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PubMed2002

Randomized clinical trials, developmental theory, and antisocial youth: guidelines for research.

The design of effective interventions for antisocial adolescents has been greatly influenced by research-based developmental theories. However, randomized clinical trials (RCTs) demonstrating effectiveness of these treatments have contributed minimally to alterations and refinements of these theories. In this article, nine guidelines for research that may enhance the contributions of RCTs to developmental theory are proposed: (1) use mediational analyses to test and refine theories of change; (2) use moderator analyses to test differential pathways to change; (3) assess change processes separately for different types of antisocial behavior; (4) use constructive and dismantling designs to isolate effects of intervention components on targeted mediators and outcomes; (5) assess the time-sensitive nature of change mechanisms with theoretically relevant spacing of multiple assessments and long-term follow-ups; (6) expand the nomological net of developmental theories by assessing intervention effects on nontargeted constructs; (7) use RCTs to disentangle direction of effects questions in developmental theories; (8) conduct secondary analyses of RCTs to assess extra-treatment influences on antisocial behavior; and (9) assess the generalizability of mediator and moderator effects. Use of these guidelines may promote a recursive and iterative relationship between RCTs and theory building. Improved developmental theories may yield more effective interventions, and theory-testing interventions may engender more comprehensive and better informed theories.

Antisocial Personality Disorder↗

PubMed2003

Childhood sexual abuse and sexual transmission risk behaviour among HIV-positive men who have sex with men.

Previous studies have indicated an association between childhood sexual abuse (CSA) and adult sexual risk behaviour among women and among men who have sex with men (MSM). However, no studies to date have tested the hypothesis that a history of CSA predicts sexual behaviour carrying risk of transmission of HIV to others, i.e. in a known HIV-positive cohort. The present study tested this hypothesis among a sample of 456 HIV-positive MSM recruited from community venues in New York and San Francisco. CSA history was found to be significantly associated with past (in the last 90 days) unprotected anal sex acts, both insertive (33% versus 20%, p < 0.05) and receptive (43% versus 27%, p < 0.02), with partners of HIV-negative or unknown serostatus. Further, several potential mediators of this effect were tested, and three found to be predicted by CSA history. Each of these potential mediators was associated with sexual risk behaviour, but differentially: anxiety and hostility were significantly associated with insertive acts, while anxiety, hostility and suicidality were associated with receptive acts. Mediation analyses supported the hypothesis that these factors significantly (albeit partially) accounted for the association of CSA with receptive anal intercourse. Nonsignificant mediation effects were found for insertive sex, suggesting the operation of unmeasured mediating variables. These results highlight the importance of mental health services for individuals who have been sexually abused, both for personal and for public health benefit, and also indicate a need for further research into mediators of CSA effects on transmission-related behaviour.

Adult↗

PubMed2000

Alcohol treatment, changes in coping skills, self-efficacy, and levels of alcohol use and related problems 1 year following treatment initiation.

The relationships among alcohol treatment, coping skills, and self-efficacy in predicting alcohol use and related consequences following treatment initiation were investigated. The participants were 77 men and 65 women who were entering either inpatient or outpatient alcohol treatment. The analyses confirmed predictions that treatment, coping skills, and self-efficacy each contributed significantly to the prediction of 12-month alcohol consumption beyond the variance accounted for by participant control variables. Only self-efficacy explained significant additional variance in the consequences outcome. Mediation analyses of the alcohol consumption variables suggested that treatment effects were not mediated by either coping skills or self-efficacy and that the effects of coping skills were not mediated by self-efficacy. The findings are interpreted as providing partial support for social learning theory approaches. Suggestions for future research are discussed.

Adaptation, Psychological↗

PubMed2004

The impact of anti-tobacco industry prevention messages in tobacco producing regions: evidence from the US truth campaign.

BACKGROUND: Adolescents who live in tobacco producing regions may not respond favourably to anti-industry ads. OBJECTIVE: To examine whether state level involvement in tobacco production appears to limit the effectiveness of anti-industry ads to prevent tobacco use among adolescents in the USA. DESIGN: Time trend analyses were done using repeated cross sectional data from six waves of the Legacy Media Tracking Survey, which were collected between 1999 and 2003. SETTING AND PARTICIPANTS: 28,307 adolescents, ages 12-17 years, were classified as living in: tobacco producing states (TPS) (n = 1929); non-tobacco producing states (non-TPS) with low tobacco control funding comparable to TPS (n = 5323); non-TPS with relatively high funding (n = 15,076); and non-TPS with established anti-industry ad campaigns (n = 5979). MAIN OUTCOME MEASURES: Reactions to anti-industry ads; strength of anti-industry attitudes/beliefs; changes in anti-industry attitudes/beliefs over time. RESULTS: Ad reactions did not differ by state type. Multivariate adjusted time trend analyses indicated significant, comparable increases in anti-industry attitudes/beliefs since the onset of the truth campaign, in both TPS and non-TPS. Mediation analyses indicated that these increases were due, in part, to campaign exposure. CONCLUSIONS: Adolescents who live in tobacco producing regions appear to be as responsive to anti-industry ads as their counterparts in non-tobacco producing regions. This study provides further evidence for the effectiveness of such ads.

