Seth A Eisen

United States Department of Veterans Affairs, Bedford, Massachusetts, United States

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Publications (162)729.42 Total impact

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    ABSTRACT: Objective To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). Patients and Methods A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. Results After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. Conclusion Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.
    Mayo Clinic Proceedings 01/2014; 89(1):43–51. · 5.79 Impact Factor
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    ABSTRACT: Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrences. Bivariate models investigated the magnitudes and correlations of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence, and stimulant abuse/dependence. Computer-assisted telephone interviews in the community. Participants were 7,869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry. Lifetime DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence, and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule. All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic (genetic correlation rA=0.22; 95%CI:0.10-0.34) and non-shared environmental components (environmental correlation rE=0.24; 95%CI:0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA=0.32; 95%CI:0.05-1.0; rE=0.36; 95%CI:0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA=0.58; 95%CI:0.45-0.73). Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using "hard" drugs like cocaine. The greater contribution of environmental factors to the co-occurrences between problem/pathological gambling and "softer" forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders.
    Addiction 11/2013; · 4.58 Impact Factor
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    ABSTRACT: The authors assessed changes in the health status of US 1991 Gulf War-era veterans from a 1995 baseline survey to a 2005 follow-up survey, using repeated measurement data from 5,469 deployed Gulf War veterans and 3,353 nondeployed Gulf War-era veterans who participated in both surveys. Prevalence differences in health status between the 2 surveys were estimated for adverse health indices and chronic diseases for each veteran group. Persistence risk ratios and incidence risk ratios were calculated after adjustment for demographic and military service characteristics through Mantel-Haenszel stratified analysis. At 10-year follow-up, deployed veterans were more likely to report persistent poor health, as measured by the health indices (functional impairment, limitation of activities, repeated clinic visits, recurrent hospitalizations, perception of health as fair or poor, chronic fatigue syndrome-like illness, and posttraumatic stress disorder), than nondeployed veterans. Additionally, deployed veterans were more likely to experience new onset of adverse health (as measured by the indices) and certain chronic diseases than were nondeployed veterans. During the 10-year period from 1995 to 2005, the health of deployed veterans worsened in comparison with nondeployed veterans because of a higher rate of new onset of various health outcomes and greater persistence of previously reported adverse health on the indices.
    American journal of epidemiology 07/2011; 174(7):761-8. · 5.59 Impact Factor
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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. · 2.82 Impact Factor
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    ABSTRACT: To determine whether early adult cognitive ability is a risk factor for depressive symptoms in midlife and how genetic and environmental influences explain the association and to examine cross-sectional relationships between depressive symptoms and specific cognitive abilities at midlife. A 35-year longitudinal and cross-sectional twin study of cognitive aging. Large multicenter study in the United States. One thousand two hundred thirty-seven male twins aged 51 to 60 years. At the age of 20 years and midlife, participants completed the same version of a general cognitive ability test (Armed Forces Qualification Test [AFQT]). Midlife testing included an extensive neurocognitive protocol assessing processing speed, verbal memory, visual-spatial memory, working memory, executive function, and visual-spatial ability. Participants completed the Center for Epidemiologic Studies Depression Scale before cognitive testing and provided health and life style information during a medical history interview. Lower age 20 AFQT scores predicted higher levels of depressive symptoms at age 55 years (r = -0.16,p <0.001). In bivariate twin modeling, 77% of the correlation between early cognitive ability and midlife depressive symptoms was due to shared genetic influences. Controlling for current age, age 20 AFQT, and nonindependence ofobservations, depressive symptoms were associated with worse midlife AFQT scores and poorer performance in all cognitive domains except verbal memory. Results suggest that low cognitive ability is a risk factor for depressive symptoms; this association is partly due to shared genetic influences. Crosssectional analyses indicate that the association between depressive symptoms and performance is not linked to specific cognitive domains.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 06/2011; 19(6):559-70. · 3.35 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. · 3.58 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. · 1.64 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: The effect of TNF-α blockade on the risk of cardiovascular outcomes and long-term survival in patients with rheumatoid arthritis (RA) is not known. We assembled a cohort of 20,811 (75,329 person-years) U.S. veterans who were diagnosed with RA between October 1998 and September 2005, and who were treated with a disease-modifying anti-rheumatic drug (DMARD). Cox survival models were built to examine the effect of TNF-α antagonists on the risk of a composite endpoint of cardiovascular outcomes defined as the occurrence of atherosclerotic heart disease, congestive heart failure, peripheral artery disease, or cerebrovascular disease, and on the risk of death. Treatment with TNF-α antagonists was not associated with a significant effect on the composite endpoint of cardiovascular outcomes. When each outcome was examined separately, the use TNF-α antagonists was not associated with an increased risk of atherosclerotic heart disease, congestive heart failure, or peripheral artery disease, but it was associated with decreased risk of cerebrovascular disease (hazard ratio [HR] = 0.83; confidence interval [CI] = 0.70-0.98). The use of TNF-α antagonists did not affect the risk of death (HR = 0.99; CI = 0.87-1.14). In subgroup analyses, the use TNF-α antagonists was associated with a reduced risk of cardiovascular outcomes (HR = 0.90, CI = 0.83-0.98) in patients younger than the median age of our cohort (63 years). The use TNF-α antagonists was not associated with a change in the risk of death in any other subgroup. These results show that the risk of cardiovascular events and survival in patients who receive TNF-α antagonists is not different than those who receive other DMARDs.
    Translational research : the journal of laboratory and clinical medicine. 01/2011; 157(1):10-8.
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    ABSTRACT: The effect of rate of decline of kidney function on risk for death is not well understood. Using the Department of Veterans Affairs national databases, we retrospectively studied a cohort of 4171 patients who had rheumatoid arthritis and early stage 3 chronic kidney disease (CKD; estimated GFR 45 to 60 ml/min) and followed them longitudinally to characterize predictors of disease progression and the effect of rate of kidney function decline on mortality. After a median of 2.6 years, 1604 (38%) maintained stable kidney function; 426 (10%), 1147 (28%), and 994 (24%) experienced mild, moderate, and severe progression of CKD, respectively (defined as estimated GFR decline of 0 to 1, 1 to 4, and >4 ml/min per yr). Peripheral artery disease predicted moderate progression of CKD progression. Black race, hypertension, diabetes, cardiovascular disease, and peripheral artery disease predicted severe progression of CKD. After a median of 5.7 years, patients with severe progression had a significantly increased risk for mortality (hazard ratio 1.54; 95% confidence interval 1.30 to 1.82) compared with those with mild progression; patients with moderate progression exhibited a similar trend (hazard ratio 1.10; 95% confidence interval 0.98 to 1.30). Our results demonstrate an independent and graded association between the rate of kidney function decline and mortality. Incorporating the rate of decline into the definition of CKD may transform a static definition into a dynamic one that more accurately describes the potential consequences of the disease for an individual.
    Journal of the American Society of Nephrology 11/2010; 21(11):1961-9. · 8.99 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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    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. · 2.61 Impact Factor
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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. · 3.95 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. · 5.79 Impact Factor
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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):1093-1102. · 6.25 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. · 4.08 Impact Factor
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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

