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ABSTRACT: Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples.
Brain and Cognition 06/2011; 76(1):43-51. · 3.17 Impact Factor
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ABSTRACT: Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known.
Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD).
While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD.
Results may be limited to middle aged males.
The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences.
Journal of affective disorders 04/2011; 132(3):406-12. · 3.76 Impact Factor
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ABSTRACT: Although episodic memory is often conceptualized as consisting of multiple component processes, there is a lack of understanding as to whether these processes are influenced by the same or different genetic determinants. The aim of the present study was to utilize multivariate twin analyses to elucidate the degree to which learning and delayed recall, two critical measures of episodic memory performance, have common or different genetic and environmental influences.
Participants from the Vietnam Era Twin Study of Aging (314 monozygotic twin pairs, 259 dizygotic twin pairs, and 47 unpaired twins) were assessed using the second edition of the California Verbal Learning Test. Mean age at the time of the evaluation was 55.4 years (SD = 2.5).
Model fitting revealed the presence of a higher-order latent factor influencing learning, short- and long-delay free recall, with a heritability of .36. The best-fitting model also indicated specific genetic influences on learning, which accounted for 10% of the overall variance. Given that learning involves the acquisition and retrieval of information, whereas delayed recall involves only retrieval, we conclude that these specific effects are likely to reflect genes that are specific to acquisition processes.
These results demonstrate that even in nonclinical populations, it is possible to differentiate component processes in episodic memory. These different genetic influences may have implications for gene association studies, as well as other genetic studies of cognitive aging and disorders of episodic memory such as Alzheimer's disease or mild cognitive impairment.
Neuropsychology 04/2011; 25(4):488-98. · 3.82 Impact Factor
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ABSTRACT: To determine the incidence of and risk factors for non-melanoma skin cancer (NMSC) in a national cohort of veterans with RA.
We examined skin cancer risk in a cohort of 20 648 patients with RA derived from the Department of Veterans' Affairs (VA) national administrative databases. The cohort was divided into two medication groups: patients treated with non-biologic and TNF-α antagonist DMARDs. We defined skin cancer as the first occurrence of an International Classification of Disease, Version 9, Clinical Modification (ICD-9-CM) code for NMSC after initiation of a DMARD. Outcome risk was described using hazard ratios (HRs) with Cox proportional hazards regression for time-to-event analysis and logistic regression. We performed medical record review to validate the diagnosis of NMSC.
Incidence of NMSC was 18.9 and 12.7 per 1000 patient-years in patients on TNF-α antagonists and non-biologic DMARDs, respectively. Patients on TNF-α antagonists had a higher risk of developing NMSC (HR 1.42; 95% CI 1.24, 1.63). Risk factors for NMSC included older age, male gender, NSAID and glucocorticoid use and a history of prior malignancies. There was substantial agreement between ICD-9-CM diagnosis of NMSC and medical record validation (κ = 0.61).
TNF-α antagonist therapy in veterans with RA may be associated with an increased risk of NMSC, compared with therapy with non-biologic DMARDs. Rheumatologists should carefully screen patients receiving TNF-α antagonists for pre-cancerous skin lesions and skin cancer.
Rheumatology (Oxford, England) 03/2011; 50(8):1431-9. · 4.24 Impact Factor
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ABSTRACT: We explored the comorbidity between panic attacks (PA), whose symptoms can include gastrointestinal discomfort, and gastrointestinal disorders (GD). Structural equation modeling was used to analyze data from 1,874 MZ and 1,498 DZ male-male twin pairs from the Vietnam Era Twin Registry. PA and GD were associated (relative risk for GD = 2). The percentage of liability due to genetic factors was estimated to be 37% for PA and 31% for GD. There was significant correlation between the genetic risk factors for PA and GD (estimated r = .55, 95% CI of 34% to 82%) and no evidence of correlation between the environmental causes of PA and GD. Therefore, PA and GD comorbidity can be explained by overlapping genetic factors and not overlapping environmental factors. Although these data cannot identify a biological pathway for such a shared liability, it suggests the presence of GD may be informative for genetic studies of panic.
Twin Research and Human Genetics 02/2011; 14(1):16-24. · 1.70 Impact Factor
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ABSTRACT: Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-α antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA. A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88-2.43) and TNF-α antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-α antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy. We conclude that patients with RA who are treated with TNF-α antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection.