Adolescent↗

PubMed2025

Mediators of the Association Between a Parent's Experience of Trauma and Their Children's Well-Being: A Systematic Review.

At present, our understanding of trauma's complexity is underdeveloped, particularly with regard to intergenerational effects. In this paper, we review peer-reviewed literature on parental trauma and child well-being, focusing on mediating factors. We conducted a global systematic review of longitudinal, observational studies assessing mediators between a parent's traumatic exposure and their children's well-being. The primary outcome of the review was quantitative measures of child well-being (physical and psycho-social) assessed when the child was 18 years or under. We considered the following experiences as trauma exposures: intimate partner violence, rape, sexual assault, victimization during violent crime, childhood abuse, and exposure to direct, immediate threats to personal survival during war, political unrest, natural disasters, and sudden, critical injury/illness. Thirty-two studies met our inclusion criteria. The two most common mediator categories were caregiver mental health (n = 13) and parenting behavior (n = 10). Other studies measured aspects of the parent-child relationship (n = 9), maternal stress factors (n = 5), parental physical health (n = 2), and child-level factors (n = 6) as mediators. Almost all included studies (n = 28) detected a mediation effect. The majority of studies (n = 21) cited robust theoretical frameworks to support their mediator and outcome choices. Studies varied in quality, but most used appropriate, formal mediation analyses. Several study designs could be enhanced by methods to improve precision and reduce bias. Currently, there is little consistency in how similar constructs are measured between mediation studies. We did not locate any studies in low-income countries, and few studies examined aspects of family dynamics, physical health, environmental characteristics, or paternal factors.

Humans↗

PubMed2006

Physical activity and depressive symptoms in cardiac rehabilitation: long-term effects of a self-management intervention.

Long-term effects of a self-management intervention on physical activity and depressive symptoms were studied in 198 men and women after cardiac rehabilitation in Germany. Participants were randomly assigned to either an intervention group or a standard-care control group. The intervention group received brief self-regulatory skills training that focused on exercise planning strategies. Four and 12 months later, physical exercise levels were half a standard deviation higher in the intervention group. Depressive symptoms 12 months after discharge were almost half a standard deviation lower in the intervention group than in the control group. Mediation analyses were performed to study the potential mechanism that accounted for the reduction in depression. Perceived attainment of exercise goals, but not physical exercise itself, emerged as a mediator between the intervention and the reduction of depressive symptoms. As such attainment of personal goals appears to be of particular importance for lowering depressive symptoms during health-behavior change. Thus, self-management strategies to help patients attain their goals should be part of rehabilitation programs.

Adult↗

PubMed2000

Heparin inhibits eicosanoid metabolism and hyperventilation-induced bronchoconstriction in dogs.

Inhalation of heparin, an anticoagulant, attenuates exercise- induced asthma (EIA) in human subjects. The purpose of this study was to determine if heparin inhibits hyperventilation-induced bronchoconstriction (HIB) in a canine model of EIA, and if its mode of action involves the inhibition of eicosanoid mediator production and release. We used a wedged bronchoscope technique to measure baseline peripheral airway resistance (Rp). We then performed either a 2-min or 5-min dry air challenge (DAC) by temporarily increasing from 200 to 2,000 ml/min the flow of 5% CO(2) in air used to ventilate a wedged sublobar segment. We compared HIB before and 60 min after aerosol treatment with either bacteriostatic water (BW) or heparin. We found that (1) heparin had no effect on baseline Rp, (2) BW did not alter the response to DAC, and (3) heparin reduced HIB by approximately 50-60%. On the basis of bronchoalveolar lavage fluid (BALF) cell analysis, heparin and BW caused acute infiltration of macrophages and eosinophils, and heparin increased the number of erythrocytes recovered immediately after DAC. Despite these acute inflammatory effects initiated prior to DAC, BALF mediator analyses revealed that pretreatment with heparin either attenuated or abolished hyperventilation-induced leukotriene, prostaglandin, and thromboxane release. Thus, our data provide direct evidence that inhaled heparin inhibits eicosanoid mediator production and release caused by hyperventilation with dry air, and significantly attenuates HIB.

