A mechanism-focused approach to the science of behavior change: An introduction to the special issue

The National Institutes of Health (NIH) Science Of Behavior Change initiative (SOBC; https://commonfund.nih.gov/behaviorchange)—supported by the NIH Common Fund (https://commonfund.nih.gov/)—is an explicit effort to address the stymied and siloed behavior change field. As described in this Special Issue, SOBC represents a fundamental change in the way that research on initiation, personalization, and maintenance of behavior change is being conducted and applied. In this editorial, we highlight key contributions of SOBC in these areas

Genetic Influences on the Neural and Physiological Bases of Acute Threat: A Research Domain Criteria (RDoC) Perspective

The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35–50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. © 2015 Wiley Periodicals, Inc

Caregiving and 5-HTTLPR Genotype Predict Adolescent Physiological Stress Reactivity: Confirmatory Tests of Gene × Environment Interactions

A theory-driven confirmatory approach comparing diathesis–stress and differential susceptibility models of Gene × Environment (G × E) interactions was applied to examine whether 5-HTTLPR genotype moderated the effect of early maternal caregiving on autonomic nervous system (ANS) stress reactivity in 113 adolescents aged 13–17 years. Findings supported a differential susceptibility, rather than diathesis–stress, framework. Carriers of one or more 5-HTTLPR short alleles (SS/SL carriers) reporting higher quality caregiving exhibited approach ANS responses to a speech task, whereas those reporting lower quality caregiving exhibited withdrawal ANS responses. Carriers of two 5-HTTLPR long alleles (LL carriers) were unaffected by caregiving. Findings suggest that 5-HTTLPR genotype and early caregiving in interaction are associated with ANS stress reactivity in adolescents in a “for better and for worse” fashion, and they demonstrate the promise of confirmatory methods for testing G × E interactions

Associations between adjustment disorder and hospital-based infections in the Danish population.

OBJECTIVE:There is some evidence that posttraumatic stress disorder (PTSD) is associated with increased risk of infections, and it is unknown whether adjustment disorder is as well. We assessed the association between adjustment disorder and subsequent infections, and assessed additive interaction with sex. METHODS:The study population included a nationwide cohort of all Danish-born residents of Denmark diagnosed with adjustment disorder between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We compared rates of infections requiring inpatient or outpatient hospitalization in the two cohorts. We fit Cox proportional hazards models to compute adjusted hazard ratios (aHR) for the associations between adjustment disorder and 32 types of infections, and calculated interaction contrasts to assess interaction between adjustment disorder and sex. RESULTS:Adjustment disorder was associated with increased rates of infections overall (n = 19,838 infections, aHR = 1.8, 95% confidence interval = 1.8. 1.9), and increased rates of each individual infection type (aHRs for 30 infections ranged from 1.5 to 2.3), adjusting for baseline psychiatric and somatic comorbidities and marital status. For many infection types (e.g., skin infections, pneumonia), interaction contrasts indicated rate differences were greater among men than women, while for two (urinary tract infections and sexually transmitted infections), rate differences were greater for women. CONCLUSIONS:These findings are consistent with studies examining the relationship between psychological stress and infections, and between PTSD and infections. They may be explained by a combination of the triggering of unhealthy behaviors as well as immune responses to stress

Perceived clinician-patient communication in the emergency department and subsequent post-traumatic stress symptoms in patients evaluated for acute coronary syndrome

Objectives: Evaluation for a potentially life-threatening cardiac event in the emergency department (ED) is a stressful experience that can result in symptoms of post-traumatic stress disorder, which are associated with increased risk of morbidity and mortality in patients. No study has tested whether good clinician–patient communication in the ED is associated with better psychological outcomes in these individuals and whether it can mitigate other risk factors for post-traumatic stress symptoms (PSS) such as perception of life threat and vulnerability in the ED. Methods: Data were analysed from 474 participants in the Reactions to Acute Care and Hospitalization (REACH) study, an observational cohort study of ED predictors of medical and psychological outcomes after evaluation for suspected acute coronary syndrome. Participants were recruited from November 2013 to January 2015 at a single-site academic medical centre (New York-Presbyterian-Columbia University Medical Center). Participants reported threat perceptions in the ED and provided information on their perceptions of clinician–patient communication using the Interpersonal Process of Care Survey. PSS were assessed using the Acute Stress Disorder Scale during follow-up. Results: 474 subjects were enrolled in the study. Median length of follow-up was 3 days after ED presentation, range 0–30 days, 80% within 8 days. Perceptions of good clinician–patient communication in the ED were associated with lower PSS, whereas increased threat perception was associated with higher PSS. A significant interaction between clinician–patient communication and threat perception on PSS suggested that patients with higher threat perception benefited most from good clinician–patient communication. Conclusion: Our study found an association between good clinician–patient communication in the ED during evaluation of potentially life-threatening cardiac events and decreased subsequent post-traumatic stress reactions. This association is particularly marked for patients who perceive the greatest degree of life threat and vulnerability during evaluation

Dimensional structure and correlates of posttraumatic stress symptoms following suspected acute coronary syndrome

