Shun-Chiao Chang

Rheumatoid Arthritis and Mortality Among Women During 36 Years of Prospective Follow-Up: Results From the Nurses’ Health Study

To evaluate rheumatoid arthritis (RA) and mortality risk among women followed prospectively in the Nurses’ Health Study (NHS).

Oxytocin receptor (OXTR) is not associated with optimism in the Nurses' Health Study.

The oxytocin system is implicated in complex social behavior such as socioemotional functioning, social recognition and bonding, and in modulating biological responses to stress.1,2 The oxytocin receptor (OXTR) gene encodes the OXTR; a G-protein-coupled receptor that mediates the effects of the neurohormone oxytocin. 3,4 Prior studies have reported associations between an intronic single-nucleotide polymorphism (rs53576) of OXTR and various stress-related and psychological traits.4,5 Most recently, Saphire-Bernstein et al6 reported that rs53576 A allele carriage conferred lower optimism relative to G homozygotes, among 344 men and women aged 18–36 years of various ethnicities. We sought to replicate the association between OXTR rs53576 and optimism in 1229 women from the Nurses’ Health Study (NHS). n nThe NHS was established in 1976 when 121 700 women registered as nurses aged 30–55 years from 11 US states completed a mailed questionnaire on medical history and lifestyle characteristics.7 Every 2 years, follow-up questionnaires are sent. The 2004 and 2008 questionnaires included information on antidepressant use and the revised life orientation test,8 the same dispositional optimism measure used in the Saphire-Bernstein et al.6 study. We generated five different optimism scores to provide a thorough investigation of the previously reported association. Year-specific optimism scores were derived by taking the mean of all non-missing items in 2004 (α =0.77) and also in 2008 (α =0.75). Individuals with >2 items missing were excluded (up to 8% of analytic sample). Using both assessments, an overall mean optimism score was also derived, as were two subscale scores reflecting an ‘optimistic’ or ‘pessimistic’ outlook.8 Genotypes for the current analysis were available from two case-control nested genome-wide association studies, initially designed to assess kidney stone disease and glaucoma (total n= 1294).9,10 Samples were genotyped for OXTR rs53576 at the Broad Center for Genotyping and Analysis using the Illumina 610Q or 660Q array (Illumina, San Diego, CA, USA). Genotyping success rate for rs53576 was > 98%.9,10 Principal components analyses using genome-wide data were conducted to assess self-reported race. Genetically inferred non-Caucasian samples were too few (<3% of analytic sample) for meaningful analysis and therefore excluded. n nThe 2004 and 2008 optimism scores were moderately correlated (r = 0.65) in the 1229 women with complete genetic and phenotype data (2004 mean age = 71.3 years, s.d. = 6.7). Overall optimism scores ranged from 1.33 to 4.25 (overall mean = 4.13, s.d. = 0.68). Frequencies (%) of the GG, GA and AA genotypes were 491 (40%), 559 (45%) and 179 (15%), respectively, and did not depart from Hardy–Weinberg equilibrium (P = 0.33). The A allele frequency was 38% in NHS versus 28% among white participants (n = 87) in the Saphire-Bernstein et al.6 study. n nTable 1 indicates no significant differences in means across genotypes for any optimism scores (all PADD > 0.35). Optimism scores also did not differ between G homozygotes and A carriers (all PDOM > 0.17). Linear regression models adjusting for age, genotype platform, and case-control status yielded no significant association between rs53576 and any optimism score, regardless of genetic model (all P > 0.16). The NHS sample had substantial power ( > 99%) to detect the effect size reported previously: β = −0.168 under a dominant model.6 n n n nTable 1 n nMean (s.d.) optimism scores by OXTR genotype n n n nUnlike our sample, Saphire-Bernstein et al.’s6 sample consisted of men and women recruited for a stress and coping study, was relatively young (mean age 21) and had mixed ethnic ancestry (for example, 36% Asian). However, although the frequency of the G allele and mean optimism scores differed somewhat across ethnic and gender groups in the Saphire-Bernstein et al.6 study, the pattern of associations did not. Recognizing other differences between the two samples, we conducted several sensitivity analyses (Table 1), considering effects stratified by age or education, excluding women reporting antidepressant use, or with disease (that is, kidney stone or glaucoma). Associations between rs53576 and optimism were null in all analyses. We were limited in power to restrict analysis to even younger women. However, a formal test for OXTR–age interaction was marginally significant (P = 0.10), suggesting age may be an important modifier for future exploration. n nIn summary, we did not replicate the association between rs53576 and optimism in our sample of Caucasian women. Our findings do not exclude a possible role for OXTR in psychosocial resources. The link between rs53576 and optimism may be applicable to a population with characteristics similar to individuals in Saphire-Bernstein et al’s6 study. However, our findings suggest caution is warranted when considering the association between OXTR and optimism, and additional research is needed to determine the generalizability of the results reported by Saphire-Bernstein et al.6

Risk factors for late-life depression: A prospective cohort study among older women.

