpha Catenin, Uncontrolled subjects: Adolescent, Adult, Australia, Baltimore, Estonia, Female, Finland, Genetic Variation, Genome-Wide Association Study, Germany, Humans, Italy, Longitudinal Studies, Male, Middle Aged, Netherlands, Polymorphism, Single Nucleotide, Psychomotor Agitation, Young Adult, alpha Catenin, Note: Originally published in Translational Psychiatry (2011) 1, e49; doi:10.1038/tp.2011.42, Citation: Terracciano A, Esko T, Sutin AR, de Moor MHM, Meirelles O, Zhu G, Tanaka T, Giegling I, Nutile T, Realo A, Allik J, Hansell NK, Wright MJ, Montgomery GW, Willemsen G, Hottenga JJ, Friedl M, Ruggiero D, Sorice R, Sanna S, Cannas A, Raikkonen K, Widen E, Palotie A, Eriksson JG, Cucca F, Krueger RF, Lahti J, Luciano M, Smoller JW, van Duijn CM, Abecasis GR, Boomsma DI, Ciullo M, Costa PT, Ferrucci L, Martin NG, Metspalu A, Rujescu D, Schlessinger D, and Uda M. (2011). Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. Translational Psychiatry (2011) 1, e49; doi:10.1038/tp.2011.42

: Mismatch Between the Educational Pipeline and Public Health Workforce; Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869094.

: My Child Is Islet Autoantibody Positive; To assess parent anxiety in response to genetic and islet autoantibody (IA) testing in children at increased genetic risk for type 1 diabetes followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Parent anxiety about TEDDY children's risk was assessed with the State Anxiety Inventory (SAI). Parents completed the SAI when the child was 3, 6, and 15 months old and annually thereafter. Children were tested for IA every 3 months for 4 years and every 6 months thereafter. Parent SAI scores of 6,799 children followed with IA testing for at least 1 and up to 6 years were examined. At study inception, parents showed high levels of anxiety in response to their child's increased genetic type 1 diabetes risk; mothers were more anxious than fathers, and parents with diabetes in the family were more anxious than parents with no family history. In response to repeated IA-negative (IA-) test results, parent anxiety declined to normal levels. Anxiety increased in parents faced with an IA-positive (IA+) test result. Parents faced with two or more types of IA+ test results showed particularly high levels of anxiety (all < 0.001). Infant genetic screening for type 1 diabetes raises parent anxiety when the child is at increased risk, but anxiety dissipates over time in cases of repeated IA- results. IA+ results heighten parent anxiety, and parents faced with two or more types of IA+ results may experience considerable anxiety for longer periods., Grant Number: U01 DK063821, UC4 DK063863, UL1 TR000064, U01 DK063836, U01 DK063829, U01 DK063865, UC4 DK095300, UC4 DK063861, UC4 DK063829, UC4 DK063821, UC4 DK063836, HHSN267200700014C, U01 DK063861, UL1 TR001427, UC4 DK063865, U01 DK063863, U01 DK063790, UC4 DK106955, UC4 DK100238, UL1 TR001082, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566282.

: Nature and Implementation of Representation in Biological Systems; I defend a theory of mental representation that satisfies naturalistic constraints. Briefly, we begin by distinguishing (i) what makes something a representation from (ii) given that a thing is a representation, what determines what it represents. Representations are states of biological organisms, so we should expect a unified theoretical framework for explaining both what it is to be a representation as well as what it is to be a heart or a kidney. I follow Millikan in explaining (i) in terms of teleofunction, explicated in terms of natural selection. To explain (ii), we begin by recognizing that representational states do not have content, that is, they are neither true nor false except insofar as they both "point to" or "refer" to something, as well as "say" something regarding whatever it is they are about. To distinguish veridical from false representations, there must be a way for these separate aspects to come apart; hence, we explain (ii) by providing independent theories of what I call f-reference and f-predication (the 'f' simply connotes 'fundamental', to distinguish these things from their natural language counterparts). Causal theories of representation typically founder on error, or on what Fodor has called the disjunction problem. Resemblance or isomorphism theories typically founder on what I've called the non-uniqueness problem, which is that isomorphisms and resemblance are practically unconstrained and so representational content cannot be uniquely determined. These traditional problems provide the motivation for my theory, the structural preservation theory, as follows. F-reference, like reference, is a specific, asymmetric relation, as is causation. F-predication, like predication, is a non-specific relation, as predicates typically apply to many things, just as many relational systems can be isomorphic to any given relational system. Putting these observations together, a promising strategy is to explain f-reference via causal history and f-predication via something like isomorphism between relational systems. This dissertation should be conceptualized as having three parts. After motivating and characterizing the problem in chapter 1, the first part is the negative project, where I review and critique Dretske's, Fodor's, and Millikan's theories in chapters 2-4. Second, I construct my theory about the nature of representation in chapter 5 and defend it from objections in chapter 6. In chapters 7-8, which constitute the third and final part, I address the question of how representation is implemented in biological systems. In chapter 7 I argue that single-cell intracortical recordings taken from awake Macaque monkeys performing a cognitive task provide empirical evidence for structural preservation theory, and in chapter 8 I use the empirical results to illustrate, clarify, and refine the theory., Keywords: isormorphism, neural representation, mental content, Note: Dissertation, City University of New York (2009), Citation: Nair-Collins, M. (2009). The nature and implementation of representation in biological systems. Doctoral Dissertation, City University of New York., Submitted Note: A Dissertation submitted to the Graduate Faculty in Philosophy in partial fulfillment of the requirements for the degree of Doctor of Philosophy, The City University of New York., Degree Awarded: Fall Semester, 2009., Date of Defense: November 12, 2009.

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Department of Behavioral Sciences and Social Medicine

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