Background Posttraumatic stress disorder (PTSD) is a heterogeneous construct, and some have suggested that PTSD triggered by acute coronary syndrome (ACS) may differ from PTSD due to prototypical traumas. Methods We conducted the first examination of the latent structure of PTSD symptoms after suspected ACS in 399 adults in the REactions to Acute Care and Hospitalization (REACH) study, an observational cohort study of patients recruited from the emergency department during evaluation for ACS. Using confirmatory factor analysis, we compared the 4-factor dysphoria, 4-factor numbing, and 5-factor dysphoric arousal models of PTSD. Results Although all models fit well, the dysphoria model was selected as the best-fitting model. Further, there was measurement invariance of the dysphoria model by sex. PTSD dimensions evidenced differential associations with indicators of threat perception during ACS evaluation and adherence to cardioprotective medication. Limitations One limitation of this investigation is the use of self-report measures. In addition, only one-third of the sample was diagnosed with ACS at discharge; the remaining participants received diagnoses such as chest pain without a cardiac diagnosis, another symptom/disease process (e.g., hypertensive chronic kidney disease), or another cardiac disease. Conclusions Findings suggest that suspected ACS-related PTSD symptoms are best-represented by a 4-factor structure distinguishing between specific (e.g., re-experiencing) and non-specific (dysphoria) symptoms of PTSD that has received support in the broader PTSD literature

Association of the rs2242446 polymorphism in the norepinephrine transporter gene SLC6A2 and anxious arousal symptoms of posttraumatic stress disorder

To the Editor: Recently, we found that greater norepinephrine transporter (NET) availability in the locus ceruleus of trauma survivors with posttraumatic stress disorder (PTSD) was associated with increased severity of anxious arousal (ie, hypervigilance and exaggerated startle) symptoms, but not any of the other empirically derived symptom clusters that characterize this disorder.1 This finding suggests that greater NET availability in the locus ceruleus may serve a compensatory function of clearing elevated synaptic norepinephrine and maintaining anxious arousal symptoms in persons with PTSD

Association of the rs2242446 polymorphism in the norepinephrine transporter gene SLC6A2 and anxious arousal symptoms of posttraumatic stress disorder

To the Editor: Recently, we found that greater norepinephrine transporter (NET) availability in the locus ceruleus of trauma survivors with posttraumatic stress disorder (PTSD) was associated with increased severity of anxious arousal (ie, hypervigilance and exaggerated startle) symptoms, but not any of the other empirically derived symptom clusters that characterize this disorder.1 This finding suggests that greater NET availability in the locus ceruleus may serve a compensatory function of clearing elevated synaptic norepinephrine and maintaining anxious arousal symptoms in persons with PTSD

Posttraumatic stress disorder and accelerated aging: PTSD and leukocyte telomere length in a sample of civilian women.

BACKGROUND: Studies in male combat veterans have suggested posttraumatic stress disorder (PTSD) is associated with shorter telomere length (TL). We examined the cross-sectional association of PTSD with TL in women exposed to traumas common in civilian life. METHODS: Data are from a substudy of the Nurses' Health Study II (N = 116). PTSD and subclinical PTSD were assessed in trauma-exposed women using diagnostic interviews. An array of health behaviors and conditions were assessed. DNA was extracted from peripheral blood leukocytes (collected 1996-1999). Telomere repeat copy number to single gene copy number (T/S) was determined by quantitative real-time PCR telomere assay. We used linear regression models to assess associations and examine whether a range of important health behaviors (e.g., cigarette smoking) and medical conditions (e.g., hypertension) previously associated with TL might explain a PTSD-TL association. We further examined whether type of trauma exposure (e.g., interpersonal violence) was associated with TL and whether trauma type might explain a PTSD-TL association. RESULTS: Relative to not having PTSD, women with a PTSD diagnosis had shorter log-transformed TL (β = -.112, 95% confidence interval (CI) = -0.196, -0.028). Adjustment for health behaviors and medical conditions did not attenuate this association. Trauma type was not associated with TL and did not account for the association of PTSD with TL. CONCLUSIONS: Our results add to growing evidence that PTSD may be associated with more rapid cellular aging as measured by telomere erosion. Moreover, the association could not be explained by health behaviors and medical conditions assessed in this study, nor by type of trauma exposure

Effects of Concurrent Depressive Symptoms and Perceived Stress on Cardiovascular Risk in Low‐ and High‐Income Participants: ...

Background: Psychosocial risk for cardiovascular disease (CVD) may be especially deleterious in persons with low socioeconomic status. Most work has focused on psychosocial factors individually, but emerging research suggests that the confluence of psychosocial risk may be particularly harmful. Using data from the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study, we examined associations among depressive symptoms and stress, alone and in combination, and incident CVD and all‐cause mortality as a function of socioeconomic status. Methods and Results At baseline, 22 658 participants without a history of CVD (58.8% female, 41.7% black, mean age 63.9±9.3 years) reported on depressive symptoms, stress, annual household income, and education. Participants were classified into 1 of 3 psychosocial risk groups at baseline: (1) neither depressive symptoms nor stress, (2) either depressive symptoms or stress, or (3) both depressive symptoms and stress. Cox proportional hazards models were used to predict physician‐adjudicated incident total CVD events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and all‐cause mortality over a median of 7.0 years (interquartile range 5.4–8.3 years) of follow‐up. In fully adjusted models, participants with both depressive symptoms and stress had the greatest elevation in risk of developing total CVD (hazard ratio 1.48, 95% CI 1.21–1.81) and all‐cause mortality (hazard ratio 1.33, 95% CI 1.13–1.56) but only for those with low income (< $35 000) and not high (≥$35 000) income. This pattern of results was not observed in models stratified by education. Conclusions Findings suggest that screening for a combination of elevated depressive symptoms and stress in low‐income persons may help identify those at increased risk of incident CVD and mortality