Depression prevention requires identifying key risk contributors. Prior studies have identified several factors related to late-life depression but have seldom addressed factors jointly or in dose-response fashion. This study aimed to examine a wide range of potential predisposing factors and to estimate individual and joint contributions to risk of late-life depression in women. A total of 21,728 women aged ≥65years, without prior depression, in the Nurses Health Study conducted in the United States were followed from 2000 to 2010. Demographic, social, lifestyle/behavioral and health variables were selected a priori from the literature or previous findings in this cohort. Depression was defined as physician/clinician-diagnosed depression, regular antidepressant use, or the presence of severe depressive symptoms. During 10-year follow-up, 3945 incident cases were identified. After simultaneous multivariable-adjustment, multiple factors in the domains of social stress (lower self-rated societal position and high volume of caregiving to disabled/ill relatives), unfavorable lifestyle (smoking, physical inactivity, heavy or binge drinking), and poor physical health (multiple comorbidity burden, excessive sleep, difficulty falling/staying asleep, bodily pain, and physical/functional limitation or disability) were significantly associated with higher depression risk; many featured dose-response relationships. Sensitivity analyses that excluded outcomes within 2years yielded similar estimates. The total population attributable fraction for all factors was 55.5%. Physical/functional limitation accounted for one-quarter of population attributable fraction, followed by problematic sleep, inadequate exercise, and pain (combining for one-third of population attributable fraction). Efforts to remediate or prevent these factors may contribute to an efficient strategy for late-life depression prevention in women.

Associations of Smoking and Age With Inflammatory Joint Signs Among Unaffected First-Degree Relatives of Rheumatoid Arthritis Patients: Results From Studies of the Etiology of Rheumatoid Arthritis.

To examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs in a cohort of first‐degree relatives (FDRs) of RA patients.

Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses’ Health Study Cohorts

Moderate alcohol consumption has antiinflammatory properties and is associated with reduced cardiovascular disease and rheumatoid arthritis risks. We investigated the association between alcohol consumption and systemic lupus erythematosus (SLE) risk among women followed in the Nurses’ Health Study (NHS) cohorts.

Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women

To conduct the first longitudinal study examining whether trauma exposure and posttraumatic stress disorder (PTSD) are associated with increased risk of incident systemic lupus erythematosus (SLE) in a civilian cohort.

Smoking behavior changes in the early rheumatoid arthritis period and risk of mortality during 36 years of prospective follow-up

To investigate whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality.

Weight Change During the Early Rheumatoid Arthritis Period and Risk of Subsequent Mortality in Women With Rheumatoid Arthritis and Matched Comparators

To investigate whether weight change during the early rheumatoid arthritis (RA) period is associated with subsequent mortality and to evaluate whether there is an RA‐specific effect.

Racial Variation in Depression Risk Factors and Symptom Trajectories among Older Women

OBJECTIVEnTo assess racial variation in depression risk factors and symptom trajectories among older women.nnnMETHODSnUsing Nurses Health Study data, participants (29,483 non-Hispanic white and 288 black women) aged 60 years or older, free of depression in 2000, were followed until 2012. Data on race and risk factors, selected a priori, were obtained from biennial questionnaires. Incident depression was defined as depression diagnosis, antidepressant use, or presence of severe depressive symptoms. Group-based trajectories of depressive symptoms were determined using latent variable modeling approaches.nnnRESULTSnBlack participants had lower risk (hazard ratio: 0.76; 95% confidence interval: 0.57-0.99) of incident late-life depression compared with whites. Although blacks had higher prevalence than whites of some risk factors at study baseline, distributions of major contributors to late-life depression risk (low exercise, sleep difficulty, physical/functional limitation, pain) were comparable. There was evidence of effect modification by race for relations of region of birth (Southern birthplace), smoking, and medical comorbidity to depression risk; however, wide confidence intervals occurred among blacks because of smaller sample size. Four trajectories were identified: minimal symptoms-stable (58.3%), mild symptoms-worsening (31.4%), subthreshold symptoms-worsening (4.8%), and subthreshold symptoms-improving (5.5%). Probabilities of trajectory types were similar for blacks and whites.nnnCONCLUSIONnAlthough overall trajectories of late-life depressive symptoms were comparable by race, there was racial variation in depression risk estimates associated with less-studied factors, such as U.S. region of birth. Future work may address unmeasured health and resilience determinants that may underlie observed findings and that could inform clinical assessment of late-life depression risk factors.

Prospective study of chronotype and incident depression among middle- and older-aged women in the Nurses’ Health Study II

BACKGROUNDnPrior cross-sectional studies have suggested that being a late chronotype is associated with depression and depressive symptoms, but prospective data are lacking.nnnMETHODSnWe examined the association between chronotype and incident depression (defined as self-reported physician/clinician-diagnosed depression or antidepressant medication use) in 32,470 female participants of the Nurses Health Study II cohort who self-reported their chronotype (early, intermediate or late) and were free of depression at baseline in 2009 (average age: 55u202fyrs). Women updated their depression status on biennial questionnaires in 2011 and 2013. We used multivariable (MV)-adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for incident depression across chronotype categories (i.e., early, intermediate, and late chronotypes).nnnRESULTSnAcross a follow-up period of 4 years, we observed 2,581 cases of incident depression in this cohort. Compared to intermediate chronotypes, early chronotypes had a modestly lower risk of depression after MV adjustment (MVHRu202f=u202f0.88, 95%CIu202f=u202f0.81-0.96), whereas late chronotypes had a similar risk of 1.06 (95%CIu202f=u202f0.93-1.20); the overall trend across chronotype categories was statistically significant (ptrend<0.01). Results were similar when we restricted analyses to women who reported average sleep durations (7-8u202fh/day) and no history of rotating night shift work at baseline.nnnCONCLUSIONSnOur results suggest that chronotype may influence the risk of depression in middle-to older-aged women. Additional studies are needed to confirm these findings and examine roles of both environmental and genetic factors to further our understanding of the role of chronotype in the etiology of mood disorders.