Administration, Inhalation↗

PubMed2003

Psychological risk factors for HIV pathogenesis: mediation by the autonomic nervous system.

BACKGROUND: Epidemiologic studies have identified psychological risk factors for specific physical diseases, but the biological mechanisms mediating these relationships remain poorly defined. METHODS: Social inhibition and autonomic nervous system (ANS) activity were assessed on multiple occasions in 54 gay men with asymptomatic human immunodeficiency virus (HIV) infection. Following baseline ANS assessment, plasma HIV-1 viral load and CD4+ T cell levels were monitored for 12-18 months to assess relationships between ANS activity and HIV pathogenesis. RESULTS: We confirmed the previously reported relationship between socially inhibited temperament and vulnerability to viral pathology. Plasma viral load set-point was elevated eight-fold in socially inhibited individuals, and these individuals showed poorer virologic and immunologic response to initiation of highly active antiretroviral therapy (HAART). Effects were independent of duration of infection, HAART regimen, demographic characteristics, and health-relevant behavior. Neurophysiologic assessments documented elevated ANS activity in socially inhibited individuals, and mediational analyses showed that such differences could account for 64%-92% of the covariance between social inhibition and virologic parameters. CONCLUSIONS: These data provide the first clinical evidence that differential neural activity mediates relationships between psychological risk factors and infectious disease pathogenesis. Such findings also suggest novel targets for adjunctive therapy in long-term control of HIV-1 disease.

Adult↗

PubMed2006

Daily occupational stressors and marital behavior.

This study examined daily fluctuations in marital behavior (anger and withdrawal) as a function of same-day job stressors, using hierarchical linear modeling (HLM). Forty-three couples provided daily diary reports of their workload and negative social interactions at work on 5 consecutive days. Within-subject analyses demonstrate that husbands and wives reported greater marital anger and withdrawal following negative social interactions at work, and wives reported greater marital anger and withdrawal following days of heavy workload. Mediation analyses provide support for the negative mood spillover hypothesis (e.g., workload no longer predicted wives' marital anger when controlling for negative mood). Between-subjects analyses suggest that spouses in high-conflict families may be especially vulnerable to the effects of job stressors on marital interaction.

Adult↗

PubMed2025

Glutaryl-CoA dehydrogenase (GCDH) enhances renal malignancy risk via modulating glutarylcarnitine levels.

BACKGROUND: Crotonylation, a recently identified lysine acylation, plays a critical role in post-translational modifications [1]. It has been implicated in tumorigenesis by modulating metabolic reprogramming [2], DNA repair, immune evasion [3], and oncogenic signaling pathways, including PKA-FAK-AKT and androgen receptor signaling [4]. The specific role of crotonylation in renal malignancy (RM) remains poorly understood, especially in interaction with gene expression and metabolic pathway interactions. METHODS: This study integrates genome-wide association study (GWAS) summary statistics for RM from the FinnGen database, data on crotonylation-associated gene expression obtained from the eQTLGen consortium, and metabolite GWAS data obtained from the GWAS Catalog. A combined two-sample Mendelian randomization (MR), summary data-based Mendelian randomization (SMR), and mediation analyses were performed to investigate the causal link between Glutaryl-CoA dehydrogenase (GCDH) and RM, with a specific focus on glutarylcarnitine metabolism. RESULTS: MR analysis demonstrated a significant association; increased expression of GCDH is likely to increase the risk of RM (OR = 1.25, P = 0.0045). Mediation analysis revealed that elevated GCDH expression significantly reduced glutarylcarnitine (C5-DC) levels, which in turn was inversely associated with RM risk. A three-step MR-based mediation confirmed a significant mediating effect of glutarylcarnitine (β₁₂ = 0.0680, P = 0.002), with 30.25% of the total effect attributable to it. The robustness of these findings was further demonstrated by sensitivity analyses and SMR results. CONCLUSION: This study represents the first evidence that GCDH might exert an indirect pro-RM effect via the downregulation of glutarylcarnitine, thus providing new insights into tumor metabolic pathways and positioning glutarylcarnitine as a potentially diagnostic biomarker and therapeutic target for RM.

