A simple, rapid, interpretable, actionable and implementable digital PCR based mortality index.

Mortality assessments are conducted for both civil and commercial purposes. Recent advances in epigenetics have resulted in DNA methylation tools to assess risk and aid in this task. However, widely available array-based algorithms are not readily translatable into clinical tools and do not provide a good foundation for clinical recommendations. Further, recent work shows evidence of heritability and possible racial bias in these indices. Using a publicly available array data set, the Framingham Heart Study (FHS), we develop and test a five-locus mortality-risk algorithm using only previously validated methylation biomarkers that have been shown to be free of racial bias, and that provide specific assessments of smoking, alcohol consumption, diabetes and heart disease. We show that a model using age, sex and methylation measurements at these five loci outperforms the 513 probe Levine index and approximates the predictive power of the 1030 probe GrimAge index. We then show each of the five loci in our algorithm can be assessed using a more powerful, reference-free digital PCR approach, further demonstrating that it is readily clinically translatable. Finally, we show the loci do not reflect ethnically specific variation. We conclude that this algorithm is a simple, yet powerful tool for assessing mortality risk. We further suggest that the output from this or similarly derived algorithms using either array or digital PCR can be used to provide powerful feedback to patients, guide recommendations for additional medical assessments, and help monitor the effect of public health prevention interventions.

Association between depression and mortality in older adults: the Cardiovascular Health Study.

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.

Marital therapy: a viable treatment for depression and marital discord.

Thirty-six maritally discordant couples with depressed wives were randomly assigned to marital therapy, cognitive therapy, or a waiting-list control condition. The women given marital or cognitive therapy showed significant and clinically meaningful reductions in their depression. The women given marital therapy showed greater increases in marital satisfaction than did those given cognitive therapy or no therapy; these differences were maintained at 1-year follow-up. These findings suggest that marital therapy may be the most effective and appropriate treatment for clinically significant marital discord with coexisting clinically significant depression.

Disease status in African American single mothers with HIV: the role of depressive symptoms.

The association between depressive symptoms and 2 measures of HIV disease status in 73 African American single mothers was examined. Hierarchical multiple regression analyses revealed that clinician-rated depressive symptoms predicted subjective, but not objective, parameters of disease status 12 to 14 months later. More symptoms of depression at the 1st assessment predicted an increase in physical complaints over the course of the study. Results suggest that researchers and clinicians interested in enhancing quality of life among African American single mothers with HIV infection, an understudied population within the HIV-AIDS literature, should consider both subjective and objective measures of the disease.

Marital therapy in the treatment of depression: toward a third generation of therapy and research.

Two generations of outcome research demonstrate the potential efficacy of marital therapy in the treatment of depression. After reviewing treatment outcome studies on marital therapy for depression, we examine basic research linking aspects of the marital relationship to depressive symptoms. In doing so, we highlight a number of theoretical perspectives and research findings that can inform work with couples in which one spouse is depressed. Finally, we identify potential innovations that may lead to a third generation of marital interventions for depression and several avenues of inquiry for a third generation of outcome research on marital therapy for depression.

Marital distress, depression, and attributions: is the marital distress-attribution association an artifact of depression?

We examined whether the association between marital distress and attributions is an artifact of depression. Study 1 showed that the attributions of 40 wives recruited from the community accounted for variance in their marital satisfaction after the effects of depression had been taken into account. Study 2 compared the attributions of 20 clinically depressed and maritally distressed wives (respondents to an advertisement offering therapy for depression and marital problems), 20 nondepressed but distressed wives (clients seeking marital therapy at a clinic), and a control group of 20 nondepressed and nondistressed wives (respondents to an advertisement for participants in a research project). The first two groups did not differ in attributions, but the attributions of both groups differed from those of the control group. Both studies therefore suggest that the association between attributions and marital satisfaction is not due to depression.

Attributions and behavior in functional and dysfunctional marriages.

The study examined whether spouses' attributions for partner behavior are related to their own behavior by assessing their attributions and observing the problem-solving discussions of couples in which (a) neither spouse was depressed or maritally distressed, (b) the wife was depressed and both spouses were maritally distressed, and (c) the wife was not depressed and both spouses were maritally distressed. To the extent they made maladaptive attributions, wives displayed less positive behavior and more negative behavior. Husbands' attributions and behavior were unrelated, and associations between attributions and behavior were not moderated by marital distress and depression. These results highlight the need to clarify how partner behavior contributes to the attributions spouses make and to reexamine interventions designed to modify attributions in marital therapy.