Medicine 02/2011; 90(2):139-45. · 4.35 Impact Factor
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ABSTRACT: Marriage is considered one of the most important sources of social support that an individual receives as an adult. Although hypotheses have been formulated as to why individuals may dissolve a marriage, the determinants of marital success or failure are still relatively unknown. Behavioral geneticists have found that both marriage and divorce are, in part, genetically influenced. The goal of this research was to determine the degree of shared genetic and environmental variance between the two marital statuses. Participants were 6225 twin pairs from the Vietnam Era Twin Registry. Data were obtained on marital history, and if the individual was no longer married, how the marriage ended. Univariate analyses were performed to determine the extent of genetic and environmental influences each of the marital statues (i.e., marriage and divorce), followed by a novel bivariate analysis to test the shared variance between marriage and divorce. Results from this analysis revealed that the two different marital statuses were influenced by entirely distinct genetic and environmental factors.
Personality and Individual Differences 10/2010; 49(5):473-478. · 1.88 Impact Factor
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ABSTRACT: Psychopathic personality is characterized by interpersonal dominance, impulsivity, sensation seeking, poor planning, and aggressiveness. Studies have shown that the Multidimensional Personality Questionnaire (MPQ) can be used to estimate scores on the fearless-dominant (FD) and the impulsive-antisocial (IA) dimensions of the Psychopathic Personality Inventory (PPI), the best validated self-report measure of psychopathic personality traits. Prior behavior genetic studies reported roughly equal genetic and nonshared environmental influences for both FD and IA, which remained stable from adolescence to young adulthood. However, no prior studies address genetic and environmental influences on these dimensions beyond early adulthood. We utilized the classic twin method to examine genetic and environmental influences on variance in FD and IA in a sample of middle-aged male twins. Biometric modeling indicated that the variance in both factors is best explained by additive genetic and nonshared environmental influences. FD showed roughly equal contributions from genetic and environmental factors, whereas IA showed greater contributions from environmental than genetic factors. Additionally, the small phenotypic correlation between FD and IA was explained entirely by nonshared environmental factors.
Journal of personality disorders 08/2010; 24(4):473-86. · 3.08 Impact Factor
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Leah D Doane,
William S Kremen,
Lindon J Eaves, Seth A Eisen,
Richard Hauger,
Dirk Hellhammer,
Seymour Levine,
Sonia Lupien,
Michael J Lyons,
Sally Mendoza,
Elizabeth Prom-Wormley,
Hong Xian,
Timothy P York,
Carol E Franz,
Kristen C Jacobson
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ABSTRACT: Millions of adults in the United States travel abruptly across time zones each year. Nevertheless, the impact of traveling over relatively short distances (across 3 or fewer time zones) on diurnal patterning of typical physiological response patterns has yet to be studied in a large, epidemiological sample.
The current research focuses on 764 middle-aged men comparing variations in diurnal cortisol regulation based on number of time zones traveled eastward or westward the day before.
Participants provided samples of salivary cortisol at waking, 30-min postwaking, 10 a.m., 3 p.m., and bedtime.
Eastward travel was associated with a steeper salivary cortisol awakening response (p < .01) and lower peak (PEAK) levels of salivary cortisol the next morning (p < .05). Westward travel was associated with lower peak levels of cortisol the next morning (p < .05). Effect sizes for these differences ranged from Cohen's d = .29 to .47. Differences were not present for 2 days in their home environment.
The results provide evidence that traveling across time zones is associated with diurnal cortisol regulation and should be studied further to understand the subsequent impacts on health and well-being in large national samples.
Health Psychology 03/2010; 29(2):117-23. · 3.87 Impact Factor
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ABSTRACT: To seek evidence for the association of bisphosphonate use with diffuse musculoskeletal pain (MSKP) in a large national cohort, controlling for conditions associated with MSKP.
This retrospective cohort study enrolled all US veterans aged 65 years or older with a vertebral or hip fracture who were treated for at least 1 year between October 1, 1998, and September 30, 2006 (N=26,545). All International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes, demographics, and pharmaceutical data were obtained from national databases. A composite end point, based on ICD-9-CM codes compatible with diffuse MSKP, was constructed. The primary outcome was time until MSKP. We performed regression analysis using the Cox proportional hazards model, controlling for age, sex, race, alcoholism, depression, anxiety, smoking, recent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use, rheumatic disease, and comorbidity score.
The univariate regression identified an association of bisphosphonate exposure and MSKP (hazard ratio, 1.22; 95% confidence interval, 1.04-1.44). In the multivariate regression, however, patients prescribed a bisphosphonate were not more likely to be assigned an ICD-9-CM code compatible with diffuse MSKP (hazard ratio, 1.10; 95% confidence interval, 0.93-1.30). Consistent with prior studies, we found that female sex, depression, anxiety, comorbidity score, and the presence of a rheumatic disease were all associated with a greater risk of a diagnosis of diffuse MSKP. There was no demonstrable association with statin exposure.