Publication Stats

7k Citations
729.42 Total Impact Points

Institutions

  • 2011
    • United States Department of Veterans Affairs
      Bedford, Massachusetts, United States
  • 2005–2011
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, CA, United States
    • Yale University
      • • Child Study Center
      • • Department of Psychiatry
      New Haven, CT, United States
  • 1990–2011
    • Washington University in St. Louis
      • • Department of Psychiatry
      • • Department of Medicine
      San Luis, Missouri, United States
  • 2010
    • Rosalind Franklin University of Medicine and Science
      • Psychology
      North Chicago, IL, United States
  • 1998–2010
    • University of Washington Seattle
      • • Division of General Internal Medicine
      • • Department of Medicine
      Seattle, WA, United States
  • 1995–2010
    • Boston University
      • Department of Psychology
      Boston, MA, United States
  • 2008
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
  • 2005–2008
    • Harvard University
      • Department of Society, Human Development, and Health
      Cambridge, MA, United States
  • 2007
    • Washington DC VA Medical Center
      Washington, Washington, D.C., United States
    • Virginia Commonwealth University
      • Virginia Institute for Psychiatric and Behavioral Genetics
      Richmond, Virginia, United States
  • 1997–2007
    • Saint Louis University
      • College for Public Health & Social Justice
      Saint Louis, MI, United States
  • 1996–2007
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 2004
    • San Francisco VA Medical Center
      San Francisco, California, United States
    • Williams College
      • Department of Psychology
      Williamstown, MA, United States
  • 2003
    • National Center for PTSD
      Washington, Washington, D.C., United States
    • Harvard Medical School
      • Department of Psychiatry
      Boston, MA, United States
  • 2002
    • Columbia University
      • Department of Epidemiology
      New York City, NY, United States
  • 1993–2002
    • University of Massachusetts Boston
      • Department of Psychology
      Boston, MA, United States
  • 2001
    • University of Missouri
      • Department of Psychological Sciences
      Columbia, MO, United States
  • 2000
    • Edward Hines, Jr. VA Hospital
      Hines, Oregon, United States
  • 1990–1999
    • University of Illinois at Chicago
      • • Division of Epidemiology and Biostatistics
      • • School of Public Health
      Chicago, IL, United States