GCDH↗

PubMed2026

Social disconnection integrates genetic and proteomic risks in suicidal ideation and depression.

Suicidal ideation (SI) and major depressive disorder (MDD) are complex psychiatric conditions arising from the interplay of genetic liability, molecular processes, and psychosocial factors. While these dimensions have been extensively studied in isolation, their joint contribution to SI and MDD remains unclear. This study integrates multi-modal data to elucidate these synergistic effects and develop robust models for individual-level risk stratification. Leveraging longitudinal multi-modal data from 13,085 UK Biobank participants, we integrated genomic, proteomic, and social connection profiles. We developed interpretable risk scores using a rigorous supervised machine learning framework encompassing diverse linear and ensemble classifiers. Permutation importance was employed to quantify feature contributions and derive transparent, weighted risk metrics across diverse classifiers. These scores were validated through association, interaction, and mediation analyses. Social connection-based risk scores significantly differentiated cases and controls across the two suicidal ideation phenotypes at 2017 and 2023 with cross-sectional analyses (AUCs: 0.70 - 0.73), outperforming proteomic-only models. Functional dimensions of social connection emerged as the most informative predictors. Longitudinal analyses revealed that social risk scores at baseline predicted suicidal ideation onset six years later, independent of demographic covariates. Interaction analyses demonstrated that polygenic risk for suicide attempt significantly interacted with both social and proteomic risk features in relation to depression. Structural equation models further confirmed that social disconnection acts as a key mediator linking genetic predisposition to MDD and SI. Social disconnection is a critical risk factor mediating the impact of genetic vulnerability on psychiatric outcomes. Integrating social, genetic, and molecular data supports a multilevel framework for risk stratification and highlights the potential of socially oriented interventions to mitigate biological risk.

Humans↗

PubMed2002

Positive emotions trigger upward spirals toward emotional well-being.

The broaden-and-build theory of positive emotions predicts that positive emotions broaden the scopes of attention and cognition, and, by consequence, initiate upward spirals toward increasing emotional well-being. The present study assessed this prediction by testing whether positive affect and broad-minded coping reciprocally and prospectively predict one another. One hundred thirty-eight college students completed self-report measures of affect and coping at two assessment periods 5 weeks apart. As hypothesized, regression analyses showed that initial positive affect, but not negative affect, predicted improved broad-minded coping, and initial broad-minded coping predicted increased positive affect, but not reductions in negative affect. Further mediational analyses showed that positive affect and broad-minded coping serially enhanced one another. These findings provide prospective evidence to support the prediction that positive emotions initiate upward spirals toward enhanced emotional wellbeing. Implications for clinical practice and health promotion are discussed.

Adaptation, Psychological↗

PubMedDate not supplied

Unpacking immigration in youths' academic and occupational pathways.

This study sought to unpack how immigration is associated with youths' educational choices during the transition to college and adulthood. Surveys and school records were collected on 789 youth (ages 18-25) with Asian Pacific, Latino, African/Afro-Caribbean, and European backgrounds. The results indicated generational differences in educational choices, such that children of immigrants chose courses of study with higher math and science content than that of their peers with U.S.-born parents. Mediation analyses indicated that children of immigrants reported higher social and economic aspirations than did their peers, and their economic aspirations accounted for part of the generational difference in educational choices. Generational differences in educational choices were also mediated by verbal achievement test scores and perceived English skills.

Achievement↗

PubMed2002

Self-respect and pro-relationship behavior in marital relationships.

This work advances an interdependence theoretic analysis of the role of self-respect in ongoing close relationships. Self-respect is defined as the tendency to perceive the self as a principled person who is worthy of honor and high regard and is argued to rest on moral integrity. Consistent with predictions, results from a study of marital relationships revealed that individual self-respect is positively associated with both the individual's and the partner's pro-relationship behavior (accommodation, forgiveness, conciliation). Mediation analyses revealed that self-respect not only exhibits direct associations with each person's behavior, but also exhibits indirect associations with each person's behavior, via the impact of each person's actions on reciprocal pro-relationship behavior from the partner. Mediation was more reliably observed for the association of self-respect with partner behavior than for the association with individual behavior. Both individual pro-relationship behavior and partner pro-relationship behavior are positively associated with couple well-being, which in turn is positively associated with personal well-being (life satisfaction, physical health, psychological adjustment). These associations were evident in both within-participant and across-partner analyses and for both self-report and interaction-based measures of behavior. Self-respect reliably accounts for unique variance beyond variance attributable to self-esteem.