Bisphosphonate use was not associated with a statistically higher rate of MSKP in this cohort. Individual patients may rarely report MSKP while taking bisphosphonates; however, for our studied cohort, incident MSKP does not appear to explain bisphosphonate discontinuation rates.
Mayo Clinic Proceedings 03/2010; 85(4):341-8. · 5.70 Impact Factor
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ABSTRACT: Hereditary influences account for a substantial proportion of the variance in many cognitive abilities. However, there is increasing recognition that the relative importance of genetic and environmental influences may vary across different socioeconomic levels. The overall goal of the present study was to examine whether parental education has a moderating effect on genetic and environmental influences of general cognitive ability in early adulthood (age 19.6 +/- 1.5). Participants were 5,955 male twins from the Vietnam Era Twin (VET) Registry. Significant effects of parental education on mean level of general cognitive ability scores were found, but a model without moderating effects of parental education on genetic or environmental influences on cognitive scores proved to be the best fitting model. Some, but not all, previous studies have found significant moderating effects; however, no consistent pattern emerged that could account for between-study differences regarding moderating effects on genetic and environmental influences.
Behavior Genetics 03/2010; 40(4):438-46. · 2.52 Impact Factor
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ABSTRACT: To determine if depression contributes to incident heart disease after accounting for genetic, behavioral, and medical factors associated with both conditions.
We used a prospective twin study with a 12-year follow-up. In 1992, lifetime diagnosis of depression was assessed in 1159 male-male twins and merged with longitudinal health data from the Vietnam Era Twin Registry Study of Aging. Incident heart disease was defined as having myocardial infarction, heart surgery, or angina at 12-year follow-up when twins were 55.4 years (standard deviation, 2.5 years) of age. Risks for heart disease were computed in a logistic regression model that included comparing twins at different levels of phenotypic expression of depression and varying levels of genetic vulnerability at the same time adjusting for pertinent covariates.
After adjusting for sociodemographics, co-occurring psychopathology, smoking, obesity, diabetes, hypertension, and social isolation, twins at high genetic risk and exposed to depression remained at greater risk of developing ischemic heart disease (IHD) (odds ratio, 2.55; 95% confidence interval, 1.44-4.49) compared with those at low genetic risk and without phenotypic expression of depression. Odds ratios suggest that twins at genetic liability but without phenotypic expression were at risk of IHD, but the effect was not statistically significant.
A history of depression is a risk factor for incident heart disease after adjusting for numerous covariates. Twins with both high genetic vulnerability and phenotypic expression of depression were at greatest risk of IHD. Trends suggest the genetic contribution to IHD that overlaps with depression may partly explain this association, but studies in larger samples are warranted.
Psychosomatic Medicine 02/2010; 72(4):370-5. · 3.97 Impact Factor
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William S Kremen,
Robert C O'Brien,
Matthew S Panizzon,
Elizabeth Prom-Wormley,
Lindon J Eaves, Seth A Eisen,
Lisa T Eyler,
Richard L Hauger,
Christine Fennema-Notestine,
Bruce Fischl, [......],
Terry L Jernigan,
Sonia J Lupien,
Michael J Lyons,
Sally P Mendoza,
Michael C Neale,
Larry J Seidman,
Heidi W Thermenos,
Ming T Tsuang,
Anders M Dale,
Carol E Franz
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ABSTRACT: Although glucocorticoid receptors are highly expressed in the prefrontal cortex, the hippocampus remains the predominant focus in the literature examining relationships between cortisol and brain. We examined phenotypic and genetic associations of cortisol levels with the thickness of prefrontal and anterior cingulate cortex regions, and with hippocampal volume in a sample of 388 middle-aged male twins who were 51-59 years old. Small but significant negative phenotypic associations were found between cortisol levels and the thickness of left dorsolateral (superior frontal gyrus, left rostral middle frontal gyrus) and ventrolateral (pars opercularis, pars triangularis, pars orbitalis) prefrontal regions, and right dorsolateral (superior frontal gyrus) and medial orbital frontal cortex. Most of the associations remained significant after adjusting for general cognitive ability, cardiovascular risk factors, and depression. Bivariate genetic analyses suggested that some of the associations were primarily accounted for by shared genetic influences; that is, some of the genes that tend to result in increased cortisol levels also tend to result in reduced prefrontal cortical thickness. Aging has been associated with reduced efficiency of hypothalamic-pituitary-adrenal function, frontal lobe shrinkage, and increases in health problems, but our present data do not allow us to determine the direction of effects. Moreover, the degree or the direction of the observed associations and the extent of their shared genetic underpinnings may well change as these individuals age. Longitudinal assessments are underway to elucidate the direction of the associations and the genetic underpinnings of longitudinal phenotypes for changes in cortisol and brain morphology.