Life events, relationship quality, and depression: an investigation of judgment discontinuity in vivo.

Relationships among stressful life events, negative affect, and judged quality of intimate relationships were explored. Three studies and a mini-meta-analysis revealed that as negative life events increased, judgments of close relationships gradually became less favorable, jumped back toward positivity, and then, again, gradually became less favorable. The same methods of analysis revealed a relationship between negative life events and negative affect with no evidence of significant discontinuities. Moreover, the correlation between relationship satisfaction and negative affect (with negative events held constant), was maximized at the point of relationship-judgment discontinuity. Although the findings are complex, they are consistent with the authors' theoretical account and represent an initial attempt to conceptualize the effect of negative life events in light of the recent social judgment literature.

Attribution processes in distressed and nondistressed couples: 4. Self-partner attribution differences.

The importance of the self-other distinction for understanding the relation between attributions and marital satisfaction is examined in two studies. In Study 1, causal attributions for naturally occurring behavior by the self and spouse were investigated. Study 2 examined both causal and responsibility attributions for hypothetical behaviors. In both studies, the attributions of spouses seeking therapy were investigated in relation to those of happily married persons in the community. The results showed that self-other attribution differences varied as a function of marital distress. Nondistressed spouses showed a positive attribution bias by making more benign attributions for partner behavior as opposed to self-behavior, whereas distressed spouses showed a negative attribution bias by making less benign attributions for partner behavior than for self-behavior. These findings suggest that self-attributions may, in part, determine the impact of attributions for spouse behavior on marital satisfaction. The clinical relevance of the results and their implications for research on actor-observer attribution differences are outlined.

Pleasure and pain in doing well, together: an investigation of performance-related affect in close relationships.

In a series of four studies, the self-evaluation maintenance (SEM) model is used to predict peoples' self-reported affective responses to doing better or worse than their partners. Both self-protective reactions to comparison (i.e., those predicted by the original SEM model) and empathic reactions to the partner's response (i.e., those predicted by the extended SEM model) were obtained. In addition, as predicted on the basis of both models, comparisons with romantic partners resulted in a different pattern of self-reported affect than did comparisons with strangers. Unexpectedly, it appeared that empathic effects were minimal or absent among dating partners when comparisons were in areas of high self-relevance.

Negative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study.

Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.

Attributions in marriage: examining the entailment model in dyadic context.

The entailment model of attributions is examined for the first time using a dyadic approach and longitudinal data. In a sample of 229 married partners with children, causal attributions were distinguished empirically from responsibility attributions and, consistent with the entailment model, the effect of causal attributions on conflict was mediated through attributions of responsibility. Only 1 path was influenced by spouse gender. Examination of cross-spouse effects revealed significant effects and provided a better fit than a model with no cross-spouse effects. The importance of including cross-spouse effects in attributional models is discussed.

Dysphoria and marital discord: are dysphoric individuals at risk for marital maladjustment?

The effect of dysphoria on husbands' and wives' later marital adjustment was examined in a sample of 264 white couples about to marry who responded to advertisements. Relationship satisfaction and level of dysphoria were assessed in both spouses prior to marriage, 6 months after marriage, and 18 months after marriage. Premarital dysphoria was associated with later marital dissatisfaction. Husbands' premarital dysphoria, regardless of chronicity, was associated with greater deterioration in both their own and their partners' marital satisfaction. Wives' premarital dysphoria was associated with greater deterioration in marital satisfaction only if it was chronic. Results suggest that premarital dysphoria is associated with subsequent deterioration of marital relationships.

Individual and crossover effects of stress on adjustment in medical student marriages.

High-stress individuals may benefit from social support, although their support providers may be adversely affected via stress crossover effects. Individual and crossover effects of perceived stress within medical student marriages (n = 30) were investigated. Perceived spousal support was positively associated with individuals' own marital and emotional adjustment, attenuating stress effects. With regard to crossover effects, medical students' perceived stress was significantly associated with their spouses' emotional adjustment. Further, medical students' own emotional adjustment fully mediated this crossover effect. Results suggest that the contagion of negative affect may serve as a key mechanism through which stress crossover effects operate in marriage.