Adaptation, Psychological↗

PubMed2006

Mediation of a middle school skin cancer prevention program.

This study tested potential mediators of a school-based skin cancer prevention intervention for middle school children (6th-8th grades; N = 1,788). Ten variables were tested on 4 criteria to establish mediation, including (a) intervention related to outcome, (b) intervention related to mediators, (c) mediators related to outcome, and (d) mediated effect statistically significant. Sun-safe behaviors (e.g., sunscreen use) and potential mediators were measured with a self-report questionnaire. All criteria were met for Barriers--Sunscreen, Perceived Self-Efficacy, and Knowledge when the mediators were tested separately. In multiple mediator analyses, barriers to sunscreen use and self-efficacy satisfied Criteria 1-3 but were not statistically significant (Criterion 4). Barriers to sunscreen use, perceived self-efficacy for sun-safe behavior, and knowledge may serve as mediators.

Adolescent↗

PubMed1997

Self-events and other-events: temporal dating and event memory.

A diary methodology was used to assess factors related to temporal dating and cued recall of real-world events. In one diary, participants kept a record of unique personal autobiographical events. In a second diary, participants recorded unique events from the life of a friend or relation. At the time each event was recorded, participants rated the event's pleasantness, person typicality, and degree of initial mental involvement in the event. At the end of the academic quarter, participants provided a recall rating, a rehearsal rating, a date estimate, and a report of the strategy used to estimate the date for each event. Results of regression analyses indicated that both self-events and other-events were characterized by superior memory for person-atypical events. Furthermore, there was a positivity bias in recall for self-events, but there was a negativity bias in recall for other-events. Mediational analyses indicated that the self-event positivity bias was due to enhanced mental involvement when the events occurred, whereas the other-event negativity bias was due to subsequent event rehearsal. The date estimation results indicated that self-event dating was more accurate and evinced less telescoping than other-event dating. Furthermore, the accuracy of date estimates was substantially mediated by event memory. However, mediational differences between self-events and other-events did not emerge. The theoretical implications of these results are discussed.

Adult↗

PubMedDate not supplied

Personality factors in the explanation of sex differences in pain catastrophizing and response to experimental pain.

OBJECTIVE: To examine the effects of personality and pain catastrophizing upon pain tolerance and pain ratings and to examine the impact of an experimental pain induction on subsequent ratings of catastrophizing. METHOD: Two hundred nineteen college students participated in a cold pressor task. Sex-differentiating personality constructs were measured by the Extended Personal Attributes Questionnaire. The Pain Catastrophizing Scale was given before and after the cold pressor task. RESULTS: A path-analytic model fit the data well and permitted tests of explanatory relationships. Mediational analyses demonstrated that sex differences in catastrophizing were explained by the Personal Attributes Questionnaire Masculinity-Femininity and Verbal Passive-Aggressiveness scales. Pain tolerance and pain ratings differed significantly between men and women, but Masculinity-Femininity partially mediated those sex-pain relationships. Additionally, higher pain ratings and lower pain tolerance were independently associated with increased catastrophizing after the cold pressor task. CONCLUSIONS: The results suggest that sex differences in catastrophizing and pain responsivity are partially accounted for by the dispositional tendency to describe oneself as emotionally vulnerable. The findings also suggest that pain catastrophizing may be situational as well as dispositional.

Adolescent↗

PubMed2001

Physician-based activity counseling: intervention effects on mediators of motivational readiness for physical activity.

In theory-based interventions for behavior change, there is a need to examine the effects of interventions on the underlying theoretical constructs and the mediating role of such constructs. These two questions are addressed in the Physically Active for Life study, a randomized trial of physician-based exercise counseling for older adults. Three hundred fifty-five patients participated (intervention n = 181, control n = 174; mean age = 65.6 years). The underlying theories used were the Transtheoretical Model, Social Cognitive Theory and the constructs of decisional balance (benefits and barriers), self-efficacy, and behavioral and cognitive processes of change. Motivational readiness for physical activity and related constructs were assessed at baseline, 6 weeks, and 8 months. Linear or logistic mixed effects models were used to examine intervention effects on the constructs, and logistic mixed effects models were used for mediator analyses. At 6 weeks, the intervention had significant effects on decisional balance, self-efficacy, and behavioral processes, but these effects were not maintained at 8 months. At 6 weeks, only decisional balance and behavioral processes were identified as mediators of motivational readiness outcomes. Results suggest that interventions of greater intensity and duration may be needed for sustained changes in mediators and motivational readiness for physical activity among older adults.

Aged↗