NeuroImage 02/2010; 53(3):1093-102. · 5.89 Impact Factor
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Lars M Rimol,
Matthew S Panizzon,
Christine Fennema-Notestine,
Lisa T Eyler,
Bruce Fischl,
Carol E Franz,
Donald J Hagler,
Michael J Lyons,
Michael C Neale,
Jennifer Pacheco,
Michele E Perry,
J Eric Schmitt,
Michael D Grant,
Larry J Seidman,
Heidi W Thermenos,
Ming T Tsuang, Seth A Eisen,
William S Kremen,
Anders M Dale
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ABSTRACT: Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the patterning of those genetic influences, i.e., whether the same genes influence structure throughout the brain or whether there are regionally specific sets of genes.
We mapped the heritability of cortical thickness throughout the brain using three-dimensional structural magnetic resonance imaging in 404 middle-aged male twins. To assess the amount of genetic overlap between regions, we then mapped genetic correlations between three selected seed points and all other points comprising the continuous cortical surface.
There was considerable regional variability in the magnitude of genetic influences on cortical thickness. The primary visual (V1) seed point had strong genetic correlations with posterior sensory and motor areas. The anterior temporal seed point had strong genetic correlations with anterior frontal regions but not with V1. The middle frontal seed point had strong genetic correlations with inferior parietal regions.
These results provide strong evidence of regionally specific patterns rather than a single, global genetic factor. The patterns are largely consistent with a division between primary and association cortex, as well as broadly defined patterns of brain gene expression, neuroanatomical connectivity, and brain maturation trajectories, but no single explanation appears to be sufficient. The patterns do not conform to traditionally defined brain structure boundaries. This approach can serve as a step toward identifying novel phenotypes for genetic association studies of psychiatric disorders and normal and pathological cognitive aging.
Biological psychiatry 12/2009; 67(5):493-9. · 8.93 Impact Factor
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William S Kremen,
Elizabeth Prom-Wormley,
Matthew S Panizzon,
Lisa T Eyler,
Bruce Fischl,
Michael C Neale,
Carol E Franz,
Michael J Lyons,
Jennifer Pacheco,
Michele E Perry,
Allison Stevens,
J Eric Schmitt,
Michael D Grant,
Larry J Seidman,
Heidi W Thermenos,
Ming T Tsuang, Seth A Eisen,
Anders M Dale,
Christine Fennema-Notestine
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ABSTRACT: The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00-0.75) as compared with subcortical and ventricular ROIs (0.48-0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.
NeuroImage 09/2009; 49(2):1213-23. · 5.89 Impact Factor
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Michael J Lyons,
Timothy P York,
Carol E Franz,
Michael D Grant,
Lindon J Eaves,
Kristen C Jacobson,
K Warner Schaie,
Matthew S Panizzon,
Corwin Boake,
Hong Xian,
Rosemary Toomey, Seth A Eisen,
William S Kremen
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ABSTRACT: Previous research has demonstrated stability of cognitive ability and marked heritability during adulthood, but questions remain about the extent to which genetic factors account for this stability. We conducted a 35-year longitudinal assessment of general cognitive ability using the Armed Forces Qualification Test administered to 7,232 male twins in early adulthood and readministered to a subset of 1,237 twins during late middle age. The proportion of variance in cognitive functioning explained by genetic factors was .49 in young adulthood and .57 in late middle age. The correlation between the two administrations was .74 with a genetic correlation of 1.0, indicating that the same genetic influences operated at both times. Genetic factors were primarily responsible for stability, and nonshared environmental factors were primarily responsible for change. The genetic factors influencing cognition may change across other eras, but the same genetic influences are operating from early adulthood to late middle age.