Excuses, excuses: accounting for the effects of partner violence on marital satisfaction and stability.

For both theoretical and practical reasons, it is important to understand processes that lead to marital dissatisfaction and dissolution among women who are targets of relationship violence. Because attributional tendencies may often forecast marital behavior and because alcohol use is often seen as providing an excuse for deviant behavior, we examine two potential moderators of the associations between husband violence and wife marital outcomes: wife attributional style and husband problem drinking tendencies. A community sample of married couples (N = 66) completed a comprehensive battery of marital assessments. Results suggested that responsibility attributions moderated the association between husband violence and wives' marital dissatisfaction but exerted a direct effect on wives' disposition toward divorce. Husband problem drinking moderated the impact of husband violence only on wives' disposition toward divorce. As would be expected from an "excuse" model of the associations between violence and marital outcomes, violence had less of an impact on marital satisfaction and divorce ideation when wives attributed responsibility for negative spouse behavior as external to their husbands and when husbands were problem drinkers, respectively.

Maternal and paternal parenting during adolescence: forecasting early adult psychosocial adjustment.

This study investigated the relationship of maternal and paternal parenting behavior (acceptance and firm control) during adolescence to four domains of early adult functioning (internalizing problems, externalizing problems, prosocial competence, and cognitive competence). Twenty-one females and 29 males from intact families, along with their mothers and fathers, participated. Assessments were conducted in adolescence and early adulthood, separated by approximately five and one-half years. Higher levels of maternal firm control during adolescence were associated with more secure early adult romantic attachment and lower levels of educational achievement. There were no main effects for fathers, but paternal parenting behavior interacted with maternal parenting behavior to predict both early adult romantic attachment and delinquency. Clinical implications and directions for future research are discussed.

A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.

Peripheral mononuclear cell preparations are commonly used as proxies for other tissues in studies of the role of gene expression and methylation in human disease. Whether changes in peripheral DNA methylation are associated with changes in peripheral blood or brain gene expression is not clear. In order to test the former hypothesis and determine which genome-wide methylation platform was most suitable for our studies of peripheral blood cells, we compared the results from two commercially available genome-wide methylation arrays with respect to genome-wide gene expression using lymphoblast DNA and RNA from eight individuals at the promoters of 5619 genes. We found that methylation signatures at these gene promoters were significantly correlated with one another across platforms and with genome-wide gene expression, but the extent of that relationship is dependent on choice of platform and degree of methylation. Taken in context with data from other studies, these data demonstrate that peripheral blood cell methylation is associated with gene expression and that further studies to clarify the extent of this relationship, and the relationship between central and peripheral DNA methylation are in order.

Conflict in marraige: implications for working with couples.

The investigation of marital conflict has reached a crossroads. Over 25 years of research on marital conflict behavior yields a relatively clear picture of its topography, but its relevance for changing the marital relationship remains controversial. We can continue to amass observations in a relatively atheoretical manner and hope that patterns capable of guiding clinical activity will emerge, or we can begin creating a unified theoretical framework to indicate new directions for clinical activity and empirical investigation. Before exploring the latter option, this chapter reviews briefly the impact of marital conflict on mental, physical, and family health and what is known about the nature of conflict in marriage. After highlighting some recent theoretically grounded advances, we illustrate how conceptualizing marital conflict behavior as goal directed provides an integrative theoretical framework for treatment, prevention, and marital conflict research.

Assessment of perceptual discrepancy: utility of the Primary Communication Inventory.

The Primary Communication Inventory was factor-analyzed in order to validate the subscales of this instrument. These subscales were derived by Navran (20) on the basis of face validity and were labeled verbal and nonverbal communication subscales. The analysis yielded two factors. However, they could not be labeled verbal and nonverbal. Instead, the factors were interpreted as: (a) the individual's perceptions of own communication ability, and (b) the spouse's perceptions of the individual's communication ability. The scoring of the Primary Communication Inventory was revised and used as a measure of perceptual discrepancy between husbands and wives. Interestingly, discrepancy within the marital dyad was greater for the nondistressed participants than for the distressed participants. The results illustrate the potentially adaptive nature of positive perceptual distortion within the marital dyad and the potential utility for future research of calculating perceptual discrepancy scores for each spouse using the Primary Communication Inventory.