Psychological Science 09/2009; 20(9):1146-52. · 4.43 Impact Factor
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ABSTRACT: Many U.S. Gulf War-era veterans complained of poor cognition following the war. This study assessed neuropsychological functioning in veterans 10 years after the war through objective tests. 2189 Gulf War-era veterans (1061 deployed, 1128 non-deployed) were examined at 1 of 16 U.S. Veterans Affairs medical centers. Outcomes included neuropsychological domains derived from factor analysis and individual test scores. Deployed veterans performed significantly worse than non-deployed veterans on 2 of 8 factors (motor speed & sustained attention, analysis not corrected for multiple comparisons) and on 4 of 27 individual test variables (Trails A & B, California Verbal Learning Test-List B, and Continuous Performance Test sensitivity, with only Trails B surviving Bonferroni correction). Within deployed veterans, Khamisiyah exposure was negatively correlated with motor speed after controlling for emotional distress. Depressive symptoms and self-reported exposure to toxicants were independently and significantly associated with worse sustained attention. Other factors were also associated with self-reported exposures. The findings were not a result of differential effort across groups. Gulf War deployment is associated with subtle declines of motor speed and sustained attention, despite overall intact neuropsychological functioning. Evidence suggests that toxicant exposures influence both these functions, and depressive symptoms also influence attention.
Journal of the International Neuropsychological Society 07/2009; 15(5):717-29. · 2.76 Impact Factor
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ABSTRACT: Herpes zoster occurs more commonly in patients taking immunosuppressive medications, although the risk associated with different medications is poorly understood.
We conducted a retrospective cohort study involving 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster.
The incidence of herpes zoster was 9.96 episodes per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (P < .001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (hazard ratio, 0.62) and adalimumab (hazard ratio, 0.53) were associated with a lower risk of herpes zoster. There was excellent agreement between the International Classification of Diseases, Version 9, Clinical Modification diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92).
Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs' national administrative databases can be used to study rare adverse drug events.
Clinical Infectious Diseases 05/2009; 48(10):1364-71. · 9.15 Impact Factor
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ABSTRACT: Treatment studies suggest that gambling-related irrational beliefs and attitudes (i.e., cognitive distortions (CDs)) contribute to the risk for problem gambling behavior. In a community sample of men, we investigated the associations among lifetime gambling-related CDs, psychiatric disorders other than pathological gambling , and problem gambling severity. Subjects were 1354 members of the Vietnam Era Twin Registry. Problem gambling and gambling-related CDs were derived from a 2002 interview using the National Opinion Research Center DSM-IV Screen for Gambling Problems (NODS). Exploratory factor analysis was performed with the 12 CD items to identify an underlying construct. Generalized linear models were computed to test for associations among CDs, psychiatric disorders other than pathological gambling, and gambling problem severity. Co-twin control analyses of monozygotic twin pairs discordant for problem gambling severity adjusted for genetic and shared environmental influences. Twelve CD items related to one underlying CD construct. After adjustment for lifetime psychiatric disorders, pathological gambling symptoms were positively associated with higher CD scores. Pathological gambling symptoms remained significantly associated with CD scores after controlling for genetic and shared environmental influence. These results provide empirical support for an association between gambling-related CDs and gambling problem severity, even after controlling for genetic and shared environmental influences and non-pathological gambling psychiatric disorders. Public health messages and therapeutic interventions that reinforce the randomness of gambling and draw attention to distorted thinking may prevent the development of problem gambling and improve treatment outcomes.
Psychiatry Research 10/2008; 160(3):300-7. · 2.52 Impact Factor
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ABSTRACT: To compute the common and specific genetic and environmental contributions to nicotine dependence (ND) alcohol dependence (AD) and cannabis dependence (CD).
Twin model.
Data from 1874 monozygotic and 1498 dizygotic twin pair members of the Vietnam Era Twin Registry were obtained via telephone administration of a structured psychiatric interview in 1992.
Data to derive life-time diagnoses of DSM-III-R ND, AD and CD were obtained via telephone administration of the Diagnostic Interview Schedule.
The best-fitting model allowed for additive genetic contributions and unique environmental influences that were common to all three phenotypes. Risks for ND and AD were also due to genetic and unique environmental influences specific to each drug. A specific shared environmental factor contributed to CD.
These results suggest that the life-time co-occurrence of ND, AD and CD is due to common and specific genetic factors as well as unique environmental influences, and vulnerability for CD is also due to shared environmental factors that do not contribute to ND and AD. The majority of genetic variance is shared across drugs and the majority of unique environmental influences are drug-specific in these middle-aged men. Because differences between models allowing for specific genetic versus shared environment were small, we are most confident in concluding that there are specific familial contributions-either additive genetic or shared environment-to CD.
Addiction 09/2008; 103(8):1391-8. · 4.31 Impact Factor